Potentiating effect of nicorandil on the adenosine A2 receptor-mediated vasodepression in rats: potential role for KATP channels.
The effects of nicorandil on systemic blood pressure (SBP) and heart rate (HR) responses to adenosine were compared with those to N6-cyclopentyladenosine (CPA), a selective adenosine A1 receptor agonist, and 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), a selective adenosine A2 receptor agonist, in anesthetized rats. When injected intravenously (i.v.), single bolus doses of CPCA (0.01-1.0 micrograms/kg), like adenosine (30 micrograms/kg), elicited dose-dependent decreases in SBP scarcely affecting HR, while CPA (0.03-1.0 micrograms/kg) produced only reduction of HR without influencing SBP. The enhancement of the vasodepressor response to CPCA, like adenosine, was induced by the i.v. infusion of either nicorandil (10 micrograms/kg per min) or cromakalim (0.1 micrograms/kg per min), but the response to CPA in HR remained unmodified during the infusion of nicorandil as well as cromakalim. After i.v. treatment with glibenclamide (20 mg/kg), and adenosine triphosphate (ATP)-sensitive K+ channel blocker, or 3,7-dimethyl-1-propargylxanthine (DMPX) (1 mg/kg), a selective antagonist of adenosine A2 receptor, not only CPCA action but also the enhancement of CPCA action by nicorandil and cromakalim were significantly attenuated. Similar results were obtained in the case of single bolus i.v. adenosine. The present result indicates that the augmentation of the adenosine action by nicorandil appears to be mediated by activation of ATP-sensitive K+ channels, closely linked with stimulation on A2 receptors by adenosine.
Saito
K
K
Central Research Laboratories, Chugai Pharmaceutical Co, Ltd, Tokyo, Japan.
Sakai
K
K
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D019806:Cromakalim / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D015221:Potassium Channels / Q000819:agonists*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D013805:Theobromine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D015221:Potassium Channels; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; C048599:N(6)-cyclopentyladenosine; C024311:N-cyclopropyl adenosine-5'-carboxamide; C057837:3,7-dimethyl-1-propargylxanthine; D000241:Adenosine; D013805:Theobromine; D005905:Glyburide