Nitric oxide-20-hydroxyeicosatetraenoic acid interaction in the regulation of K+ channel activity and vascular tone in renal arterioles

Cheng Wen Sun, Magdalena Alonso-Galicia, M. Reza Taheri, J R Falck, David R. Harder, Richard J. Roman

Research output: Contribution to journalArticle

151 Scopus citations

Abstract

The present study examined whether inhibition of P4504A enzyme activity and the formation of 20-HETE contributes to the activation of K+ channels and vasodilator effects of nitric oxide (NO) in renal arterioles. Addition of an NO donor to the P4504A2 enzyme that produces 20-HETE increased visible light absorbance at 440 nm indicating that NO binds to heme in this enzyme. NO donors also dose-dependently inhibited the formation of 20-HETE in microsomes prepared from renal arterioles. In patch-clamp experiments, NO donors increased the open-state probability of a voltage-sensitive, large- conductance (195±9 pS) K+ channel recorded with cell-attached patches on renal arteriolar smooth muscle cells. Blockade of guanylyl cyclase with [1H- [1,2,4]Oxadiazolo[4,3-a] quinoxalin-1-one] (ODQ, 10 μmol/L), or cGMP- dependent kinase with 8R,9S,11S-(-)-9-methoxycarbamyl-8-methyl-2,3,9,10- tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-trizadibenzo-(a,g)-cy-cloocta- (c,d,e)-trinden-1-one (KT-5823) (1 μmol/L) did not alter the effects of NO on this channel. In contrast, inhibition of the formation of 20-HETE with 17- octadecynoic acid (1 μmol/L) activated this channel and masked the response to NO. Preventing the NO-induced reduction in intracellular 20-HETE levels also blocked the effects of NO on this channel. Sodium nitroprusside (SNP) increased the diameter of renal interlobular arteries preconstricted with phenylephrine to 80±4% of control. Blockade of guanylyl cyclase with ODQ (10 μmol/L) attenuated the response to SNP by 26±2%; however, fixing 20-HETE levels at 100 nmol/L reduced the response by 67±8%. Blockade of both pathways eliminated the response to SNP. These results indicate that inhibition of the formation of 20-HETE contributes to the activation of K+ channels and the vasodilator effects of NO in the renal microcirculation.

Original languageEnglish (US)
Pages (from-to)1069-1079
Number of pages11
JournalCirculation research
Volume83
Issue number11
DOIs
StatePublished - Nov 30 1998

Keywords

  • Arachidonic acid
  • Cytochrome P450
  • Renal circulation vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Nitric oxide-20-hydroxyeicosatetraenoic acid interaction in the regulation of K<sup>+</sup> channel activity and vascular tone in renal arterioles'. Together they form a unique fingerprint.

  • Cite this