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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Jul;103(3):1725–1732. doi: 10.1111/j.1476-5381.1991.tb09854.x

Effects of NG-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, 5'-N-ethylcarboxamidoadenosine or salbutamol in conscious rats.

S M Gardiner 1, P A Kemp 1, T Bennett 1
PMCID: PMC1907790  PMID: 1933136

Abstract

1. Conscious, Long Evans rats (n = 16), chronically instrumented for the measurement of regional haemodynamics were given 3 min, randomized infusions of two doses of sodium nitroprusside (1.5 and 15 micrograms min-1), acetylcholine (0.4 and 4 micrograms min-1), 5'-N-ethylcarboxamidoadenosine (NECA; 45 and 450 ng min-1), and salbutamol (24 and 240 ng min-1) in the absence and in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 1 mg kg-1 h-1), a potent inhibitor of nitric oxide biosynthesis. 2. Sodium nitroprusside caused hyperaemic vasodilatation in the mesenteric, and common carotid vascular beds. These effects were enhanced in the presence of L-NAME, as was the hypotension. 3. Acetylcholine caused hyperaemic vasodilation inp6he renal, internal carotid and common carotid vascular beds. These effects were attenuated in the presence of L-NAME, but the hypotension was unaffected. 4. NECA caused hyperaemic vasodiltation in the renal, mesenteric, hindquarters, internal carotid and common carotid vascular beds. However, only the hindquarters and internal carotid responses were diminished in the presence of L-NAME and the hypotension was unchanged. 5. Salbutamol caused hyperaemic vasodilatation in the hindquarters vascular bed only. This effect was reduced in the presence of L-NAME, but the hypotension was unchanged. 6. The results indicate marked regional variations in the sensitivity of vasodilator responses to L-NAME that can depend on the vasodilator agent chosen and the dose employed. It is clear from these findings also that measurement of mean arterial blood pressure alone cannot provide adequate information on which to judge the involvement of L-NAME-sensitive mechanisms in vasodilator responses in vivo.

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Selected References

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  1. Aisaka K., Gross S. S., Griffith O. W., Levi R. L-arginine availability determines the duration of acetylcholine-induced systemic vasodilation in vivo. Biochem Biophys Res Commun. 1989 Sep 15;163(2):710–717. doi: 10.1016/0006-291x(89)92281-x. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Busse R., Pohl U., Mülsch A., Bassenge E. Modulation of the vasodilator action of SIN-1 by the endothelium. J Cardiovasc Pharmacol. 1989;14 (Suppl 11):S81–S85. doi: 10.1097/00005344-198906152-00015. [DOI] [PubMed] [Google Scholar]
  4. Feng Q., Hedner T. Endothelium-derived relaxing factor (EDRF) and nitric oxide (NO). II. Physiology, pharmacology and pathophysiological implications. Clin Physiol. 1990 Nov;10(6):503–526. doi: 10.1111/j.1475-097x.1990.tb00443.x. [DOI] [PubMed] [Google Scholar]
  5. Flavahan N. A., Vanhoutte P. M. Mechanism underlying the inhibitory interaction between the nitrovasodilator SIN-1 and the endothelium. J Cardiovasc Pharmacol. 1989;14 (Suppl 11):S86–S90. [PubMed] [Google Scholar]
  6. Forster C., Main J. S., Armstrong P. W. Endothelium modulation of the effects of nitroglycerin on blood vessels from dogs with pacing-induced heart failure. Br J Pharmacol. 1990 Sep;101(1):109–114. doi: 10.1111/j.1476-5381.1990.tb12098.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Furchgott R. F., Vanhoutte P. M. Endothelium-derived relaxing and contracting factors. FASEB J. 1989 Jul;3(9):2007–2018. [PubMed] [Google Scholar]
  8. Gardiner S. M., Bennett T. Regional hemodynamic responses to adrenoceptor antagonism in conscious rats. Am J Physiol. 1988 Oct;255(4 Pt 2):H813–H824. doi: 10.1152/ajpheart.1988.255.4.H813. [DOI] [PubMed] [Google Scholar]
  9. Gardiner S. M., Compton A. M., Bennett T., Hartley C. J. Can pulsed Doppler technique measure changes in aortic blood flow in conscious rats? Am J Physiol. 1990 Aug;259(2 Pt 2):H448–H456. doi: 10.1152/ajpheart.1990.259.2.H448. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Gardiner S. M., Compton A. M., Bennett T. Regional haemodynamic effects of endothelin-1 and endothelin-3 in conscious Long Evans and Brattleboro rats. Br J Pharmacol. 1990 Jan;99(1):107–112. doi: 10.1111/j.1476-5381.1990.tb14662.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gardiner S. M., Compton A. M., Bennett T. Regional hemodynamic effects of endothelin-1 in conscious, unrestrained, Wistar rats. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S202–S204. doi: 10.1097/00005344-198900135-00057. [DOI] [PubMed] [Google Scholar]
  13. Haywood J. R., Shaffer R. A., Fastenow C., Fink G. D., Brody M. J. Regional blood flow measurement with pulsed Doppler flowmeter in conscious rat. Am J Physiol. 1981 Aug;241(2):H273–H278. doi: 10.1152/ajpheart.1981.241.2.H273. [DOI] [PubMed] [Google Scholar]
  14. Kamata K., Miyata N., Kasuya Y. Involvement of endothelial cells in relaxation and contraction responses of the aorta to isoproterenol in naive and streptozotocin-induced diabetic rats. J Pharmacol Exp Ther. 1989 Jun;249(3):890–894. [PubMed] [Google Scholar]
  15. Long C. J., Berkowitz B. A. What is the relationship between the endothelium derived relaxant factor and nitric oxide? Life Sci. 1989;45(1):1–14. doi: 10.1016/0024-3205(89)90429-3. [DOI] [PubMed] [Google Scholar]
  16. Lüscher T. F., Richard V., Yang Z. H. Interaction between endothelium-derived nitric oxide and SIN-1 in human and porcine blood vessels. J Cardiovasc Pharmacol. 1989;14 (Suppl 11):S76–S80. [PubMed] [Google Scholar]
  17. Moncada S., Palmer R. M., Higgs E. A. The discovery of nitric oxide as the endogenous nitrovasodilator. Hypertension. 1988 Oct;12(4):365–372. doi: 10.1161/01.hyp.12.4.365. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. Rose'Meyer R. B., Hope W. Evidence that A2 purinoceptors are involved in endothelium-dependent relaxation of the rat thoracic aorta. Br J Pharmacol. 1990 Jul;100(3):576–580. doi: 10.1111/j.1476-5381.1990.tb15849.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rubanyi G., Vanhoutte P. M. Endothelium-removal decreases relaxations of canine coronary arteries caused by beta-adrenergic agonists and adenosine. J Cardiovasc Pharmacol. 1985 Jan-Feb;7(1):139–144. doi: 10.1097/00005344-198501000-00023. [DOI] [PubMed] [Google Scholar]
  23. Shirasaki Y., Su C. Endothelium removal augments vasodilation by sodium nitroprusside and sodium nitrite. Eur J Pharmacol. 1985 Aug 7;114(1):93–96. doi: 10.1016/0014-2999(85)90527-8. [DOI] [PubMed] [Google Scholar]
  24. Theodorsson-Norheim E. Friedman and Quade tests: BASIC computer program to perform nonparametric two-way analysis of variance and multiple comparisons on ranks of several related samples. Comput Biol Med. 1987;17(2):85–99. doi: 10.1016/0010-4825(87)90003-5. [DOI] [PubMed] [Google Scholar]
  25. Thomas G. R., Thiemermann C., Walder C., Vane J. R. The effects of endothelium-dependent vasodilators on cardiac output and their distribution in the anaesthetized rat: a comparison with sodium nitroprusside. Br J Pharmacol. 1988 Nov;95(3):986–992. doi: 10.1111/j.1476-5381.1988.tb11729.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tolins J. P., Palmer R. M., Moncada S., Raij L. Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses. Am J Physiol. 1990 Mar;258(3 Pt 2):H655–H662. doi: 10.1152/ajpheart.1990.258.3.H655. [DOI] [PubMed] [Google Scholar]
  27. Vanhoutte P. M., Levy M. N. Prejunctional cholinergic modulation of adrenergic neurotransmission in the cardiovascular system. Am J Physiol. 1980 Mar;238(3):H275–H281. doi: 10.1152/ajpheart.1980.238.3.H275. [DOI] [PubMed] [Google Scholar]
  28. Walder C. E., Thiemermann C., Vane J. R. The involvement of endothelium-derived relaxing factor in the regulation of renal cortical blood flow in the rat. Br J Pharmacol. 1991 Apr;102(4):967–973. doi: 10.1111/j.1476-5381.1991.tb12285.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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