Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Jun;103(2):1407–1410. doi: 10.1111/j.1476-5381.1991.tb09802.x

N-nitro L-arginine causes coronary vasoconstriction and inhibits endothelium-dependent vasodilatation in anaesthetized greyhounds.

O L Woodman 1, G J Dusting 1
PMCID: PMC1908370  PMID: 1909199

Abstract

1. The effect of N-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide biosynthesis, on large coronary artery diameter and coronary blood flow was examined in anaesthetized greyhounds. The effects of L-NNA on the coronary vascular responses to acetylcholine (ACh), glyceryl trinitrate (GTN) and 5-hydroxytryptamine (5-HT) were also assessed. 2. L-NNA (5 mg kg-1), infused into the left circumflex coronary artery, increased systemic mean arterial pressure and decreased the external diameter of the artery. Infusion of L-NNA decreased coronary blood flow in 5 of the 7 dogs tested and increased mean coronary resistance but neither of these effects was statistically significant. There was no change in heart rate. 3. Intra-arterial injection of both ACh (0.01-0.05 micrograms kg-1) and GTN (0.1-0.5 micrograms kg-1) increased large coronary artery diameter and coronary blood flow. Coronary vascular responses to the endothelium-dependent vasodilator ACh were significantly reduced by L-NNA, whereas the responses to the endothelium-independent vasodilator GTN were not significantly affected. 4. 5-HT (0.1 microgram kg-1, injected into the left circumflex coronary artery) decreased coronary artery diameter but increased coronary blood flow. After the administration of L-NNA the 5-HT-induced dilatation of the coronary resistance vessels was significantly attenuated whereas the constriction of the circumflex coronary artery was increased in 3 out of 3 dogs in which diameter could be measured, although the latter effect was not statistically significant. 5. These data indicate that L-NNA causes coronary and systemic vasoconstriction and selectively inhibits endothelium-dependent vasodilatation in the coronary circulation of the anaesthetized greyhound.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1407

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amezcua J. L., Palmer R. M., de Souza B. M., Moncada S. Nitric oxide synthesized from L-arginine regulates vascular tone in the coronary circulation of the rabbit. Br J Pharmacol. 1989 Aug;97(4):1119–1124. doi: 10.1111/j.1476-5381.1989.tb12569.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bossaller C., Habib G. B., Yamamoto H., Williams C., Wells S., Henry P. D. Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest. 1987 Jan;79(1):170–174. doi: 10.1172/JCI112779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brum J. M., Sufan Q., Lane G., Bove A. A. Increased vasoconstrictor activity of proximal coronary arteries with endothelial damage in intact dogs. Circulation. 1984 Dec;70(6):1066–1073. doi: 10.1161/01.cir.70.6.1066. [DOI] [PubMed] [Google Scholar]
  4. Cocks T. M., Angus J. A. Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature. 1983 Oct 13;305(5935):627–630. doi: 10.1038/305627a0. [DOI] [PubMed] [Google Scholar]
  5. Cohen R. A., Shepherd J. T., Vanhoutte P. M. 5-Hydroxytryptamine can mediate endothelium-dependent relaxation of coronary arteries. Am J Physiol. 1983 Dec;245(6):H1077–H1080. doi: 10.1152/ajpheart.1983.245.6.H1077. [DOI] [PubMed] [Google Scholar]
  6. Dubbin P. N., Zambetis M., Dusting G. J. Inhibition of endothelial nitric oxide biosynthesis by N-nitro-L-arginine. Clin Exp Pharmacol Physiol. 1990 Apr;17(4):281–286. doi: 10.1111/j.1440-1681.1990.tb01321.x. [DOI] [PubMed] [Google Scholar]
  7. Dusting G. J., Macdonald P. S., Higgs E. A., Moncada S. The endogenous nitrovasodilator produced by the vascular endothelium. Aust N Z J Med. 1989 Oct;19(5):493–498. doi: 10.1111/j.1445-5994.1989.tb00319.x. [DOI] [PubMed] [Google Scholar]
  8. Furchgott R. F. The role of endothelium in the responses of vascular smooth muscle to drugs. Annu Rev Pharmacol Toxicol. 1984;24:175–197. doi: 10.1146/annurev.pa.24.040184.001135. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Habib J. B., Bossaller C., Wells S., Williams C., Morrisett J. D., Henry P. D. Preservation of endothelium-dependent vascular relaxation in cholesterol-fed rabbit by treatment with the calcium blocker PN 200110. Circ Res. 1986 Feb;58(2):305–309. doi: 10.1161/01.res.58.2.305. [DOI] [PubMed] [Google Scholar]
  11. Lamping K. G., Marcus M. L., Dole W. P. Removal of the endothelium potentiates canine large coronary artery constrictor responses to 5-hydroxytryptamine in vivo. Circ Res. 1985 Jul;57(1):46–54. doi: 10.1161/01.res.57.1.46. [DOI] [PubMed] [Google Scholar]
  12. Minson R. B., McRitchie R. J., Chalmers J. P. Effects of neuropeptide Y on baroreflex control of heart rate and myocardial contractility in conscious rabbits. Clin Exp Pharmacol Physiol. 1990 Jan;17(1):39–49. doi: 10.1111/j.1440-1681.1990.tb01263.x. [DOI] [PubMed] [Google Scholar]
  13. Moncada S., Palmer R. M., Higgs E. A. Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol. 1989 Jun 1;38(11):1709–1715. doi: 10.1016/0006-2952(89)90403-6. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Palmer R. M., Ashton D. S., Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664–666. doi: 10.1038/333664a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Vallance P., Collier J., Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet. 1989 Oct 28;2(8670):997–1000. doi: 10.1016/s0140-6736(89)91013-1. [DOI] [PubMed] [Google Scholar]
  18. Verbeuren T. J., Jordaens F. H., Zonnekeyn L. L., Van Hove C. E., Coene M. C., Herman A. G. Effect of hypercholesterolemia on vascular reactivity in the rabbit. I. Endothelium-dependent and endothelium-independent contractions and relaxations in isolated arteries of control and hypercholesterolemic rabbits. Circ Res. 1986 Apr;58(4):552–564. doi: 10.1161/01.res.58.4.552. [DOI] [PubMed] [Google Scholar]
  19. Vita J. A., Treasure C. B., Nabel E. G., McLenachan J. M., Fish R. D., Yeung A. C., Vekshtein V. I., Selwyn A. P., Ganz P. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation. 1990 Feb;81(2):491–497. doi: 10.1161/01.cir.81.2.491. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Woodman O. L. Enhanced coronary vasoconstrictor responses to 5-hydroxytryptamine in the presence of a coronary artery stenosis in anaesthetized dogs. Br J Pharmacol. 1990 May;100(1):153–157. doi: 10.1111/j.1476-5381.1990.tb12068.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yasue H., Matsuyama K., Matsuyama K., Okumura K., Morikami Y., Ogawa H. Responses of angiographically normal human coronary arteries to intracoronary injection of acetylcholine by age and segment. Possible role of early coronary atherosclerosis. Circulation. 1990 Feb;81(2):482–490. doi: 10.1161/01.cir.81.2.482. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES