The vasorelaxation of cerebral arteries by carbon monoxide.
Carbon monoxide (CO) is known to increase cerebral blood flow, but the effect of CO on the vascular tone of large cerebral arteries is uncertain. We tested whether CO affects cerebral artery tone by measuring tension generated by ex vivo segments of dog basilar artery upon exposure to CO. In cerebral artery segments contracted with either KCl or prostaglandin F(2alpha), CO caused a concentration-related relaxation beginning with a concentration of 57 microM. Relaxation did not occur if CO was administered in the presence of bubbling carboxygen (95% O(2):5% CO(2)), which reduces greater than 99% of CO from the solution. Furthermore, the CO-induced relaxation of cerebral artery segments was reduced in the presence of the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM)or the potassium channel blocker tetraethylammonium (TEA, 1 mM). Neither ODQ nor TEA completely eliminated the relaxation caused by CO and there was no additive effect if ODQ and TEA were administered together. These results suggest that cerebral arteries are directly relaxed by CO and that this relaxation depends upon the activation of guanylyl cyclase and the opening of potassium channels.
Komuro
T
T
Section of Neurosurgery, Department of Surgery, The University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Borsody
M K
MK
Ono
S
S
Marton
L S
LS
Weir
B K
BK
Zhang
Z D
ZD
Paik
E
E
Macdonald
R L
RL
D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D010069:Oxadiazoles / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011189:Potassium Chloride / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D019789:Tetraethylammonium; D011189:Potassium Chloride; D002248:Carbon Monoxide; D015237:Dinoprost; D006162:Guanylate Cyclase