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. 1990 Jan;99(1):77–86. doi: 10.1111/j.1476-5381.1990.tb14657.x

Effects of basal and acetylcholine-induced release of endothelium-derived relaxing factor on contraction to alpha-adrenoceptor agonists in a rabbit artery and corresponding veins.

J C McGrath 1, S Monaghan 1, A G Templeton 1, V G Wilson 1
PMCID: PMC1917498  PMID: 1970495

Abstract

1. The effects of an endothelium-dependent (acetylcholine) and an endothelium-independent (sodium nitroprusside) relaxant against noradrenaline-induced contractions were compared in three isolated superficial blood vessels of the rabbit, the lateral saphenous vein, plantaris vein and distal saphenous artery. Both produced concentration-related relaxations of all three vessels and were more effective against submaximal than maximal contractions to noradrenaline. Transient contractions to high concentration of acetylcholine occurred only in endothelium-intact preparations of saphenous vein and were inhibited by flurbiprofen. 2. In endothelium-denuded preparations sodium nitroprusside was 3 times more effective than in endothelium-intact preparations, while acetylcholine (less than 3 microM) was inactive. Sensitivity was similar for each relaxant: lateral saphenous vein greater than or equal to plantaris vein greater than distal saphenous artery. The similar profile of sodium nitroprusside and acetylcholine suggests that differences in susceptibility to endothelium-derived relaxing factor (EDRF) are caused by inter-vessel variations in the excitation-coupling process for noradrenaline. 3. Haemoglobin inhibited acetylcholine-induced relaxations in the endothelium-intact preparation of the lateral saphenous vein and distal saphenous artery, which suggests a similar EDRF in each preparation and the likelihood that this is a single substance, presumably nitric oxide. 4. The influence of basal, spontaneously released EDRF on alpha-adrenoceptor function was tested either by mechanical disruption of the endothelium or by adding haemoglobin to endothelium-intact segments. Endothelial disruption slightly reduced contractions to noradrenaline (NA) in distal saphenous artery but increased response size of lateral saphenous and plantaris veins, in the latter also increasing sensitivity to NA: haemoglobin mimicked endothelial disruption. Thus, basal release of EDRF like acetylcholine and nitroprusside was more effective in the veins than in the corresponding artery. 5. In lateral saphenous vein responses to phenylephrine were enhanced by endothelial disruption, but without change in sensitivity: responses to UK-14304, B-HT 920 and cirazoline, which had a relatively slow speed of onset of contraction were not affected. There was no correlation between enhancement and alpha-adrenoceptor sub-type although the agonists which were enhanced all activate alpha 1-adrenoceptors. Competitive antagonists failed to reveal an alpha-adrenoceptor subtype enhanced by endothelial disruption. However, effects of phenoxybenzamine suggest that alpha 1-adrenoceptors are necessary for the influence of basal EDRF.

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Selected References

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  1. Alheid U., Dudel C., Förstermann U. Selective inhibition by gossypol of endothelium-dependent relaxations augments relaxations to glyceryl trinitrate in rabbit coeliac artery. Br J Pharmacol. 1987 Sep;92(1):237–240. doi: 10.1111/j.1476-5381.1987.tb11317.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bullock G. R., Taylor S. G., Weston A. H. Influence of the vascular endothelium on agonist-induced contractions and relaxations in rat aorta. Br J Pharmacol. 1986 Dec;89(4):819–830. doi: 10.1111/j.1476-5381.1986.tb11187.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Butler M., Jenkinson D. H. Blockade by WB 4101 of alpha-adrenoceptors in the rat vas deferens and guinea-pig taenia caeci. Eur J Pharmacol. 1978 Dec 1;52(3-4):303–311. doi: 10.1016/0014-2999(78)90283-2. [DOI] [PubMed] [Google Scholar]
  4. Cambridge D. UK-14,304, a potent and selective alpha2-agonist for the characterisation of alpha-adrenoceptor subtypes. Eur J Pharmacol. 1981 Jul 10;72(4):413–415. doi: 10.1016/0014-2999(81)90588-4. [DOI] [PubMed] [Google Scholar]
  5. Daly C. J., Dunn W. R., McGrath J. C., Wilson V. G. An attempt at selective protection from phenoxybenzamine of postjunctional alpha-adrenoceptor subtypes mediating contractions to noradrenaline in the rabbit isolated saphenous vein. Br J Pharmacol. 1988 Oct;95(2):501–511. doi: 10.1111/j.1476-5381.1988.tb11670.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Daly C. J., McGrath J. C., Wilson V. G. An examination of the postjunctional alpha-adrenoceptor subtypes for (-)-noradrenaline in several isolated blood vessels from the rabbit. Br J Pharmacol. 1988 Oct;95(2):473–484. doi: 10.1111/j.1476-5381.1988.tb11668.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Daly C. J., McGrath J. C., Wilson V. G. Pharmacological analysis of postjunctional alpha-adrenoceptors mediating contractions to (-)-noradrenaline in the rabbit isolated lateral saphenous vein can be explained by interacting responses to simultaneous activation of alpha 1- and alpha 2-adrenoceptors. Br J Pharmacol. 1988 Oct;95(2):485–500. doi: 10.1111/j.1476-5381.1988.tb11669.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. De Mey J. G., Vanhoutte P. M. Heterogeneous behavior of the canine arterial and venous wall. Importance of the endothelium. Circ Res. 1982 Oct;51(4):439–447. doi: 10.1161/01.res.51.4.439. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Godfraind T., Egleme C., Al Osachie I. Role of endothelium in the contractile response of rat aorta to alpha-adrenoceptor agonists. Clin Sci (Lond) 1985;68 (Suppl 10):65s–71s. doi: 10.1042/cs068s065. [DOI] [PubMed] [Google Scholar]
  11. Griffith T. M., Edwards D. H., Davies R. L., Harrison T. J., Evans K. T. EDRF coordinates the behaviour of vascular resistance vessels. Nature. 1987 Oct 1;329(6138):442–445. doi: 10.1038/329442a0. [DOI] [PubMed] [Google Scholar]
  12. Ignarro L. J., Byrns R. E., Buga G. M., Wood K. S. Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. Circ Res. 1987 Dec;61(6):866–879. doi: 10.1161/01.res.61.6.866. [DOI] [PubMed] [Google Scholar]
  13. Ignarro L. J., Byrns R. E., Wood K. S. Endothelium-dependent modulation of cGMP levels and intrinsic smooth muscle tone in isolated bovine intrapulmonary artery and vein. Circ Res. 1987 Jan;60(1):82–92. doi: 10.1161/01.res.60.1.82. [DOI] [PubMed] [Google Scholar]
  14. Ignarro L. J., Kadowitz P. J. The pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Annu Rev Pharmacol Toxicol. 1985;25:171–191. doi: 10.1146/annurev.pa.25.040185.001131. [DOI] [PubMed] [Google Scholar]
  15. Kobinger W., Pichler L. alpha 2-Adrenoceptor agonistic effect of B-HT 920 in isolated perfused hindquarters of rats. Eur J Pharmacol. 1981 Nov 19;76(1):101–105. doi: 10.1016/0014-2999(81)90016-9. [DOI] [PubMed] [Google Scholar]
  16. Lues I., Schümann H. J. Effect of removing the endothelial cells on the reactivity of rat aortic segments to different alpha-adrenoceptor agonists. Naunyn Schmiedebergs Arch Pharmacol. 1984 Dec;328(2):160–163. doi: 10.1007/BF00512066. [DOI] [PubMed] [Google Scholar]
  17. Martin W., Furchgott R. F., Villani G. M., Jothianandan D. Depression of contractile responses in rat aorta by spontaneously released endothelium-derived relaxing factor. J Pharmacol Exp Ther. 1986 May;237(2):529–538. [PubMed] [Google Scholar]
  18. Martin W., Smith J. A., White D. G. The mechanisms by which haemoglobin inhibits the relaxation of rabbit aorta induced by nitrovasodilators, nitric oxide, or bovine retractor penis inhibitory factor. Br J Pharmacol. 1986 Nov;89(3):563–571. doi: 10.1111/j.1476-5381.1986.tb11157.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985 Mar;232(3):708–716. [PubMed] [Google Scholar]
  20. McGrath J. C., Brown C. M., Wilson V. G. Alpha-adrenoceptors: a critical review. Med Res Rev. 1989 Oct-Dec;9(4):407–533. doi: 10.1002/med.2610090403. [DOI] [PubMed] [Google Scholar]
  21. McGrath J. C. Evidence for more than one type of post-junctional alpha-adrenoceptor. Biochem Pharmacol. 1982 Feb 15;31(4):467–484. doi: 10.1016/0006-2952(82)90147-2. [DOI] [PubMed] [Google Scholar]
  22. McGrath J. C., O'Brien J. W. Blockade by nifedipine of responses to intravenous bolus injection or infusion of alpha 1- and alpha 2-adrenoceptor agonists in the pithed rat. Br J Pharmacol. 1987 Jun;91(2):355–365. doi: 10.1111/j.1476-5381.1987.tb10290.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Miller V. M., Vanhoutte P. M. Endothelial alpha 2-adrenoceptors in canine pulmonary and systemic blood vessels. Eur J Pharmacol. 1985 Nov 26;118(1-2):123–129. doi: 10.1016/0014-2999(85)90670-3. [DOI] [PubMed] [Google Scholar]
  24. O'Brien J. W., Flavahan N. A., Grant T. L., McGrath J. C., Marshall R. J. Influence of blood gases, Ca2+-entry blockade and angiotensin converting enzyme inhibition on pressor responses to alpha-adrenoceptor agonists: evidence in vivo for subtypes of response independent of receptor subtype? Clin Sci (Lond) 1985;68 (Suppl 10):99s–104s. doi: 10.1042/cs068s099. [DOI] [PubMed] [Google Scholar]
  25. Oriowo M. A., Bevan J. A., Bevan R. D. Variation in sensitivity of alpha adrenoceptor-mediated contraction of the vascular smooth muscle of rabbit elastic and muscular arteries is related to receptor affinity. J Pharmacol Exp Ther. 1987 Apr;241(1):239–244. [PubMed] [Google Scholar]
  26. Owen M. P., Bevan J. A. Acetylcholine induced endothelial-dependent vasodilation increases as artery diameter decreases in the rabbit ear. Experientia. 1985 Aug 15;41(8):1057–1058. doi: 10.1007/BF01952142. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Randall M. D., Hiley C. R. Detergent and methylene blue affect endothelium-dependent vasorelaxation and pressure/flow relations in rat blood perfused mesenteric arterial bed. Br J Pharmacol. 1988 Dec;95(4):1081–1088. doi: 10.1111/j.1476-5381.1988.tb11742.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rubanyi G. M., Vanhoutte P. M. Heterogeneity of endothelium-dependent responses to acetylcholine in canine femoral arteries and veins. Separation of the role played by endothelial and smooth muscle cells. Blood Vessels. 1988;25(2):75–81. [PubMed] [Google Scholar]
  30. Rubanyi G. M., Vanhoutte P. M. Nature of endothelium-derived relaxing factor: are there two relaxing mediators? Circ Res. 1987 Nov;61(5 Pt 2):II61–II67. [PubMed] [Google Scholar]
  31. Ruffolo R. R., Jr, Waddell J. E. Receptor interactions of imidazolines. IX. Cirazoline is an alpha-1 adrenergic agonist and an alpha-2 adrenergic antagonist. J Pharmacol Exp Ther. 1982 Jul;222(1):29–36. [PubMed] [Google Scholar]
  32. Schümann H. J., Lues I. Postjunctional alpha-adrenoceptors in the isolated saphenous vein of the rabbit. Characterization and influence of angiotensin. Naunyn Schmiedebergs Arch Pharmacol. 1983 Aug;323(4):328–334. doi: 10.1007/BF00512471. [DOI] [PubMed] [Google Scholar]
  33. Seidel C. L., LaRochelle J. Venous and arterial endothelia: different dilator abilities in dog vessels. Circ Res. 1987 Apr;60(4):626–630. doi: 10.1161/01.res.60.4.626. [DOI] [PubMed] [Google Scholar]
  34. Verrecchia C., Sercombe R., Seylaz J. Influence of endothelium on noradrenaline-induced vasoconstriction in rabbit central ear artery. Clin Exp Pharmacol Physiol. 1985 Mar-Apr;12(2):169–179. doi: 10.1111/j.1440-1681.1985.tb02320.x. [DOI] [PubMed] [Google Scholar]
  35. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]

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