title: Role of cGMP versus 20-HETE in the vasodilator response to nitric oxide in rat cerebral arteries.
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.
authors.affiliation: Department of Physiology and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Sun
authors.forename: J R
authors.initials: JR
authors.lastname: Falck
authors.forename: H
authors.initials: H
authors.lastname: Okamoto
authors.forename: D R
authors.initials: DR
authors.lastname: Harder
authors.forename: R J
authors.initials: RJ
authors.lastname: Roman
mesh_terms: 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
chemical_list: 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