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
07/19/2000Pubmed ID
10899074DOI
10.1152/ajpheart.2000.279.1.H339Scopus ID
2-s2.0-0033862805 (requires institutional sign-in at Scopus site) 93 CitationsAbstract
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 RJMESH terms used to index this publication - Major topics in bold
AnimalsCerebral 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
