Role of cGMP versus 20-HETE in the vasodilator response to nitric oxide in rat cerebral arteries

Cheng Wen Sun, J R Falck, Hirotsugu Okamoto, David R. Harder, Richard J. Roman

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

This study examined the response to nitric oxide (NO) in rat middle cerebral arteries (MCA). NO donors increased the activity of a 205-pS K+ channel recorded from vascular smooth muscle (VSM) cells isolated from MCA 10-fold. Blockade of guanylyl cyclase activity with 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10-5 M) did not alter the effect of NO on this channel. In contrast, adding 20-hydroxyeicosatetraenoic acid (20-HETE) to the bath (10-7 M) abolished the response to NO. NO donors also increased the diameter of serotonin-preconstricted MCA to 85% of control. Blockade of K+ channels with iberiotoxin or a high-K+ medium reduced this response by 50%. ODQ (10-5 M) reduced this response by 47 ± 3%, whereas preventing the fall of 20-HETE levels reduced the response by 59 ± 2% (n = 5). Blockade of both pathways eliminated the response to NO donors. These resuits indicate that activation of K+ channels contributes 50% to vasodilator response to NO in rat MCA. This is mediated by a fall in 20-HETE levels rather than a rise in cGMp levels or a direct effect of NO.

Original languageEnglish (US)
Pages (from-to)H339-H350
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number1 48-1
DOIs
StatePublished - 2000

Keywords

  • 20-Hydroxyeicosatetraenoic acid
  • Cerebral circulation
  • Cytochrome P-450
  • Potassium ion channels
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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