Abstract
1. The effects of NG-nitro-L-arginine (L-NNA) on mean arterial pressure (MAP) and heart rate (HR) were investigated in conscious rats. 2. Intravenous bolus cumulative doses of L-NNA (1-32 mg kg-1) dose-dependently increased MAP. Both mecamylamine and phentolamine increased MAP responses to L-NNA, angiotensin II and methoxamine. Propranolol, reserpine, atropine and captopril did not affect MAP response to L-NNA. 3. A significant negative correlation of HR and MAP responses to L-NNA was obtained in control rats but not in rats pretreated with reserpine or mecamylamine. Significant negative correlations also occurred in the presence of atropine, propranolol, phentolamine or captopril. 4. A single i.v. bolus dose of L-NNA (32 mg kg-1) raised MAP to a peak value of 53 +/- 3 mmHg and the effect lasted more than 2 h; the rise and recovery of MAP were accompanied by significant decrease and increase in HR, respectively. While both phentolamine and mecamylamine increased peak MAP response to L-NNA, mecamylamine abolished the biphasic HR response and phentolamine potentiated the bradycardiac component of HR. 5. Blockade of the autonomic nervous and renin-angiotensin systems did not attenuate the pressor effects of L-NNA. However, the biphasic HR response to L-NNA is mediated via modulation of autonomic nerve activities.
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- Aisaka K., Gross S. S., Griffith O. W., Levi R. NG-methylarginine, an inhibitor of endothelium-derived nitric oxide synthesis, is a potent pressor agent in the guinea pig: does nitric oxide regulate blood pressure in vivo? Biochem Biophys Res Commun. 1989 Apr 28;160(2):881–886. doi: 10.1016/0006-291x(89)92517-5. [DOI] [PubMed] [Google Scholar]
- Gardiner S. M., Compton A. M., Bennett T., Palmer R. M., Moncada S. Control of regional blood flow by endothelium-derived nitric oxide. Hypertension. 1990 May;15(5):486–492. doi: 10.1161/01.hyp.15.5.486. [DOI] [PubMed] [Google Scholar]
- Gardiner S. M., Compton A. M., Bennett T., Palmer R. M., Moncada S. Regional haemodynamic changes during oral ingestion of NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester in conscious Brattleboro rats. Br J Pharmacol. 1990 Sep;101(1):10–12. doi: 10.1111/j.1476-5381.1990.tb12079.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gardiner S. M., Compton A. M., Kemp P. A., Bennett T. Regional and cardiac haemodynamic responses to glyceryl trinitrate, acetylcholine, bradykinin and endothelin-1 in conscious rats: effects of NG-nitro-L-arginine methyl ester. Br J Pharmacol. 1990 Nov;101(3):632–639. doi: 10.1111/j.1476-5381.1990.tb14132.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenberg S. S., Diecke F. P., Peevy K., Tanaka T. P. Release of norepinephrine from adrenergic nerve endings of blood vessels is modulated by endothelium-derived relaxing factor. Am J Hypertens. 1990 Mar;3(3):211–218. doi: 10.1093/ajh/3.3.211. [DOI] [PubMed] [Google Scholar]
- Ignarro L. J., Buga G. M., Wood K. S., Byrns R. E., Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9265–9269. doi: 10.1073/pnas.84.24.9265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ishii K., Chang B., Kerwin J. F., Jr, Huang Z. J., Murad F. N omega-nitro-L-arginine: a potent inhibitor of endothelium-derived relaxing factor formation. Eur J Pharmacol. 1990 Feb 6;176(2):219–223. doi: 10.1016/0014-2999(90)90531-a. [DOI] [PubMed] [Google Scholar]
- Kobayashi Y., Hattori K. Nitroarginine inhibits endothelium-derived relaxation. Jpn J Pharmacol. 1990 Jan;52(1):167–169. doi: 10.1254/jjp.52.167. [DOI] [PubMed] [Google Scholar]
- LUM B. K., RASHLEIGH P. L. Potentiation of vasoactive drugs by ganglionic blocking agents. J Pharmacol Exp Ther. 1961 Apr;132:13–18. [PubMed] [Google Scholar]
- MAWJI S., LOCKETT M. F. Pressor effects of adrenaline, noradrenaline and reflex vasoconstriction sensitised by low concentrations of ganglion blocking drugs. J Pharm Pharmacol. 1963 Jan;15:45–55. doi: 10.1111/j.2042-7158.1963.tb12742.x. [DOI] [PubMed] [Google Scholar]
- Minson R. B., McRitchie R. J., Chalmers J. P. Effects of neuropeptide Y on the heart and circulation of the conscious rabbit. J Cardiovasc Pharmacol. 1989 Nov;14(5):699–706. doi: 10.1097/00005344-198911000-00005. [DOI] [PubMed] [Google Scholar]
- Moore P. K., al-Swayeh O. A., Chong N. W., Evans R. A., Gibson A. L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. Br J Pharmacol. 1990 Feb;99(2):408–412. doi: 10.1111/j.1476-5381.1990.tb14717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mülsch A., Busse R. NG-nitro-L-arginine (N5-[imino(nitroamino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine. Naunyn Schmiedebergs Arch Pharmacol. 1990 Jan-Feb;341(1-2):143–147. doi: 10.1007/BF00195071. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Rees D. D., Ashton D. S., Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun. 1988 Jun 30;153(3):1251–1256. doi: 10.1016/s0006-291x(88)81362-7. [DOI] [PubMed] [Google Scholar]
- Rees D. D., Palmer R. M., Hodson H. F., Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol. 1989 Feb;96(2):418–424. doi: 10.1111/j.1476-5381.1989.tb11833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rees D. D., Palmer R. M., Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci U S A. 1989 May;86(9):3375–3378. doi: 10.1073/pnas.86.9.3375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rees D. D., Palmer R. M., Schulz R., Hodson H. F., Moncada S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 1990 Nov;101(3):746–752. doi: 10.1111/j.1476-5381.1990.tb14151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakuma I., Stuehr D. J., Gross S. S., Nathan C., Levi R. Identification of arginine as a precursor of endothelium-derived relaxing factor. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8664–8667. doi: 10.1073/pnas.85.22.8664. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tabrizchi R., King K. A., Pang C. C. Pressor response to beta 1- and beta 2-blockers in conscious rats treated with phentolamine. Pharmacology. 1988;37(6):385–393. doi: 10.1159/000138493. [DOI] [PubMed] [Google Scholar]
- Vidal M. J., Romero J. C., Vanhoutte P. M. Endothelium-derived relaxing factor inhibits renin release. Eur J Pharmacol. 1988 May 10;149(3):401–402. doi: 10.1016/0014-2999(88)90679-6. [DOI] [PubMed] [Google Scholar]
- Wang Y. X., Pang C. C. Pressor effect of NG-nitro-L-arginine in pentobarbital-anesthetized rats. Life Sci. 1990;47(24):2217–2224. doi: 10.1016/0024-3205(90)90152-h. [DOI] [PubMed] [Google Scholar]
- Whittle B. J., Lopez-Belmonte J., Rees D. D. Modulation of the vasodepressor actions of acetylcholine, bradykinin, substance P and endothelin in the rat by a specific inhibitor of nitric oxide formation. Br J Pharmacol. 1989 Oct;98(2):646–652. doi: 10.1111/j.1476-5381.1989.tb12639.x. [DOI] [PMC free article] [PubMed] [Google Scholar]