Adenosine and hypoxic dilation of rat coronary small arteries: roles of the ATP-sensitive potassium channel, endothelium, and nitric oxide.
The aims of the study were to examine the roles of the ATP-sensitive potassium (K(ATP)) channel, the endothelium, and nitric oxide (NO) in the responses of rat coronary small arteries to adenosine and hypoxia. Segments of rat coronary vessel were investigated in vitro using pressure myography; all vessels studied developed stable spontaneous myogenic tone during equilibration. Glibenclamide (a K(ATP) channel inhibitor) reversed pinacidil but not 2-deoxyglucose-induced dilation. Both adenosine and hypoxia dilated the vessels, and glibenclamide did not reverse these responses. Endothelial removal or N(G)-nitro-L-arginine methyl ester (L-NAME) inhibited the dilation to adenosine by approximately 50%; subsequent addition of glibenclamide was without effect. Hypoxic dilation was completely inhibited by endothelium removal or L-NAME. We conclude that adenosine- and hypoxia-induced dilation of rat coronary arteries does not appear to involve the K(ATP) channel. Adenosine-induced dilation is partially and hypoxic dilation is completely dependent on endothelium-derived NO.
Lynch
F M
FM
Cardiovascular Research Group, Department of Medicine, Manchester Royal Infirmary, Oxford Rd., Manchester M13 9WL, United Kingdom.
Austin
C
C
Heagerty
A M
AM
Izzard
A S
AS
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D009569:Nitric Oxide; D000241:Adenosine