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. 1993 Sep;92(3):1483–1490. doi: 10.1172/JCI116726

Vasodilatory effect of arginine vasopressin is mediated by nitric oxide in human forearm vessels.

T Tagawa 1, T Imaizumi 1, T Endo 1, M Shiramoto 1, Y Hirooka 1, S Ando 1, A Takeshita 1
PMCID: PMC288294  PMID: 8376600

Abstract

Arginine vasopressin (AVP) causes biphasic changes in vascular resistance in human forearms; vasoconstriction at lower doses and vasodilation at higher doses. Vasoconstriction is mediated by the V1 receptor. However, the mechanism of AVP-induced vasodilation is not known. We investigated whether AVP-induced vasodilation is mediated by nitric oxide (NO) in human forearms by examining the effects of L-arginine (a precursor of NO) and NG-monomethyl-L-arginine (L-NMMA, a blocker of NO synthase) on AVP-induced vasodilation. AVP was infused intraarterially at doses of 0.05, 0.1, 0.2, 0.5, and 1.0 ng/kg per min (n = 8). The lower doses of AVP (< or = 0.1 ng/kg per min) increased, whereas the higher doses of AVP (> or = 0.5 ng/kg per min) decreased forearm vascular resistance (FVR) (P < 0.01). Intraarterially infused L-arginine at 10 mg/min did not alter arterial pressure, baseline FVR, or heart rate. L-arginine did not alter the magnitude of AVP-induced vasoconstriction at the lower doses, but L-arginine augmented the magnitude of AVP-induced vasodilation at doses of 0.2 (P < 0.05), 0.5 (P < 0.01), and 1.0 (P < 0.05) ng/kg per min. In another group (n = 6), intraarterially infused L-NMMA (4 mumol/min for 5 min) increased baseline FVR without systemic effects, and inhibited acetylcholine-induced vasodilation (P < 0.01). L-NMMA at this dose inhibited AVP-induced vasodilation (P < 0.01) but did not affect vasoconstriction. L-arginine reversed the inhibitory effect of L-NMMA. Our results suggest that the vasodilatory effect of AVP may be mediated by NO in human forearms.

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  1. Altura B. M., Altura B. T. Vascular smooth muscle and neurohypophyseal hormones. Fed Proc. 1977 May;36(6):1853–1860. [PubMed] [Google Scholar]
  2. Cowley A. W., Jr, Monos E., Guyton A. C. Interaction of vasopressin and the baroreceptor reflex system in the regulation of arterial blood pressure in the dog. Circ Res. 1974 Apr;34(4):505–514. doi: 10.1161/01.res.34.4.505. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Gryglewski R. J., Botting R. M., Vane J. R. Mediators produced by the endothelial cell. Hypertension. 1988 Dec;12(6):530–548. doi: 10.1161/01.hyp.12.6.530. [DOI] [PubMed] [Google Scholar]
  5. Hirsch A. T., Dzau V. J., Majzoub J. A., Creager M. A. Vasopressin-mediated forearm vasodilation in normal humans. Evidence for a vascular vasopressin V2 receptor. J Clin Invest. 1989 Aug;84(2):418–426. doi: 10.1172/JCI114182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hishikawa K., Nakaki T., Suzuki H., Saruta T., Kato R. L-arginine-induced hypotension. Lancet. 1991 Mar 16;337(8742):683–684. doi: 10.1016/0140-6736(91)92510-9. [DOI] [PubMed] [Google Scholar]
  7. Hishikawa K., Nakaki T., Tsuda M., Esumi H., Ohshima H., Suzuki H., Saruta T., Kato R. Effect of systemic L-arginine administration on hemodynamics and nitric oxide release in man. Jpn Heart J. 1992 Jan;33(1):41–48. doi: 10.1536/ihj.33.41. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Ignarro L. J. Nitric oxide. A novel signal transduction mechanism for transcellular communication. Hypertension. 1990 Nov;16(5):477–483. doi: 10.1161/01.hyp.16.5.477. [DOI] [PubMed] [Google Scholar]
  10. Imaizumi T., Harada S., Hirooka Y., Masaki H., Momohara M., Takeshita A. Effects of OPC-21268, an orally effective vasopressin V1 receptor antagonist in humans. Hypertension. 1992 Jul;20(1):54–58. doi: 10.1161/01.hyp.20.1.54. [DOI] [PubMed] [Google Scholar]
  11. Imaizumi T., Hirooka Y., Masaki H., Harada S., Momohara M., Tagawa T., Takeshita A. Effects of L-arginine on forearm vessels and responses to acetylcholine. Hypertension. 1992 Oct;20(4):511–517. doi: 10.1161/01.hyp.20.4.511. [DOI] [PubMed] [Google Scholar]
  12. Imaizumi T., Takeshita A., Ashihara T., Nakamura M. The effects of sublingually administered nitroglycerin on forearm vascular resistance in patients with heart failure and in normal subjects. Circulation. 1985 Oct;72(4):747–752. doi: 10.1161/01.cir.72.4.747. [DOI] [PubMed] [Google Scholar]
  13. Imaizumi T., Takeshita A., Suzuki S., Yoshida M., Ando S., Nakamura M. Age-independent forearm vasodilatation by acetylcholine and adenosine 5'-triphosphate in humans. Clin Sci (Lond) 1990 Jan;78(1):89–93. doi: 10.1042/cs0780089. [DOI] [PubMed] [Google Scholar]
  14. Imaizumi T., Thames M. D. Influence of intravenous and intracerebroventricular vasopressin on baroreflex control of renal nerve traffic. Circ Res. 1986 Jan;58(1):17–25. doi: 10.1161/01.res.58.1.17. [DOI] [PubMed] [Google Scholar]
  15. KITCHIN A. H. The effect of pitressin on hand and forearm blood flow. Clin Sci. 1957 Nov;16(4):639–644. [PubMed] [Google Scholar]
  16. Katusic Z. S., Shepherd J. T., Vanhoutte P. M. Oxytocin causes endothelium-dependent relaxations of canine basilar arteries by activating V1-vasopressinergic receptors. J Pharmacol Exp Ther. 1986 Jan;236(1):166–170. [PubMed] [Google Scholar]
  17. Katusic Z. S., Shepherd J. T., Vanhoutte P. M. Vasopressin causes endothelium-dependent relaxations of the canine basilar artery. Circ Res. 1984 Nov;55(5):575–579. doi: 10.1161/01.res.55.5.575. [DOI] [PubMed] [Google Scholar]
  18. Kelm M., Schrader J. Control of coronary vascular tone by nitric oxide. Circ Res. 1990 Jun;66(6):1561–1575. doi: 10.1161/01.res.66.6.1561. [DOI] [PubMed] [Google Scholar]
  19. Lee P. L., Slocum R. H. A high-resolution method for amino acid analysis of physiological fluids containing mixed disulfides. Clin Chem. 1988 Apr;34(4):719–723. [PubMed] [Google Scholar]
  20. Mayer B., Schmidt K., Humbert P., Böhme E. Biosynthesis of endothelium-derived relaxing factor: a cytosolic enzyme in porcine aortic endothelial cells Ca2+-dependently converts L-arginine into an activator of soluble guanylyl cyclase. Biochem Biophys Res Commun. 1989 Oct 31;164(2):678–685. doi: 10.1016/0006-291x(89)91513-1. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Montani J. P., Liard J. F., Schoun J., Möhring J. Hemodynamic effects of exogenous and endogenous vasopressin at low plasma concentrations in conscious dogs. Circ Res. 1980 Sep;47(3):346–355. doi: 10.1161/01.res.47.3.346. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Palmer R. M., Moncada S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun. 1989 Jan 16;158(1):348–352. doi: 10.1016/s0006-291x(89)80219-0. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Schini V. B., Katusic Z. S., Vanhoutte P. M. Neurohypophyseal peptides and tachykinins stimulate the production of cyclic GMP in cultured porcine aortic endothelial cells. J Pharmacol Exp Ther. 1990 Dec;255(3):994–1000. [PubMed] [Google Scholar]
  28. Share L. Role of vasopressin in cardiovascular regulation. Physiol Rev. 1988 Oct;68(4):1248–1284. doi: 10.1152/physrev.1988.68.4.1248. [DOI] [PubMed] [Google Scholar]
  29. Share L. Role of vasopressin in cardiovascular regulation. Physiol Rev. 1988 Oct;68(4):1248–1284. doi: 10.1152/physrev.1988.68.4.1248. [DOI] [PubMed] [Google Scholar]
  30. Suzuki S., Takeshita A., Imaizumi T., Hirooka Y., Yoshida M., Ando S., Nakamura M. Biphasic forearm vascular responses to intraarterial arginine vasopressin. J Clin Invest. 1989 Aug;84(2):427–434. doi: 10.1172/JCI114183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Suzuki S., Takeshita A., Imaizumi T., Hirooka Y., Yoshida M., Ando S., Nakamura M. Central nervous system mechanisms involved in inhibition of renal sympathetic nerve activity induced by arginine vasopressin. Circ Res. 1989 Nov;65(5):1390–1399. doi: 10.1161/01.res.65.5.1390. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Vanhoutte P. M. Endothelium and control of vascular function. State of the Art lecture. Hypertension. 1989 Jun;13(6 Pt 2):658–667. doi: 10.1161/01.hyp.13.6.658. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Walker B. R. Evidence for a vasodilatory effect of vasopressin in the conscious rat. Am J Physiol. 1986 Jul;251(1 Pt 2):H34–H39. doi: 10.1152/ajpheart.1986.251.1.H34. [DOI] [PubMed] [Google Scholar]
  36. Watabe T., Tanaka K., Kumagae M., Itoh S., Kogure M., Hasegawa M., Horiuchi T., Morio K., Takeda F., Ubukata E. Role of endogenous arginine vasopressin in potentiating corticotropin-releasing hormone-stimulated corticotropin secretion in man. J Clin Endocrinol Metab. 1988 Jun;66(6):1132–1137. doi: 10.1210/jcem-66-6-1132. [DOI] [PubMed] [Google Scholar]
  37. Watabe T., Tanaka K., Kumagae M., Itoh S., Takeda F., Morio K., Hasegawa M., Horiuchi T., Miyabe S., Shimizu N. Hormonal responses to insulin-induced hypoglycemia in man. J Clin Endocrinol Metab. 1987 Dec;65(6):1187–1191. doi: 10.1210/jcem-65-6-1187. [DOI] [PubMed] [Google Scholar]

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