Faculty Collaboration Database

Role of cGMP versus 20-HETE in the vasodilator response to nitric oxide in rat cerebral arteries. Am J Physiol Heart Circ Physiol 2000 Jul;279(1):H339-50

Date

07/19/2000

Pubmed ID

10899074

DOI

10.1152/ajpheart.2000.279.1.H339

Scopus ID

2-s2.0-0033862805 (requires institutional sign-in at Scopus site)   94 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 results 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.

Author List

Sun CW, Falck JR, Okamoto H, Harder DR, Roman RJ

Author

David Harder PhD, MS Emeritus Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cerebral Arteries
Cyclic GMP
Enzyme Inhibitors
Guanylate Cyclase
Hydroxyeicosatetraenoic Acids
In Vitro Techniques
Male
Muscle, Smooth, Vascular
Nitric Oxide Donors
Nitroprusside
Oxadiazoles
Patch-Clamp Techniques
Potassium Channels
Quinoxalines
Rats
Rats, Sprague-Dawley
Vasodilation
Vasodilator Agents