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. 1990 Nov;101(3):632–639. doi: 10.1111/j.1476-5381.1990.tb14132.x

Regional and cardiac haemodynamic responses to glyceryl trinitrate, acetylcholine, bradykinin and endothelin-1 in conscious rats: effects of NG-nitro-L-arginine methyl ester.

S M Gardiner 1, A M Compton 1, P A Kemp 1, T Bennett 1
PMCID: PMC1917737  PMID: 2127552

Abstract

1. Conscious Long Evans rats, chronically instrumented for cardiovascular measurements, were challenged with i.v. bolus doses of glyceryl trinitrate (40 nmol kg-1), acetylcholine (1.2 nmol kg-1), bradykinin (3.2 nmol kg-1), or endothelin-1 (0.25 nmol kg-1). Under control conditions these doses produced similar falls in mean arterial blood pressure (glyceryl trinitrate, -20 +/- 3 mmHg; acetylcholine, -24 +/- 2 mmHg: bradykinin, -21 +/- 3 mmHg; endothelin-1, -25 +/- 3 mmHg), associated with renal, mesenteric and hindquarters vasodilatations (except for endothelin-1 which caused mesenteric vasoconstriction). 2. In the presence of NG-nitro-L-arginine methyl ester (L-NAME, 10 mgkg-1), a potent inhibitor of nitric oxide biosynthesis and endothelium-dependent vasorelaxation in vitro, the hypotensive responses to glyceryl trinitrate, acetylcholine, and endothelin-1 were increased, although that to bradykinin was not. However, comparing the differences between the response to glyceryl trinitrate and that to any other agonist in the absence and presence of L-NAME showed that there were relative attenuations of the hypotensive responses to bradykinin and endothelin-1, but not to acetylcholine, in the presence of L-NAME. 3. This comparative analysis showed that the renal and hindquarters vasodilator responses to bradykinin and endothelin-1 were attenuated in the presence of L-NAME, but the renal, mesenteric and hindquarters vasodilator responses to acetylcholine were not. However, when L-NAME was administered in the presence of pentolinium, captopril and the vasopressin V1-receptor antagonist, d(CH2)5[Tyr-(Et)]DAVP, (to abolish baroreflex and neurohumoral mechanisms), there was attenuation of the renal and mesenteric vasodilator effects of acetylcholine relative to those seen with glyceryl trinitrate.(ABSTRACT TRUNCATED AT 250 WORDS)

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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. Furchgott R. F. Role of endothelium in responses of vascular smooth muscle. Circ Res. 1983 Nov;53(5):557–573. doi: 10.1161/01.res.53.5.557. [DOI] [PubMed] [Google Scholar]
  3. Gardiner S. M., Compton A. M., Bennett T. Effects of indomethacin on the regional haemodynamic responses to low doses of endothelins and sarafotoxin. Br J Pharmacol. 1990 May;100(1):158–162. doi: 10.1111/j.1476-5381.1990.tb12069.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. 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]
  17. Randall M. D., Douglas S. A., Hiley C. R. Vascular activities of endothelin-1 and some alanyl substituted analogues in resistance beds of the rat. Br J Pharmacol. 1989 Oct;98(2):685–699. doi: 10.1111/j.1476-5381.1989.tb12644.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  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. Smith T. L., Hutchins P. M. Central hemodynamics in the developmental stage of spontaneous hypertension in the unanesthetized rat. Hypertension. 1979 Sep-Oct;1(5):508–517. doi: 10.1161/01.hyp.1.5.508. [DOI] [PubMed] [Google Scholar]
  21. Smits J. F., Coleman T. G., Smith T. L., Kasbergen C. M., van Essen H., Struyker-Boudier H. A. Antihypertensive effect of propranolol in conscious spontaneously hypertensive rats: central hemodynamics, plasma volume, and renal function during beta-blockade with propranolol. J Cardiovasc Pharmacol. 1982 Nov-Dec;4(6):903–914. doi: 10.1097/00005344-198211000-00005. [DOI] [PubMed] [Google Scholar]
  22. Tomlinson K. C., Gardiner S. M., Bennett T. Blood pressure in streptozotocin-treated Brattleboro and Long-Evans rats. Am J Physiol. 1990 Apr;258(4 Pt 2):R852–R859. doi: 10.1152/ajpregu.1990.258.4.R852. [DOI] [PubMed] [Google Scholar]
  23. Warner T. D., de Nucci G., Vane J. R. Rat endothelin is a vasodilator in the isolated perfused mesentery of the rat. Eur J Pharmacol. 1989 Jan 17;159(3):325–326. doi: 10.1016/0014-2999(89)90167-2. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. de Nucci G., Thomas R., D'Orleans-Juste P., Antunes E., Walder C., Warner T. D., Vane J. R. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9797–9800. doi: 10.1073/pnas.85.24.9797. [DOI] [PMC free article] [PubMed] [Google Scholar]

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