Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Jul;118(6):1518–1522. doi: 10.1111/j.1476-5381.1996.tb15568.x

The involvement of the endothelium in the relaxation of the leopard frog (Rana pipiens) aorta in response to acetylcholine.

G E Knight 1, G Burnstock 1
PMCID: PMC1909655  PMID: 8832080

Abstract

1. The vasodilator response to acetylcholine (ACh) was investigated in the aortic arches of the leopard frog (Rana pipiens). 2. With adrenaline pre-constricted preparations, both ACh and sodium nitroprusside (SNP) caused concentration-dependent relaxations. Damage to the endothelial layer abolished relaxations to ACh, or reduced them greatly, but had no effect on vasodilatation to SNP. 3. NG-Nitro-L-arginine methyl ester (L-NAME; 1-100 microM) concentration-dependently inhibited relaxations in response to ACh, but had no effect on the ability of SNP to induce vasodilatation. 4. L-Arginine (L-Arg; 100-200 times the concentration of L-NAME) failed to reverse the inhibitory effect of L-NAME (1-100 microM) apart from one isolated instance. 5. In summary, this study has shown endothelium-dependent vasodilatation to ACh in an amphibian blood vessel that appears to be mediated via nitric oxide (NO). The response to ACh differs from many mammalian preparations in that the inhibitory effect of L-NAME could not be overcome by L-Arg, in addition to L-NAME itself having no direct effect upon the tone of the vessel.

Full text

PDF
1518

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. Burnstock G. Evolution of the autonomic innervation of visceral and cardiovascular systems in vertebrates. Pharmacol Rev. 1969 Dec;21(4):247–324. [PubMed] [Google Scholar]
  3. Burnstock G., Kirby S. Absence of inhibitory effects of catecholamines on lower vertebrate arterial strip preparations. J Pharm Pharmacol. 1968 May;20(5):404–406. doi: 10.1111/j.2042-7158.1968.tb09773.x. [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. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  7. Gambhir S. S., Das P. K. Cholinergic receptor mechanisms in amphibian vasoconstrictor responses. Pharmacology. 1978;16(2):115–120. doi: 10.1159/000136755. [DOI] [PubMed] [Google Scholar]
  8. Gambhir S. S., Das P. K. Effects of acetylcholine and carbachol on the blood vessels of the frog. Q J Exp Physiol Cogn Med Sci. 1970 Oct;55(4):313–319. doi: 10.1113/expphysiol.1970.sp002083. [DOI] [PubMed] [Google Scholar]
  9. Hasegawa K., Nishimura H. Humoral factor mediates acetylcholine-induced endothelium-dependent relaxation of chicken aorta. Gen Comp Endocrinol. 1991 Oct;84(1):164–169. doi: 10.1016/0016-6480(91)90076-i. [DOI] [PubMed] [Google Scholar]
  10. Holmgren S., Nilsson S. Drug effects on isolated artery strips from two teleosts, Gadus morhua and Salmo gairdneri. Acta Physiol Scand. 1974 Feb;90(2):431–437. doi: 10.1111/j.1748-1716.1974.tb05605.x. [DOI] [PubMed] [Google Scholar]
  11. Ignarro L. J. Biological actions and properties of endothelium-derived nitric oxide formed and released from artery and vein. Circ Res. 1989 Jul;65(1):1–21. doi: 10.1161/01.res.65.1.1. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Ishimatsu A., Johansen K., Nilsson S. Autonomic nervous control of the circulatory system in the air-breathing fish Channa argus. Comp Biochem Physiol C. 1986;84(1):55–60. doi: 10.1016/0742-8413(86)90164-7. [DOI] [PubMed] [Google Scholar]
  15. Jackson W. F., Mülsch A., Busse R. Rhythmic smooth muscle activity in hamster aortas is mediated by continuous release of NO from the endothelium. Am J Physiol. 1991 Jan;260(1 Pt 2):H248–H253. doi: 10.1152/ajpheart.1991.260.1.H248. [DOI] [PubMed] [Google Scholar]
  16. Kirby S., Burnstock G. Pharmacological studies of the cardiovascular system in the anaesthetized sleepy lizard (Tiliqua rugosa) and toad (Bufo marinus). Comp Biochem Physiol. 1969 Jan;28(1):321–331. doi: 10.1016/0010-406x(69)91346-2. [DOI] [PubMed] [Google Scholar]
  17. Klaverkamp J. F., Dyer D. C. Autonomic receptors in isolated rainbow trout vasculature. Eur J Pharmacol. 1974 Sep;28(1):25–34. doi: 10.1016/0014-2999(74)90108-3. [DOI] [PubMed] [Google Scholar]
  18. Lamontagne D., Pohl U., Busse R. NG-nitro-L-arginine antagonizes endothelium-dependent dilator responses by inhibiting endothelium-derived relaxing factor release in the isolated rabbit heart. Pflugers Arch. 1991 Apr;418(3):266–270. doi: 10.1007/BF00370525. [DOI] [PubMed] [Google Scholar]
  19. Miller V. M., Vanhoutte P. M. Endothelium-dependent responses in isolated blood vessels of lower vertebrates. Blood Vessels. 1986;23(4-5):225–235. doi: 10.1159/000158643. [DOI] [PubMed] [Google Scholar]
  20. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  21. Moncada S. The 1991 Ulf von Euler Lecture. The L-arginine: nitric oxide pathway. Acta Physiol Scand. 1992 Jul;145(3):201–227. doi: 10.1111/j.1748-1716.1992.tb09359.x. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Nilsson S., Holmgren S., Grove D. J. Effects of drugs and nerve stimulation on the spleen and arteries of two species of dogfish, Scyliorhinus canicula and Squalus acanthias. Acta Physiol Scand. 1975 Nov;95(3):219–230. doi: 10.1111/j.1748-1716.1975.tb10046.x. [DOI] [PubMed] [Google Scholar]
  24. Ogundahunsi O. A., Tayo F. M. Comparative effects of acetylcholine on the reptilian and mammalian aortae. Arch Int Pharmacodyn Ther. 1988 May-Jun;293:127–133. [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. 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]
  28. Randall M. D., Griffith T. M. Differential effects of L-arginine on the inhibition by NG-nitro-L-arginine methyl ester of basal and agonist-stimulated EDRF activity. Br J Pharmacol. 1991 Nov;104(3):743–749. doi: 10.1111/j.1476-5381.1991.tb12498.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Reite O. B. The evolution of vascular smooth muscle responses to histamine and 5-hydroxytryptamine. 3. Manifestation of dual actions of either amine in reptiles. Acta Physiol Scand. 1970 Feb;78(2):213–231. doi: 10.1111/j.1748-1716.1970.tb04657.x. [DOI] [PubMed] [Google Scholar]
  32. Reite O. B. The evolution of vascular smooth muscle responses to histamine and 5-hydroxytryptamine. II. Appearance of inhibitory actions of 5-hydroxytryptamine in amphibians. Acta Physiol Scand. 1969 Sep-Oct;77(1):36–51. doi: 10.1111/j.1748-1716.1969.tb04551.x. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Small S. A., MacDonald C., Farrell A. P. Vascular reactivity of the coronary artery in rainbow trout (Oncorhynchus mykiss). Am J Physiol. 1990 Jun;258(6 Pt 2):R1402–R1410. doi: 10.1152/ajpregu.1990.258.6.R1402. [DOI] [PubMed] [Google Scholar]
  35. Yamaguchi K., Nishimura H. Angiotensin II-induced relaxation of fowl aorta. Am J Physiol. 1988 Oct;255(4 Pt 2):R591–R599. doi: 10.1152/ajpregu.1988.255.4.R591. [DOI] [PubMed] [Google Scholar]

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

RESOURCES