Dilation of rat brain arterioles by hypercapnia in vivo can occur even after blockade of guanylate cyclase by ODQ.
1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) is an inhibitor of guanylate cyclase and has been reported to inhibit dilation of cerebral blood vessels by hypercapnia. This supports the hypothesis that this dilation is dependent upon guanylate cyclase, activated by nitric oxide (NO) released from neural tissue. However, there are conflicting reports concerning the role of guanylate cyclase in response to hypercapnia. Therefore, we tested the effect of topically applied ODQ (10 microM) on rat pial arterioles observed with a microscope through a closed cranial window. In one study, we tested ODQ ability to inhibit both the dilation produced by hypercapnia (3% and 5% inspired CO(2)) and, in the same rats, the dilation produced by N-methyl-D-aspartate (NMDA). In another experiment, we tested the ability of ODQ to inhibit dilation produced by hypercapnia and the dilation produced by 3-morpholinosydnonimine (SIN-1), a donor of NO. The responses to NMDA and to NO are known to depend upon activation of guanylate cyclase and were both blocked in the present study. However, the response to hypercapnia was not affected. These findings provide evidence that hypercapnic dilation can occur independently of guanylate cyclase activation.
Rosenblum
William I
WI
Department of Pathology (Neuropathology), Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, VA 23298-0017, USA. wirosenb@aol.com
Wei
Enoch P
EP
Kontos
Hermes A
HA
D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000201:enzymology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006935:Hypercapnia / Q000201:enzymology*; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D006162:Guanylate Cyclase