References on the Administration of Nitric Oxide Synthase Inhibitors Using
ALZET^® Osmotic Pumps

1. 1400W

P7221 Perez-Asenio,F.J., Hurtado,O., Burguete,M.C., Moro,M.A., Salom,J.B., Lizasoain,I., Torregrosa,G., Leza,J.C., Alborch,E., Castillo,J., Knowles,R.G., Lorenzo,P. Inhibition of iNOS activity by 1400W decreases glutamate release and ameliorates stroke outcome after experimental ischemia. NEUROBIOLOGY OF DISEASE 2005; 18(-2-):375-384. >>> 1400W; IP; Rat; 2-72 hours; Controls received mp w/ saline or no treatment.

P6534 Hu,D.E., Dyke,S.O.M., Moore,A.M., Thomsen,L.L., Brindle,K.M. Tumor cell-derived nitric oxide is involved in the immune-rejection of an immunogenic murine lymphoma. Cancer Research 2004; 64(-1-):152-161. >>> 1400W; PBS; SC; Mice; 2001; ; Controls received mp w/ vehicle; enzyme inhibitor (iNOS); cancer (lymphoma).

P5175 Sharp,B.R., Jones,S.P., Rimmer,D.M., Lefer,D.J. Differential response to myocardial reperfusion injury in eNOS-deficient mice. American Journal of Physiology-Heart and Circulatory Physiology 2002; 282(--):H2422-H2426. >>> 1400W; IP; Mice (knockout); ; Cardiovascular; enzyme inhibitor; 1400W is an inducible nitric oxide synthase (iNOS) inhibitor.

P5028 Koarai,A., Ichinose,M., Sugiura,H., Yamagata,S., Hattori,T., Shirato,K. Allergic airway hyperresponsiveness and eosinophil infiltration is reduced by a selective iNOS inhibitor, 1400W, in mice. Pulmonary Pharmacology&Therapeutics 2000; 13(--):267-275. >>> 1400W; Saline; SC; mice; 1003D; 26 hours; Controls received mp w/ vehicle; immunology; 1400 W is a selective inducible Nitric Oxide Synthase (iNOS) inhibitor; asthma.

P4279 Rudd,M.A., Trolliet,M., Hope,S., Scribner,A.W., Daumerie,G., Toolan,G., Cloutier,T., Loscalzo,J. Salt-induced hypertension in Dahl salt-resistant and salt-sensitive rats with NOS II inhibition. Am.J.Physiol.(Heart Circ.Physiol.46) 1999; 277(--):H732-H739. >>> AMT; 1400W; Ethylisourea, S-; Rat; 12 days; Cardiovascular; agents are NOS II inhibitors; AMT is 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine; S-ethylisourea is also known as EIT; enzyme inhibitors; nitric oxide synthase inhibitor;.

P3742 Thomsen,L.L., Scott,J.M.J., Topley,P., Knowles,R.G., Keerie,A.-J., Frend,A.J. Selective inhibition of inducible nitric oxide synthase inhibits tumor growth in vivo: studies with 1400W, a novel inhibitor. Cancer Res. 1997; 57(--):3300-3304. >>> 1400W; Water, sterile; SC; mice; 2002; 6, 12, 13 days; controls received mp w/ vehicle; functionality of mp verified by measurement of 1400W in plasma and tumor samples; stress/adverse reaction: unexpected symptoms in 2 mice in high dose group (12 mg/kg/h), not clear if compound toxicity or bacterial infection (see pg. 3303); cancer; 1400W is N-(3-(aminomethyl)benzyl)acetamidine, a NO synthase inhibitor.

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2. L-NAME

P8361 Gangula,P.R.R., Maner,W.L., Micci,M.A., Garfield,R.E., Pasricha,P.J. Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. American Journal of Physiology-Gastrointestinal and Liver Physiology 2007; 292(-3-):G725-G733. >>> L-NAME; SC; Rat; 2ML1; 4 days; Replacement therapy (STZ-induced diabetes mellitus; enzyme inhibitor (Nitric oxide synthase); animal info (male, female, Sprague-Dawley, 7 wks old).

P8301 Badn,W., Hegardt,P., Fellert,M.A., Darabi,A., Esbjoernsson,M., Smith,K.E., Janelidze,S., Salford,L.G., Visse,E., Siesjoe,P. Inhibition of inducible nitric oxide synthase enhances anti-tumour immune responses in rats immunized with IFN-gamma-secreting glioma cells. SCANDINAVIAN JOURNAL OF IMMUNOLOGY 2007; 65(-3-):289-297. >>> L-NAME; L-NIL; Saline; IP; Rat; 2001; 1 week; 14, 28 days; Controls received mp w/ vehicle; dose-response (fig. 3); comparison of IP injections vs. mp; enzyme inhibitor (Nitric oxide synthase, iNOS); cancer (glioma); L-NIL is L-N6- (1-iminsethyl) -L-lysine.

P8327 Schwenke,D.O., Pearson,J.T., Mori,H., Shirai,M. Does central nitric oxide elicit pulmonary hypertension in conscious rats?. RESPIRATORY PHYSIOLOGY&NEUROBIOLOGY 2006; 153(-3-):250-260. >>> L-NAME; SIN-1; CSF, artificial; CSF/CNS; Rat; 2004; 3 weeks; Controls received mp w/ vehicle; enzyme inhibitor (NO synthase); cardiovascular; animal info (male, Sprague-Dawley, 200-320 grams, 8 weeks old); Evans blue dye used to confirm correct cannula placement; SIN-1 is 2-[4-morpholinyl]-sydnonimine-hydrochloride.

P7889 Coates,B.J., Broderick,T.L., Batia,L.M., Standley,C.A. MgSO4 prevents left ventricular dysfunction in an animal model of preeclampsia. American Journal of Obstetrics and Gynecology 2006; 195(-5-):1398-1403. >>> L-NAME; magnesium sulfate; Saline; SC; Rat (pregnant); 2ML1; 4 days; Controls received mp w/ vehicle; cardiovascular; animal info (female, Sprague-Dawley, 150-175g.); "Infusion of L-NAME in pregnant rats represent an excellent animal model suitable for the study of cardiovascular dysfunction in preeclampsia." (pg. 1401).

P7747 Schwenke,D.O., Pearson,J.T., Kangawa,K., Shirai,M. Does central nitric oxide chronically modulate the acute hypoxic ventilatory response in conscious rats?. ACTA PHYSIOLOGICA 2006; 186(-4-):309-318. >>> L-NAME; sydnonimine-hydrochloride, 3-[4-morpholinyl]-; CSF, artificial; CSF/CNS; Rat; 2004; 3 weeks; Controls received mp w/ vehicle; no stress (see pg. 312); enzyme inhibitor (no synthase); post op. care (viccillin); animal info (male, Sprague-Dawley, 8 wk. old, 200-320g.); correct catheter positioning confirmed post mortem w/ Evans blue dye.

P8215 Aikawa,K., Chichester,P., Whitbeck,C., Levin,R.M. Effect of nitric oxide synthase inhibition on changes induced by estradiol in bladders from ovariectomized rabbits. UROLOGIA INTERNATIONALIS 2005; 75(-2-):133-138. >>> L-NAME; Saline; SC; Rabbit; 4 weeks; Controls received sham OVX w/ no mp; enzyme inhibitor (NO synthase); animal info (female, New Zealand White, 3.5-4.0 kg.).

P7299 Takei,H., Yamamoto,M., Kase,Y., Takeda,S. The effect of herbal medicine Toki-shakuyaku-san on blood pressure in an Nw-nitro-L-arginine methyl ester-induced pre-eclampsia rat model during pregnancy and the postpartum period. JOURNAL OF PHARMACOLOGICAL SCIENCES 2005; 98(-3-):255-262. >>> L-NAME; SC; Rat (pregnant); 2ML2; 2 weeks; Controls received mp w/ saline; enzyme inhibitor (NO synthase); cardiovascular.

P7204 Pfosser,A., Thalgott,M., Buettner,K., Brouet,A., Feron,O., Boekstegers,P., Kupatt,C. Liposomal Hsp90 cDNA induces neovascularization via nitric oxide in chronic ischemia. Cardiovascular Research 2005; 65(-3-):728-736. >>> Geldanamycin; L-NAME; SC; Rabbit; 25, 28 days; Enzyme inhibitor (Hsp90, NO synthase).

P7179 Jacobi,J., Sydow,K., von Degenfeld,G., Zhang,Y., Dayoub,H., Wang,B.Y., Patterson,A.J., Kimoto,M., Blau,H.M., Cooke,J.P. Overexpression of dimethylarginine dimethylaminohydrolase reduces tissue asymmetric dimethylarginine levels and enhances angiogenesis. Circulation 2005; 111(-11-):1431-1438. >>> L-NAME; dimethylarginine, asymmetric; PBS; SC; IP; Mice; mice (transgenic); 2002; 2004; 2, 3 weeks; Controls received mp w/ vehicle; enzyme inhibitor (nitric oxide synthase); cardiovascular; ischemia (hindlimb).

P6953 Thaete,L.G., Kushner,D.M., Dewey,E.R., Neerhof,M.G. Endothelin and the regulation of uteroplacental perfusion in nitric oxide synthase inhibition-induced fetal growth restriction. PLACENTA 2005; 26(-2-3-):242-250. >>> L-NAME; A-127722; Saline; ethyl alcohol; NaOH; water; propylene glycol; SC; Rat (pregnant); 2ML1; 1,4,7 days; Functionality of mp verified by residual volume; stability verified by prior experiment (24 days); multiple pumps per animal (2); drugs infused in separate pumps; A-127722 (ETA receptor antagonist) was dissolved in 20% alcohol, 40% PG and 0.04 M of NaOH.

P7049 Bourraindeloup,M., Adamy,C., Candiani,G., Cailleret,M., Bourin,M.C., Badoual,T., Su,J.B., Adubeiro,S., Roudot-Thoraval,F., Dubois-Rande,J.L., Hittinger,L., Pecker,F. N-acetylcysteine treatment normalizes serum tumor necrosis factor-alpha level and hinders the progression of cardiac injury in hypertensive rats. Circulation 2004; 110(-14-):2003-2009. >>> L-NAME; SC; Rat; 2ML4; 4,6 weeks; Functionality of mp verified by systolic blood pressure; pumps replaced after 4 weeks; enzyme inhibitor (no synthase); cardiovascular.

P7024 De Seranno,S., Estrella,C., Loyens,A., Cornea,A., Ojeda,S.R., Beauvillain,J.C., Prevot,V. Vascular endothelial cells promote acute plasticity in ependymoglial cells of the neuroendocrine brain. Journal of Neuroscience 2004; 24(-46-):10353-10363. >>> L-NAME; Sodium chloride; CSF/CNS (median eminence); Rat; 2002; 2 weeks; Controls received mp w/ vehicle; functionality of mp verified by determining correct cannula placement and exhaustion of infusion solution; enzyme inhibitor (NOS).

P6488 Wheeler,M.T., Allikian,M.J., Heydemann,A., Hadhazy,M., Zarnegar,S., McNally,E.M. Smooth muscle cell-extrinsic vascular spasm arises from cardiomyocyte degeneration in sarcoglycan-deficient cardiomyopathy. Journal of Clinical Investigation 2004; 113(-5-):668-675. >>> L-NAME; IP; Mice (transgenic); 6 days; Controls received mp w/ saline; enzyme inhibitor (no synthase); cardiovascular.

P6271 McDonald,W.S., Lo,TP Jr, Thurmond,M., Jones,C., Cohen,R., Miller,A., Beasley,D. Role of nitric oxide in skin flap delay. PLASTIC AND RECONSTRUCTIVE SURGERY 2004; 113(-3-):927-931. >>> L-NAME; IP; Mice; 1003D; ; Functionality of mp verified by residual volume; dose-response (p. 929); enzyme inhibitor (NOS).

R0191 Hofseth,L.J., Hussain,S.P., Wogan,G.N., Harris,C.C. Nitric oxide in cancer and chemoprevention. Free Radical Biology and Medicine 2003; 34(-8-):955-968. >>> L-NAME; Mice; ; Cancer (breast); pg. 958, Table 2, ref. 218.

P6257 Elger,W., Beier,S., Pollow,K., Garfield,R., Shi,S.Q., Hillisch,A. Conception and pharmacodynamic profile of drospirenone. Steroids 2003; 68(-10-13-):891-905. >>> L-NAME; SC; Rat (pregnant); 10 days; Teratology; pump model not listed.

P6083 Turban,S., Wang,X.Y., Knepper,M.A. Regulation of NHE3, NKCC2, and NCC abundance in kidney during aldosterone escape phenomenon: role of NO. American Journal of Physiology-Renal Physiology 2003; 285(-5-):F843-F851. >>> Angiotensin II; aldosterone; L-NAME; Acetic acid; DMSO; saline; water; SC; Rat; 2001; 2ML1; 7 days; Controls received mp w/ vehicle; peptides; angiotensin II dissolved in acetic acid; albo dissolved in 30% DMSO/saline; L-NAME dissolved in water.

P5994 Murase,T., Tian,Y., Fang,X.Y., Verbalis,J.G. Synergistic effects of nitric oxide and prostaglandins on renal escape from vasopressin-induced antidiuresis. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 2003; 284(-2-):R354-R362. >>> Vasopressin, 1-desamino-8-D arginine; L-NAME; diclofenac; ranitidine; Saline; DMSO; SC; Rat; 2001; 2002; 5 days; Vasopressin, 1-desamino-8-D arginine was infused in the 2002 pump; L-NAME was dissolved in saline and diclofenac was dissolved in 50% DMSO; both were infused from a 2001 pump.

P5917 Packer,M.A., Stasiv,Y., Benraiss,A., Chmielnicki,E., Grinberg,A., Westphal,H., Goldman,S.A., Enikolopov,G. Nitric oxide negatively regulates mammalian adult neurogenesis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2003; 100(-16-):9566-9571. >>> L-Name; D-Name; Calcium; Hank's buffered saline; CSF/CNS; Rat; 2002; ; Enzyme inhibitor (nitric oxide sythase).

P5906 Nadeau,S., Rivest,S. Glucocorticoids play a fundamental role in protecting the brain during innate immune response. Journal of Neuroscience 2003; 23(-13-):5536-5544. >>> Tumor necrosis factor-alpha; L-NAME; endotoxin, LPS; Saline; BSA; ascorbic acid; PIPES; DMSO; CSF/CNS (cortex, dorsal basal ganglia); Rat; 2004; 3,7,14,21 days; Controls received mp w/ vehicle; tissue perfusion (cerebral tissue&dorsal ganglia); enzyme inhibitor (nitric oxide); brain tissue distribution; guid cannula used; TNF-a was dissolved in saline + 0.1% BSA + 0.01% ascorbic acid; L-NAME was dissolved in PIPES&10% DMSO&infused into the dorsal basal ganglia.

P5899 Kurisu,S., Ozono,R., Oshima,T., Kambe,M., Ishida,T., Sugino,H., Matsuura,H., Chayama,K., Teranishi,Y., Iba,O., Amano,K., Matsubara,H. Cardiac angiotensin II type 2 receptor activates the kinin/NO system and inhibits fibrosis. Hypertension 2003; 41(-1-):99-107. >>> Angiotensin II; HOE 140; L-NAME; Saline; SC; Mice (transgenic); 2002; 14 days; Controls received mp w/ vehicle; enzyme inhibitor (no); cardiovascular; HOE140 is a bradykinin B2 receptor antagonist; L-NAME is a nitric oxide synthase inhibitor; table on p. 101 for weights, blood pressure, heart rate, etc..

P5730 Buckwalter,J.B., Curtis,V.C., Valic,Z., Ruble,S.B., Clifford,P.S. Endogenous vascular remodeling in ischemic skeletal muscle: a role for nitric oxide. Journal of Applied Physiology 2003; 94(-3-):935-940. >>> L-NAME; D-NAME; Phenylephrine; Saline; heparin; IA (femoral); Rabbit; 2ML2; 6 weeks; Controls received mp w/ phenylephrine or D-NAME; enzyme inhibitor (Nitric oxide synthase); cardiovascular; peptides; L-NAME&D-NAME (no synthase inhibitors) were dissolved in heparinized saline (100 U/ml).

P5611 Witlin,A.G., Gangula,P.R.R., Wimalawansa,S.J., Grafe,M., Grady,J.J., Yallampalli,C. Adrenomedullin requires an intact nitric oxide system to function as a nendogenous vasodilator in rat gestation. HYPERTENSION IN PREGNANCY 2003; 22(-1-):9-24. >>> Adrenomedullin, human; L-NAME; SC; Rat (pregnant); 1003D; 2001D; 2ML1; 2ML2; 1-5 days; Controls received mp/w vehicle; dose-response (table, p. 17); teratology; peptides; antihypertensive; agents infused individually or in combination..

P6655 Li,X., Simard,J.M. Increase in Cx45 gap junction channels in cerebral smooth muscle cells from SHR. Hypertension 2002; 40(-6-):940-946. >>> Angiotensin II; L-NAME; captopril; SC; Rat; 4 weeks; Enzyme inhibitor (nitric oxide synthase); cardiovascular; antihypertensive.

P5846 Nemade,R.V., Carrette,O., Larsen,W.J., Markoff,E. Involvement of nitric oxide and the ovarian blood follicle barrier in murine follicular cyst development. Fertility and Sterility 2002; 78(-6-):1301-1308. >>> L-NAME; D-NAME; Gonadotrophin, human chorionic; Water, sterile; SC; Mice; 1003D; 1007D; 3,4,7 days; Functionality of mp verified by plasma levels taken; enzyme inhibitor (nitric oxide synthase) "L-NAME"; multiple pumps per animal in some groups; human choriogonadotropin is (hCG).

1353 Berceli,S.A., Davies,M.G., Kenagy,R.D., Clowes,A.W. Flow-induced neointimal regression in baboon polytetrafluoroethylene g rafts is associated with decreased cell proliferation and increased ap optosis. JOURNAL OF VASCULAR SURGERY 2002; 36(-6-):1248-1255. >>> ; .

P5371 Tam,S.L., Sims,E., Kaufman,S. Effect of NOS inhibition on central response to atrial distension during pregnancy. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 2002; 283(-4-):R827-R831. >>> L-NAME; D-NAME; SC; Rat (pregnant); 2ML1; ; Enzyme inhibitor.

P5300 Horstman,D.J., Fischer,L.G., Kouretas,P.C., Hannan,R.L., Rich,G.F. Role of nitric oxide in heparin-induced attenuation of hypoxic pulmonary vascular remodeling. J Appl.Physiol 2002/5; 92(-5-):2012-2018. >>> L-NAME; Heparin; Saline; SC; Rat; 2ML4; 3 days or 3 weeks; Controls received mp w/ vehicle; cardiovascular; 24 hour recovery period.

P5156 Tam,S.L., Kaufman,S. NOS inhibition restores renal responses to atrial distension during pregnancy. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 2002; 282(--):R1364-R1367. >>> L-NAME; D-NAME; SC; rat (pregnant); 2ML1; 6 days; controls received mp w/ inactive agent; cardiovascular; enzyme inhibitor (NOS).

P4877 Ikegaki,I., Hattori,T., Yamaguchi,T., Sasaki,Y., Satoh,S., Asano,T., Shimokawa,H. Involvement of Rho-kinase in vascular remodeling caused by long-term inhibition of nitric oxide synthesis in rats. European Journal of Pharmacology 2001; 427(--):69-75. >>> L-NAME; IP; rat; 2ML4; 28 days; controls received no treatment; cardiovascular; L-NAME is a nitric oxide synthesis inhibitor.

P4784 Buhimschi,I.A., Shi,S.Q., Saade,G.R., Garfield,R.E. Marked variation in responses to long-term nitric oxide inhibition during pregnancy in outbred rats from two different colonies.. American Journal of Obstetrics and Gynecology 2001; 184(-4-):686-693. >>> L-NAME;; Saline;; SC;; rat (pregnant);; 2ML2; 2ML4;; 14 or 28 days;; Controls received mp w/ vehicle; teratology; enzyme inhibitor; L-NAME is a nitric oxide synthase inhibitor;.

P4673 Paterson,S, Zheng,Y, Smith,P.F., Darlington,C.L. The effects of L-NAME on vestibular compensation and NOS activity in the vestibular nucleus, cerebellum and cortex of the guinea pig.. Brain Research 2000; 879(--):148-155. >>> L-NAME; Saline; SC; Guinea-pig; 1003D; 50 hours; Controls received mp w/ vehicle; functionality of mp verified by nitric oxide synthase activity; dose-response (p. 153); enzyme inhibitor; L-NAME is a nitric oxide synthase inhibitor;.

R0140 Li,J, Billiar,T.R. Nitric oxide IV. determination of nitric oxide protection and toxicity in liver. Am.J.Physiol. 1999; 276(--):G1069-G1073. >>> L-NMMA; L-NAME; Aminoguanidine; IV (hepatic portal);; rat;; ; nitric oxide synthase inhibitors;.

P5241 Murakami,H., Miao,R.Q., Chao,L., Chao,J. Adenovirus-mediated kallikrein gene transfer inhibits neointima formation via increased production of nitric oxide in rat artery. Immunopharmacology 1999/10/15; 44(-1-2-):137-143. >>> L-NAME; IP; Rat; 2ML2; 2 weeks; Cardiovascular.

P5107 Murakami,H, Miao,R.Q, Chao,L, Chao,J. Adenovirus-mediated kallikrein gene transfer inhibits neointima formation via increased production of nitric oxide in rat artery. Immunopharmacology 1999; 44(--):137-143. >>> L-NAME; IP; rat; 2ML2; 14 days; cardiovascular; L-Name is an enzyme inhibitor (NO synthase).

P4527 Bosmans,J.M, Vrints,C.J, Kockx,M.M, Bult,H, Cromheeke,K.M.C, Herman,A.G. Continuous perivascular L-Arginine delivery increases total vessel area and reduces neointimal thickening after experimental balloon dilatation.. Arterioscler.Thromb.Vasc.Biol. 1999; 19(--):767-776. >>> L-NAME; Arginine, L;; Water, deionized; NaCl, sterile;; IP;; rabbit;; 2ML2;; 2 weeks;; controls received mp w/vehicle; functionality of mp verified by residual volume and plasma levels; cardiovascular;.

P4510 Nowicki,B, Singhal,J, Fang,L, Nowicki,S, Yallampalli,C. Inverse relationship between severity of experimental pyelonephritis and nitric oxide production in C3H/HeJ mice.. Infection and Immunity 1999/5; 67(-5-):2421-2427. >>> L-NAME;; Saline;; SC;; mice;; ; controls received mp w/vehicle;.

P4475 Zlatnik,M.G., Buhimschi,I, Chwalisz,K., Liao,Q.-P., Saade,G.R., Garfield,R.E. The effect of indomethacin and prostacyclin agonists on blood pressure in a rat model of preeclampsia.. Am.J.Obstet.Gynecol. 1999/5; 180(-5-):1191-1195. >>> Iloprost; Cicaprost; L-NAME; Indomethacin; Saline;; SC;; rat (pregnant);; 2ML2;; 2 weeks;; controls received mp w/vehicle; comparison of SC injections vs. mp; cardiovascular; L-NAME is a synthase inhibitor;.

P4623 Wimalawansa,S.J, Yallampalli,C. Pre-eclamptic toxemia: potential new therapy based on animal studies.. Ceylon Medical Journal 1998; 43(--):138-144. >>> L-NAME; Calcitonin gene-related peptide; Saline, sterile;; SC;; rat(pregnant);; 2ML1;; 1 week;; controls received mp w/ vehicle; peptides; CGRP and L-NAME or vehicle delivered from separate pumps concomitantly..

P4585 Wang,H.H, Lautt,W.W. Evidence of nitric oxide, a flow-dependent factor, being a trigger of liver regeneration in rats.. Can.J.Physiol.Pharmacol. 1998; 76(--):1072-1079. >>> L-NAME;; Saline;; SC;; rat;; 2ML1;; ; controls received mp w/vehicle; functionality of mp verified by plasma levels;.

P3787 Bosmans,J.M, Vrints,C.J, Kockx,M.M, Bult,H, Cromheeke,K.M.C, Herman,A.G. Continuous perivascular L-arginine delivery increases total vessel area and reduces neointimal thickening after experimental balloon dilatation. Arterioscler Thromb Vasc Biol 1998; 19(-3-):767-776. >>> Arginine,L-; L-NAME; Water, deionized; Perivascular; Rabbit; 2ML2; 2 weeks; Controls received mp w/ saline; functionality of mp verified by residual volume; cardiovascular; Restenosis; L-arginine plasma levels checked.

P6318 Steudel,W., Ichinose,F., Huang,P.L, Hurford,W.E., Jones,R.C., Bevan,J.A., Fishman,M.C, Zapol,W.M. Pulmonary Vasoconstriction and Hypertension in Mice With Targeted Disruption of the Endothelial Nitric Oxide Synthase (NOS 3) Gene. Circulation Research 1997; 81(-1-):34-41. >>> L-NAME; Saline, normal; IP; Mice; 1007D; 5 days; Controls received no treatment; comparison of acute IV injections vs. mp; enzyme inhibitor (nitric oxide synthase); cardiovascular.

P4241 Ou,J., Carlos,T.M., Watkins,S.C., Saavedra,J.E., Keefer,L.K., Kim,Y.-M., Harbrecht,B.G., Billiar,T.R. Differential effects of nonselective nitric oxide synthase (NOS) and selective inducible NOS inhibition on hepatic necrosis, apoptosis, ICAM-1 expression, and neutrophil accumulation during endotoxemia. Nitric Oxide: Biology&Chemistry 1997; 1(-5-):404-416. >>> Aminoguanidine; Lysine, L-N6-(1-imino-ethyl)-; V-PYRRO/NO; L-NAME; L-NMA; Saline; IV (jugular); IV (gastric); rat; 2001D; 16 hours; controls received mp w/vehicle; good methods (p. 406); nitric oxide synthase inhibitors; PE10 catheter tubing inserted in gastric vein; some animals implanted with one pump for gastric vein and one for jugular vein; NMA is NG-monomethyl-L-arginine.

P3894 Rose,A.S., Prazma,J., Randell,S.H., Baggett,H.C., Lane,A.P., Pillsbury,H.C. Nitric oxide mediates mucin secretion in endotoxin-induced otitis media with effusion. Otolaryngol Head Neck Surg 1997; 116(--):308-316. >>> L-NAME; Kreb's solution; ear (tympanic bulla); rat; 2001; 7 days; controls received mp w/vehicle; tissue perfusion (tympanic bulla); good diagram of pump implantation (pg. 310).

P3861 Chatterjee,S., Collins,T.J., Yallampalli,C. Inhibition of nitric oxide facilitates LH release from rat pituitaries. Life Sci. 1997; 61(-1-):45-50. >>> Nitroglycerin; L-NAME; SC; rat; 2ML1; 36 hours; controls received mp w/saline.

P3836 Nakamura,T. Contribution of L-arginine-derived nitric oxide to the structural integrity of coronary artery and cardiac interstitium, and to the regulation of sympathetic nerve activity: assessment using a rat model produced by chronic nitric oxide inhibition. Hokkaido J.Med.Sci. 1997; 72(-5-):503-516. >>> L-NAME; IP; rat; 2ML4; 4,8 weeks; controls received mp w/saline; dose-response; long-term study, pumps replaced after 4 weeks; cardiovascular.

P3547 Gangula,P.R.R., Wimalawansa,S.J., Yallampalli,C. Progesterone up-regulates vasodilator effects of calcitonin gene-related peptide in NG-nitro-L-arginine methyl ester-induced hypertension. Am.J.Obstet.Gynecol. 1997; 176(--):894-900. >>> L-NAME; Calcitonin gene-related peptide; Saline, sterile; SC; rat (pregnant); 2ML2; no duration posted; controls received mp w/ saline; peptides; agents given singly and concomitantly in the same pump; cardiovascular.

P3408 Sander,M., Hansen,J., Victor,R.G. The sympathetic nervous system is involved in the maintenance but not initiation of the hypertension induced by No-nitro-L-arginine methyl ester. Hypertension 1997; 30(-Pt 1-):64-70. >>> L-NAME; IP; IV (jugular); rat; 2ML1; 6 days; comparison of bolus injections vs. mp; cardiovascular.

P4440 Danielson,L.A, Conrad,K.P. Prostaglandins maintain renal vasodilation and hyperfiltration during chronic nitric oxide synthase blockade on conscious pregnant rats.. Circ.Res. 1996; 79(--):1161-1166. >>> L-NAME;; Saline;; SC;; rat (pregnant);; 48 hours;; controls received mp w/vehicle; cardiovascular.

P3695 Liao,Q.-P., Buhimschi,I.A., Saade,G., Chwalisz,K., Garfield,R.E. Regulation of vascular adaptation during pregnancy and post-partum: effects of nitric oxide inhibition and steroid hormones. Human Reproduction 1996; 11(-12-):2777-2784. >>> L-NAME; Saline, sterile; SC; rat (pregnant); 2ML2; 14 days; controls received mp w/ vehicle; agent is NOS inhibitor.

P3630 Qiu,B.S., Pfeiffer,C.J., Cho,C.H. Effects of chronic nitric oxide sythase inhibition in cold-restraint and ethanol-induced gastric mucosal damage in rats. Digestion 1996; 57(--):60-66. >>> L-NAME; NaCl; SC; rat; 2002; 10 days; functionality of mp verified by hypertension after 5 days; dose response (see pg. 62); bupivacaine HCl given to minimize post-operative pain.

P3333 Thomas,D.A., Ren,K., Besse,D., Ruda,M.A., Dubner,R. Application of nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester, on injured nerve attentuates neuropathy-induced thermal hyperalgesia in rats. Neurosci.Lett. 1996; 210(--):124-126. >>> L-NAME; D-NAME; SC; CSF/CNS (sciatic nerve); rat; 2001; 2 weeks; controls received mp w/saline; tissue perfusion (nerve cuff); comparison of systemic vs. targeted infusion; pumps replaced on day 8.

P3690 Pfeiffer,C.J., Qiu,B.S. Effects of chronic nitric oxide synthase inhibition on TNB-induced colitis in rats. J.Pharm.Pharmacol. 1995; 47(--):827-832. >>> L-NAME; SC; rat; 2002; 8 days; controls received mp w/ saline; agent nitric oxide synthase inhibitor.

P3169 Shudo,H. L-arginine-nitric oxide pathway: nitric oxide. 1994; 69(-4-):967-977. >>> L-NAME; IP; rat; 4 weeks; controls received mp with saline; abstract and graphs in English; paper in Japanese.

P2589 Cayatte,A.J., Palacino,J.J., Horten,K., Cohen,R.A. Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler.Thromb. 1994; 14(-5-):753-759. >>> L-NAME; Water, deionized; SC; rabbit; 2ML4; 4 weeks; enzyme inhibitor; nitric oxide synthase inhibitor;.

P2585 Garcia-Pagan,J.C., Fernandez,M., Bernadich,C., Pizcueta,P., Pique,J.M., Bosch,J., Rodes,J. Effects of continued NO inhibition on portal hypertensive syndrome after portal vein stenosis in rat. Am.J.Physiol. 1994; 267(-30-):G984-G990. >>> L-NAME; Saline; SC; rat; 2ML2; 4 or 8 days; controls received mp w/ vehicle or no surgery; stability verified at 37 degrees by earlier 14-day bolus injection study; enzyme inhibitor; nitric oxide synthase inhibitor;.

P2588 Khan,F., Palacino,J.J., Coffman,J.D., Cohen,R.A. Chronic inhibition of nitric oxide production augments skin vasoconstriction in the rabbit ear. J.Cardiovasc.Pharmacol. 1993; 22(-2-):280-286. >>> L-NAME; Water, deionized; SC; rabbit; 2ML4; 2 or 4 weeks; controls received mp w/ saline; enzyme inhibitor; nitric oxide synthase inhibitor;.

P2587 Adams,M.L., Kalicki,J.M., Meyer,E.R., Cicero,T.J. Inhibition of the morphine withdrawal syndrome by a nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester. Life Sci. 1993; 52(--):L-249. >>> L-NAME HCl; Saline; Water; SC; rat; 2001; 7 days; controls received mp w/ saline; dependence; enzyme inhibitor; nitric oxide synthase inhibitor.

P2586 Yallampalli,C., Garfield,R.E. Inhibition of nitric oxide synthesis in rats during pregnancy produces signs similar to those of preeclampsia. Am.J.Obstet.Gynecol. 1993; 169(--):1316-1320. >>> L-NAME; Nitroglycerin; Saline; SC; rat (pregnant); 2ML2; no duration posted; controls received mp w/ saline only; L-nitro-arginine methyl ester is L-NAME and is a nitric oxide synthase inhibitor; teratology; enzyme inhibitor.

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3. L-NMA

P5591 Presle,N., Cipolletta,C., Jouzeau,J.Y., Abid,A., Netter,P., Terlain,B. Cartilage protection by nitric oxide synthase inhibitors after intraarticular injection of interleukin-1beta in rats. Arthritis Rheum. 1999/10; 42(-10-):2094-2102. >>> L-NMA; Saline; IP; Rat; 1003D; 72 hours; Controls received mp w/ vehicle; enzyme inhibitor; nitric oxide synthase inhibitors; L-NMA also called N-monomethyl-L-arginine.

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4. L-NMMA

P7793 Seto,S., Nagao,S., Ozeki,S., Tetsuo,H., Akahoshi,M., Yano,K. Contribution of central nitric oxide to the regulation of blood pressure and sodium balance in DOCA-salt hypertension. Journal of Cardiovascular Pharmacology 2006; 47(-5-):680-685. >>> L-NMMA; IP; CSF/CNS; Rat; 2ML4; 4 weeks; Controls received mp w/ saline; replacement therapy (nephrectomy); dose-response (fig. 1); enzyme inhibitor (no synthase); cardiovascular; animal info (male, Wistar, 7 wk. old, 240g.); cannula location confirmed by methylene blue staining.

P7271 Kashiwagi,S., Izumi,Y., Gohongi,T., Demou,Z.N., Xu,L., Huang,P.L., Buerk,D.G., Munn,L.L., Jain,R.K., Fukumura,D. NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels. Journal of Clinical Investigation 2005; 115(-7-):1816-1827. >>> L-NMMA; D-NMMA; SC; Mice; mice (SCID); 1002; 8, 21 days; Controls received mp w/ D-NMMA; pumps replaced at day 14; enzyme inhibitor (NO synthase); cancer (melanoma); cardiovascular; eNOS -/- mice; iNOS -/- mice.

P6845 Hagendoorn,J., Padera,T.P., Kashiwagi,S., Isaka,N., Noda,F., Lin,M.I., Huang,P.L., Sessa,W.C., Fukumura,D., Jain,R.K. Endothelial nitric oxide synthase regulates microlymphatic flow via collecting lymphatics. Circulation Research 2004; 95(-2-):204-209. >>> L-NMMA; D-NMMA; SC; Mice; 3 days; Controls received mp w/ D-NMMA; enzyme inhibitor (NO synthase); cardiovascular.

P6754 Momohara,Y., Sakamoto,S., Obayashi,S., Aso,T., Goto,M., Azuma,H. Roles of endogenous nitric oxide synthase inhibitors and endothelin-1 for regulating myometrial contractions during gestation in the rat. MOLECULAR HUMAN REPRODUCTION 2004; 10(-7-):505-512. >>> L-NMMA; IP; Rat; 2 weeks; Controls received mp w/ saline; enzyme inhibitor (no synthase).

P4418 Schaffer,M.R., Tantry,U., Thornton,F.J, Barbul,A. Inhibition of nitric oxide synthesis in wounds: pharmacology and effect on accumulation of collagen in wounds in mice.. Eur.J.Surg. 1999; 165(--):262-267. >>> L-NMMA; Aminoguanidine hemisulphate; MITU;; PBS;; IP;; mice;; 10 days;; control received mp w/vehicle; comparison of IP injections vs. mp; wound healing study; MITU is S-methyl isothiouronium, a competitive NO synthase inhibitor..

P4228 Wada,Y., Matsuoka,H., Okuda,S., Imaizumi,T. Chronic inhibition of nitric oxide in central nervous system does not cause hypertension. Hypertension Res. 1998; 21(--):97-101. >>> L-NMMA; D-NMMA; CSF/CNS (cisterna magna); rat; 2001; 7 days; controls received mp w/D-NMMA; no stress (p. 98); nitric oxide synthase inhibitor; L-NMMA is N6-monomethyl-L-arginine; silastic PE10 tubing connected to PE50 tubing; pump implanted 7 days after cannula implantation; catheter patency verified; cardiovascular.

P3522 Suzuki,Y., Ikari,H., Hayashi,T., Iguchi,A. Central administration of a nitric oxide synthase inhibitor impairs spatial memory in spontaneous hypertensive rats. Neuroscience Letters 1996; 207(--):105-108. >>> L-NMMA; Saline; Trypan blue; CSF/CNS (dorsal third ventricle); rat; 2001; no duration posted; agent is N-monomethyl-L-arginine; enzyme inhibitor: nitric oxide synthase.

P3473 Cohen,T.I., Weinberg,R.J., Blight,A.R. Intrathecal infusion of the Nitric Oxide Synthase Inhibitor N-methyl L-arginine after experimental spinal cord injury in guinea pigs. J.Neurotrauma 1996; 13(-7-):361-369. >>> L-NMMA; D-NMMA; CSF/CNS (spinal cord, intrathecal); guinea-pig; 2001; no duration posted; no comment posted.

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5. L-NNA

P4395 Cramer,K.S., Angelucci,A., Hahm,J.-O., Bogdanov,M.B., Sur,M. A role for nitric oxide in the development of the ferret retinogeniculate projection. Journal of Neuroscience 1996/10/15; 16(-24-):7995-8004. >>> L-NNA;; Saline;; CSF/CNS (lateral geniculate nucleus);; ferret;; 12 days;; 2002;; controls received mp with saline; animals received antibiotics prophylactically;.

P2574 Kimes,A.S., Vaupel,D.B., London,E.D. Attenuation of some signs of opioid withdrawal by inhibitors of nitric oxide synthase. Psychopharmacology 1993; 112(--):521-524. >>> L-NNA; Saline; SC; rat; 2ML1; 8 days; controls received mp w/ saline; comparison of ip injections vs mp; Injected L-NNA "was more effective than continuous infusion"; L-NNA is L-N-nitroarginine and is a NOS inhibitor.

P2483 Lee,F-Y., Colombato,L.A., Albillos,A., Groszmann,J.R. N-Nitro-L-arginine administration corrects peripheral vasodilation and systemic capillary hypotension and ameliorates plasma volume expansion and sodium retention in portal hypertensive rats. Hepatology 1993; 17(-1-):84-90. >>> L-NNA; Heparin; Saline; IV (jugular); rat; 2ML1; 6 days; heparin added for anticoagulation; NNA stable for at least 6 days (p. 85).

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6. MITU

P3442 Schaffer,M.R., Tantry,U., Gross,S.S., Wasserkrug,H.L., Barbul,A. Nitric oxide regulates wound healing. J.Surg.Res. 1996; 63(--):237-240. >>> MITU; IP; mice; 10 days; controls received mp w/ PBS; immunology; MITU is S-methyl isothiouronium, a competitive NO synthase inhibitor; wound healing.

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7. MLA

P8382 Pocivavsek,A., Icenogle,L., Levin,E.D. Ventral hippocampal a7 and a4b2 nicotinic receptor blockade and clozapine effects on memory in female rats. Psychopharmacology 2006; 188(-4-):597-604. >>> Nicotine ditartrate; MLA; Erythroidine, dihydro-beta; Saline, sterile; CSF, artifical; SC; CSF/CNS (ventral hippocampus); Rat; 2004; 2ML4; 4 weeks; Controls received mp w/ vehicle; multiple pumps per animal (2); animal info (female, Sprague-Dawley, 200-300g.); neurodegenertive (Alzheimer's disease); Methyllycarconitine; cannula placement confirmed w/ Chicago sky-blu dye; Schizophrenia.

P7098 Kawakami,K., Kawakami,M., Puri,R.K. Nitric oxide accelerates interleukin-13 cytotoxin-mediated regression in head and neck cancer animal model. Clinical Cancer Research 2004; 10(-15-):5264-5270. >>> MLA; IP; Mice (nude); 1007D; 7 days; Cancer (head, neck); MLA is NW-monomethyl-L-arginine.

P4198 Yim,C.-Y., Lee,C.-W., Choi,S.-M., Park,S.-S., Lee,S.-J., Kim,J.-H., Song,J.-S., Yoo,W.-H., Kwak,J.-Y., Sohn,M.-H. Effects of nitric oxide (NO) synthesis inhibition on antitumor responses during interleukin-2 (IL-2) treatment of mice. Korean J.Internal Med. 1996; 11(-2-):93-100. >>> MLA; SC; mice; 2001; no duration posted; controls received sham implantation; MLA is n-monomethyl-L-arginine, an NOS inhibitor; cancer; immunology.

P3553 Samlowski,W.E., Yim,C.-Y., McGregor,J.R., Kwon,O.-D., Gonzales,S., Hibbs Jr,J.B. Effectiveness and toxicity of protracted nitric oxide synthesis inhibition during IL-2 treatment of mice. J.Immunother. 1995; 18(-3-):166-178. >>> MLA; SC; mice; 2001; 1007D; no duration posted; controls received sham implantation or no treatments; immunology; toxicology.

P2804 Yim,C.-Y., McGregor,J.R., Kwon,O.-D., Bastian,N.R., Rees,M., Mori,M., Hibbs Jr,J.B., Samlowski,W.E. Nitric oxide synthesis contributes to IL-2-induced antitumor responses against intraperitoneal Meth A tumor. J.Immunol. 1995; 155(--):4382-4390. >>> MLA; SC; mice; 2001; 8 days; controls received sham surgery; pumps replaced after 8 days; cancer; MLA is N-monomethyl-L-arginine, an NOS inhibitor.

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8. Methylisothiourea, S-

P4781 Efron,D.T., Most,D., Shi,H.P., Tantry,U.S., Barbul,A. A novel method of studying wound healing.. Journal of Surgical Research 2001; 98(--):16-20. >>> Methylisothiourea,S-; Adenovirus vector; Gene, mouse iNOS cDNA sequence;; Saline; Dye, methlene blue; Dye, India black ink; PBS; SC (wound healing site);; rat;; 2001; 2ML1;; 7 days;; Controls received mp w/ saline; functionality of mp verified by dye infusion; gene therapy; enzyme inhibitor; methylisothiourea,S- is an inducible nitric oxide synthase inhibitor (iNOS inhibitor); wound healing; SC-implanted pumps infused 2 hydroxyproline sponges via catheter; initial studies used 2ML1 pumps to infuse dyes in order to assess the feasibility of direct infusion with pumps; iNOS inhibitor infusion was with 2001 pumps; pumps were designed to infuse directly into SC implanted polyvinyl sponges at the wound site; Adenovirus vector was dissolved in PBS; iNOS inhibitor was delivered in saline; diagram of pump-catheter assembly and location (p. 18); "Dye infusion demonstrated both grossly and microscopically excellent delivery of the infusate to wound sponges" (p. 18);.

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9. Nitroindazole

P8379 Thippeswamy,T., Haddley,K., Corness,J.D., Howard,M.R., McKay,J.S., Beaucourt,S.M., Pope,M.D., Murphy,D., Morris,R., Hoekfelt,T., Quinn,J.P. NO-cGMP mediated galanin expression in NGF-deprived or axotomized sensory neurons. Journal of Neurochemistry 2007; 100(-3-):790-801. >>> Nitroindazole, 7-; DMSO; IP; Rat; 2ML1; 7 days; Controls received mp w/ vehicle; replacement therapy (axotomy); animal info (male, Wistar, Albino, 250-280g.); 20% DMSO.

P7078 Kim,E.Y., Shin,K.M., Jang,S., Oh,S.W. Changes of [3H]muscimol, [3H]flunitrazepam and [3H]MK-801 binding in rat brain by prolonged ventricular infusion of 7-nitroindazole. Neurochemical Research 2004; 29(-12-):2221-2229. >>> Nitroindazole, 7-; CSF/CNS; Rat; 2ML1; 7 days; Controls received mp w/ saline; enzyme inhibitor (nitric oxide synthase); cyanoacrylate adhesive.

P3492 Bazzett,T., Geiger,A., Coppola,B., Albin,R. The neuronal NOS inhibitor L-MIN, but not 7-NINA, reduces neurotoxic effects of chronic intrastriatal administration of quinolinic acid. Brain Research 1997; 775(--):229-232. >>> Quinolinic acid; Nitroindazole, 7-, sodium salt; thiocitrulline dihydrochloride, methyl-; PBS; CSF/CNS (striatum); rat; 2002; no duration posted; dose-response; microdialysis; quinolinic acid administered alone or w/1 other agent in same pump; enzyme inhibitor; nitric oxide synthase inhibitor;.

P3444 O'Neill,M.J., Hicks,C., Ward,M. Neuroprotective effects of 7-nitroindazole in the gerbil model of global cerebral ischaemia. Eur.J.Pharmacol. 1996; 310(--):115-122. >>> Nitroindazole, 7-, sodium salt; IP; gerbil; 1003D; 72 hours; comparison of ip injections vs. mp; 2 pumps implanted in each animal; 7-nitroindazole is a neuronal nitric oxide sythase inhibitor; neuroprotection seen when 7-nitroindazole was infused via mp, but not when injected 12X after occlusion.

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10. Thiocitrulline Dihydrochloride, Methyl-

P3492 Bazzett,T., Geiger,A., Coppola,B., Albin,R. The neuronal NOS inhibitor L-MIN, but not 7-NINA, reduces neurotoxic effects of chronic intrastriatal administration of quinolinic acid. Brain Research 1997; 775(--):229-232. >>> Quinolinic acid; Nitroindazole, 7-, sodium salt; Thiocitrulline dihydrochloride, methyl-; PBS; CSF/CNS (striatum); rat; 2002; no duration posted; dose-response; microdialysis; quinolinic acid administered alone or w/1 other agent in same pump; enzyme inhibitor; nitric oxide synthase inhibitor;.

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References on the Administration of Nitric Oxide Synthase Inhibitors Using ALZET® Osmotic Pumps

1. 1400W

2. L-NAME

3. L-NMA

4. L-NMMA

5. L-NNA

6. MITU

7. MLA

8. Methylisothiourea, S-

9. Nitroindazole

10. Thiocitrulline Dihydrochloride, Methyl-

Sterile Catheter Tubing for Infusion Studies

References on the Administration of Nitric Oxide Synthase Inhibitors Using
ALZET^® Osmotic Pumps