Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses

J. P. Tolins, R. M.J. Palmer, S. Moncada, L. Raij

Research output: Contribution to journalArticlepeer-review

280 Scopus citations

Abstract

An endothelium-derived relaxing factor (EDRF) has recently been identified as nitric oxide (NO), originating from endothelial cell metabolism of L-arginine. In vitro studies suggest that EDRF/NO stimulates soluble guanylate cyclase and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels in vascular smooth muscle cells, resulting in the vasorelaxant effects of endothelium-dependent vasodilators such as acetylcholine (ACh). The importance of EDRF/NO in normal physiology or disease states remains uncertain. We therefore investigated the relationship between ACh-induced hemodynamic responses, synthesis of EDRF/NO, and changes in the rate of urinary cGMP excretion in the anesthetized rat in vivo. Intravenous infusion of ACh resulted in hypotension, maintenance of glomerular filtration rate, and renal vasodilatation. ACh induced a dose-dependent increase in urinary cGMP excretion, an effect that was not observed with equihypotensive doses of the endothelium-independent vasodilator, prostacyclin. Rates of cGMP excretion were significantly correlated with the fall in systemic blood pressure induced by ACh. Treatment with N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of enzymatic synthesis of nitric oxide from L-arginine, prevented the ACh-induced increase in urinary cGMP excretion as well as the systemic and renal hemodynamic effects of ACH. Plasma levels of atrial natriuretic peptide were unchanged by ACh infusion. Intravenous infusion of L-NMMA was associated with increased blood pressure and decreased basal rates of urinary cGMP excretion. This hypertensive effect was reversed by administration of L-arginine. We conclude that 1) EDRF/NO mediates the hemodynamic effects of ACh in vivo; 2) urinary excretion of cGMP is a biological marker of EDRF/NO activity; and 3) basal production of EDRF/NO may play a role in regulation of systemic blood pressure and renal hemodynamics.

Original languageEnglish (US)
Pages (from-to)H655-H662
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume258
Issue number3 27-3
DOIs
StatePublished - Jan 1 1990

Keywords

  • guanosine 3',5'-cyclic monophosphate
  • L-arginine
  • L-N(G)-monomethylarginine
  • nitric oxide
  • prostacyclin
  • vascular endothelium

ASJC Scopus subject areas

  • Physiology

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