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

1. 1400W

14811 Ager, E.I., Kozin, S.V., Kirkpatrick, N.D., Seano, G., Kodack, D.P., Askoxylakis, V., Huang, Y.H., Goel, S., Snuderl, M., Muzikansky, A., Finkelstein, D.M., Dransfield, D.T., Devy, L., Boucher, Y., Fukumura, D., Jain, R.K., Jain, R.K. Blockade of MMP14 Activity in Murine Breast Carcinomas: Implications for Macrophages, Vessels, and Radiotherapy. JOURNAL OF THE NATIONAL CANCER INSTITUTE 2015; 107(--):U137-U148. >>> 1400W dihydrochloride; SC; Mice (nude); 1002; Animal info (female, nu/nu, 6-8 weeks old); cancer (breast); enzyme inhibitor (nitric oxide synthase); immunology;.

13398 Klug, F., Prakash, H., Huber, P.E., Seibel, T., Bender, N., Halama, N., Pfirschke, C., Voss, R.H., Timke, C., Urnansky, L., Klapproth, K., Schaekel, K., Garbi, N., Jaeger, D., Weitz, J., Schmitz-Winnenthal, H., Haemmerling, G.J., Beckhovel, P. Low-Dose Irradiation Programs Macrophage Differentiation to an iNOS(+)/M1 Phenotype that Orchestrates Effective T Cell Immunotherapy. CANCER CELL 2013; 24(-5-):589-602. >>> 1400W; PBS; SC; Mice; Controls received mp w/ vehicle; animal info (RT5); cancer (cancer immunotherapy); immunology; iNOS inhibitor.

11524 Nishida, M., Ogushi, M., Suda, R., Toyotaka, M., Saiki, S., Kitajima, N., Nakaya, M., Kim, K.M., Ide, T., Sato, Y., Inoue, K., Kurose, H. Heterologous down-regulation of angiotensin type 1 receptors by purinergic P2Y(2) receptor stimulation through S-nitrosylation of NF-kappaB. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2011; 108(-16-):6662-6667. >>> 1400W; suramin; Saline; Mice; Controls received mp w/ vehicle; animal info (C57BL/6J, 6 wks old, male); enzyme inhibitor (NO synthase, iNOS).

9118 Hu, A.H., Jiao, X.Y., Gao, E.H., Li, Y.H., Sharifi-Azad, S., Grunwald, Z., Ma, X.L., Sun, J.Z. Tonic beta-adrenergic drive provokes proinflammatory and proapoptotic changes in aging mouse heart. REJUVENATION RESEARCH 2008; 11(-1-):215-226. >>> 1400W; Isoproterenol bitartrate; SC; Mice; 2002; Controls received mp w/ vehicle; enzyme inhibitor (iNOS); animal info (C57BL/6, 3, 20 months old); ischemia (myocardial).

9101 Chirino, Y.I., Trujillo, J., Sanchez-Gonzalez, D.J., Martinez-Martinez, C.M., Cruz, C., Bobadilla, N.A., Pedraza-Chaverri, J. Selective iNOS inhibition reduces renal damage induced by cisplatin. TOXICOLOGY LETTERS 2008; 176(-1-):48-57. >>> 1400W; cisplatin; Saline; SC; Rat; 2001; Controls received mp w/ vehicle; enzyme inhibitor (iNOS); animal info (male, Wistar, 230-275g.).

8754 Zhang, P., Xu, X., Hu, X.L., van Deel, E.D., Zhu, G.S., Chen, Y.J. Inducible nitric oxide synthase deficiency protects the heart from systolic overload-induced ventricular hypertrophy and congestive heart failure. Circulation Research 2007; 100(-7-):1089-1098. >>> 1400W; Saline; SC; Mice; 2002; Controls received mp w/ vehicle; cardiovascular; animal info (2-3 months old, CS7BL16).

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2. L-NAME

16141 Netti, V. A., Iovane, A. N., Vatrella, M. C., Zotta, E., Fellet, A. L., Balaszczuk, A. M. Effects of nitric oxide system and osmotic stress on Aquaporin-1 in the postnatal heart. Biomed Pharmacother 2016; 81(--):225-34. >>> L-NAME; Saline; SC; Rat; 1003D; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 25-50 days old); cardiovascular; L-NAME solution prepared in laminar flow cabinet and used filter; Dose (4 mg/kg/day);.

15930 Pojoga, L. H., Yao, T. M., Opsasnick, L. A., Siddiqui, W. T., Reslan, O. M., Adler, G. K., Williams, G. H., Khalil, R. A. Cooperative Role of Mineralocorticoid Receptor and Caveolin-1 in Regulating the Vascular Response to Low Nitric Oxide-High Angiotensin II-Induced Cardiovascular Injury. J Pharmacol Exp Ther 2015; 355(-1-):32-47. >>> Angiotensin II; L-NAME; SC; animal info (male, cav-1 KO, 12 weeks old); AngII infused to induce cardiovascular injury; Dose (L-NAME 0.1 - 0.2 mg/mL; AngII 0.7-2.8 mg/kg/day);.

15097 Tain, Y.L., Huang, L.T., Chan, J.Y.H., Lee, C.T., Tain, Y.L. Transcriptome Analysis in Rat Kidneys: Importance of Genes Involved in Programmed Hypertension. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 2015; 16(--):4744-4758. >>> L-NAME; SC; Rat (pregnant); Controls received mp w/ saline, iso-osmotic; animal info (female, Sprague Dawley); teratology; cardiovascular; bp measured using tail cuff;.

14424 Tain, Y.L., Huang, L.T., Lee, C.T., Chan, J.Y.H., Hsu, C.N., Tain, Y.L. Maternal Citrulline Supplementation Prevents Prenatal N(G)-Nitro-L-Arginine-Methyl Ester (L-NAME)-Induced Programmed Hypertension in Rats. Biology of Reproduction 2015; 92(--):U27-U33. >>> L-NAME; SC; Rat (pregnant); Animal info (female, Sprague Dawley, 10 weeks old); teratology; cardiovascular;.

14423 Tain, Y.L., Lee, C.T., Huang, L.T., Tain, Y.L. Long-Term Effects of Maternal Citrulline Supplementation on Renal Transcriptome Prevention of Nitric Oxide Depletion-Related Programmed Hypertension: The Impact of Gene-Nutrient Interactions. International Journal of Molecular Sciences 2014; 15(--):23255-23268. >>> L-NAME; SC; Rat (pregnant); Controls received mp w/ saline; animal info (female, Sprague Dawley, 10 weeks old); teratology; cardiovascular;.

13570 Zana-Taieb, E., Butruille, L., Franco-Montoya, M.L., Lopez, E., Vernier, F., Grandvuillemin, I., Evain-Brion, D., Deruelle, P., Baud, O., Delacourt, C., Jarreau, P.H. Effect of Two Models of Intrauterine Growth Restriction on Alveolarization in Rat Lungs: Morphometric and Gene Expression Analysis. PLoS One 2013; 8(-11-):U35-U45. >>> L-NAME; Saline; SC; Rat (pregnant); Controls received high protein diet; animal info (Female, Sprague Dawley); teratology.

13402 Kurabayashi, A., Kakinuma, Y., Morita, T., Inoue, K., Sato, T., Furihata, M. Conditional VHL Gene Deletion Causes Hypoglycemic Death Associated with Disproportionately Increased Glucose Uptake by Hepatocytes through an Upregulated IGF-I Receptor. PLoS One 2013; 8(-7-):U1405-U1415. >>> L-NAME; Insulin-like growth factor 1 receptor; Saline; acetic acid; SC; Mice; Controls received mp w/ vehicle; animal info (VHL-KO); 25% acetic acid used; immunology.

13324 Abe, H., Ishikawa, W., Kushima, T., Nishimura, T., Mori, C., Onuki, A., Suzuki, T., Ishii, Y., Kansaku, N., Miyazaki, Y., Tanaka, K., Morita, H., Takizawa, T. Nitric Oxide Induces Vascular Endothelial Growth Factor Expression in the Rat Placenta in Vivo and in Vitro. BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 2013; 77(-5-):971-976. >>> L-NAME; SC; Rat (pregnant); 2001D; Animal info (Crj Wistar); enzyme inhibitor (NOS, nitric oxide).

12904 Butruille, L., Mayeur, S., Moitrot, E., Storme, L., Knauf, C., Lesage, J., Deruelle, P. Maternal hypertension induced by NO blockade does not program adult metabolic diseases in growth-restricted rat fetuses. METABOLISM-CLINICAL AND EXPERIMENTAL 2013; 62(-3-):442-445. >>> L-NAME; SC; Rat (pregnant); 2ML1; Control animals received mp w/ saline; animal info (Wistar Han, female, E17).

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3. L-NMA

5739 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; 42(-10-):2094-2102. >>> L-NMA; Saline; IP; Rat; 1003D; Controls received mp w/ vehicle; enzyme inhibitor; nitric oxide synthase inhibitors; L-NMA also called N-monomethyl-L-arginine.

4343 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; 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.

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4. L-NMMA

8009 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; 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.

7481 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; Controls received mp w/ D-NMMA; pumps replaced at day 14; enzyme inhibitor (NO synthase); cancer (melanoma); cardiovascular; eNOS -/- mice; iNOS -/- mice.

7054 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; Controls received mp w/ D-NMMA; enzyme inhibitor (NO synthase); cardiovascular.

6962 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; Controls received mp w/ saline; enzyme inhibitor (no synthase).

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5. L-NNA

4497 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; 16(-24-):7995-8004. >>> L-NNA; Saline; CSF/CNS (lateral geniculate nucleus); Ferret; 2002; Controls received mp with saline; animals received antibiotics prophylactically.

2662 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; 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.

2570 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; heparin added for anticoagulation; NNA stable for at least 6 days (p. 85).

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6. MITU

4523 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;; control received mp w/vehicle; comparison of IP injections vs. mp; wound healing study; MITU is S-methyl isothiouronium, a competitive NO synthase inhibitor..

3550 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; controls received mp w/ PBS; immunology; MITU is S-methyl isothiouronium, a competitive NO synthase inhibitor; wound healing.

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7. MLA

8608 Pocivavsek, A., Icenogle, L., Levin, E.D. Ventral hippocampal alpha7 and alpha4beta2 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; Controls received mp w/ vehicle; multiple pumps per animal (2); animal info (female, Sprague-Dawley, 200-300g.); neurodegenerative (Alzheimer's disease); methyllycaconitine; cannula placement confirmed w/ Chicago sky-blue dye; schizophrenia.

7307 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; Cancer (head, neck); MLA is NW-monomethyl-L-arginine.

4301 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; controls received sham implantation; MLA is n-monomethyl-L-arginine, an NOS inhibitor; cancer; immunology.

3661 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; controls received sham implantation or no treatments; immunology; toxicology.

2905 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; 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-

10060 Wu, K.L.H., Hsu, C., Chan, J.Y.H. Nitric Oxide and Superoxide Anion Differentially Activate Poly(ADP-ribose) Polymerase-1 and Bax to Induce Nuclear Translocation of Apoptosis-Inducing Factor and Mitochondrial Release of Cytochrome c after Spinal Cord Injury. Journal of Neurotrauma 2009; 26(-7-):965-977. >>> Methylisothiourea, S-; PTIO, carboxy-; Coenzyme Q10; tempol; FeTMPyP; furosemide; PJ-34; CSF, artificial; sesame oil; CSF/CNS (spinal cord); Rat; 1003D; Controls received mp w/ vehicle; multiple pumps per animal (2); post op. care (procraine penicillin); adult, male, specific pathogen free, 200-250 g.); spinal cord injury; PE-10 catheter used; PTIO is a NO trapping agent; enzyme inhibitor PJ-34 is poly(ADP-ribose) polymerase PARP inhibitor.

4892 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;; 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

9568 Tian, Y.H., Lee, K.W., You, I.J., Lee, S.Y., Jang, C.G. 7-nitroindazole, nitric oxide synthase inhibitor, attenuates physical dependence on Butorphanol in rat. Synapse 2008; 62(-8-):582-589. >>> Butorphanol tartrate; nitroindazole, 7-; Saline; DMSO; CSF/CNS; Rat; 2001; Enzyme inhibitor (nitric oxide synthase, NOS); animal info (male, Sprague Dawley, 250-275 g.); pump connected to catheter after 1 week recovery period; 10% DMSO used; PE60 tubing used.

8605 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; Controls received mp w/ vehicle; animal info (male, Wistar, Albino, 250-280g.); 20% DMSO.

7287 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; Controls received mp w/ saline; enzyme inhibitor (nitric oxide synthase); cyanoacrylate adhesive.

3600 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; dose-response; microdialysis; quinolinic acid administered alone or w/1 other agent in same pump; enzyme inhibitor; nitric oxide synthase inhibitor;.

3552 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; 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-

3600 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; 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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“The measurement of substrate flux utilization is based on the novel use of the (ALZET) miniosmotic pump to supply a continuous infusion of one of three tracers... Xu et al., The Journal of Biological Chemistry 2002;277(52):50237-50244.