Contribution of 20-HETE to the vasodilator actions of nitric oxide in renal arteries

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

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89 Scopus citations


The present study examined the contribution of elevations in cGMP versus inhibition of cytochrome P-4504A enzymes and the production of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) to the vasodilator actions of NO in renal arterioles. The NO donor sodium nitroprusside (SNP) at 10-5, 10-4, and 10-3 M reduced the production of 20-HETE in microsomes prepared from renal arterioles to 80 ± 2, 43 ± 5, and 7 ± 1% of control, respectively (n = 4). In other experiments, the vasodilator response to SNP (10-7 to 10-3 M) was examined in rat renal interlobular arteries (<90 μm ID), preconstricted with phenylephrine (1 μM) under control conditions and after blockade of the cGMP and P-4504A pathways. Inhibition of guanylyl cyclase with 1H-[1,2,4]oxadiazole[4,3-α]quinoxalin-1-one (ODQ) (10 μM, n = 6) or of cGMP-dependent protein kinase with 8R,9S,11S-(-)-9-methoxy-carbamyl- 8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11α-trizadibenzo- (α,g)-cycloocta-(c,d,e)-trinden-1-one (KT-5823, 1 μM; n = 5) attenuated the vasodilator response to SNP by 26 and 30%, respectively. In contrast, inhibition of the endogenous production of 20-HETE with a suicide substrate, irreversible inhibitor [17-octadecynoic acid (17-ODYA), 1 μM, n = 5], or a selective, competitive inhibitor of 20-HETE formation (dibromo-dodecenyl- methylsulfimide, 25 μM, n = 5) markedly impaired the vasodilator response to SNP by 76 and 78%, respectively. Similarly, when 20-HETE levels were fixed at 100 nM (n = 6), the response to SNP was attenuated by 73%. Blockade of both pathways with ODQ and 17-ODYA completely abolished the response to SNP (n = 6). These results indicate that the vasodilator response to NO is largely cGMP independent and that inhibition of 20-HETE formation contributes to the cGMP-independent effects of NO in the renal microcirculation.

Original languageEnglish (US)
Pages (from-to)F370-F378
JournalAmerican Journal of Physiology - Renal Physiology
Issue number3 44-3
StatePublished - Sep 1998


  • Arachidonic acid
  • Cytochrome P-450 enzymes
  • Guanosine 3',5'-cyclic monophosphate
  • Potassium channels
  • Renal circulation

ASJC Scopus subject areas

  • Physiology
  • Urology


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