Role of cGMP versus 20-HETE in the vasodilator response to nitric oxide in rat cerebral arteries.
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.
Sun
C W
CW
Department of Physiology and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Falck
J R
JR
Okamoto
H
H
Harder
D R
DR
Roman
R J
RJ
D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D015221:Potassium Channels; D011810:Quinoxalines; D014665:Vasodilator Agents; D009599:Nitroprusside; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D006162:Guanylate Cyclase; D006152:Cyclic GMP