Enhancement of the vasodepressor response to adenosine by nicorandil in rats: comparison with cromakalim.
The effect of nicorandil on systemic blood pressure (SBP) and heart rate (HR) responses to adenosine was compared with that of cromakalim, an adenosine triphosphate (ATP)-sensitive K+ channel opener, in anesthetized rats. Intravenous (i.v.) adenosine in doses of 1-100 micrograms/kg elicited dose-dependent decreases in SBP, accompanied by decreases in HR. Potentiation of adenosine action by i.v. infusion of either nicorandil (10 or 30 micrograms/kg per min) or cromakalim (0.1 microgram/kg per min) occurred in all of the animals tested. After i.v. treatment with glibenclamide (20 mg/kg), an ATP-sensitive K+ channel blocker, not only adenosine action but also the enhancement of adenosine action by nicorandil and cromakalim were significantly attenuated. The present result indicates that the enhancement of the adenosine action by nicorandil and cromakalim appears to occur at least partly through ATP-sensitive K+ channel activation.
Saito
K
K
Central Research Laboratories, Chugai Pharmaceutical Co, Ltd., Tokyo, Japan.
Sakai
K
K
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D019806:Cromakalim / Q000494:pharmacology*; D004357:Drug Synergism; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D000255:Adenosine Triphosphate; D000241:Adenosine; D005905:Glyburide