Opening of ATP-sensitive K+ channels responsible for adenosine A2 receptor-mediated vasodepression does not involve a pertussis toxin-sensitive G protein.

Whether the opening of ATP-sensitive K+ channels responsible for adenosine A2 receptor-mediated vasodepression involves a pertussis toxin (PTX)-sensitive G protein was investigated in pithed rats. Adenosine and levcromakalim were used as reference substances. The blood pressure of pithed rats was kept elevated with an i.v. infusion of methoxamine. 2-(1-Octynyl)-adenosine (YT-146; 0.1-10 micrograms/kg i.v.), a selective adenosine A2 receptor agonist, produced a dose-dependent and long-lasting decrease in mean blood pressure (MBP) scarcely affecting heart rate (HR). Levcromakalim (0.3-10 micrograms/kg per min i.v. for 20 min) produced a dose-dependent and slowly developing decrease in MBP. The vasodepressor effects of YT-146 and levcromakalim were antagonized by glibenclamide (20 mg/kg i.v.), a blocker of ATP-sensitive K+ channels; the ED50 values for YT-146 and levcromakalim both increased about 2.5-fold. In rats pretreated with PTX (10 micrograms/kg i.v.), in which vagally induced bradycardia was nearly abolished, the vasodepressor effects of YT-146 and levcromakalim were slightly enhanced. Adenosine (0.3-10 mg/kg per min i.v. for 1 min) produced a dose-dependent and long-lasting decrease in MBP accompanied by a transient decrease in HR. The vasodepressor effect of adenosine was antagonized by glibenclamide; the ED50 value for adenosine increased about 3.2-fold, but not after PTX pretreatment. In contrast, the transient bradycardia was antagonized by PTX pretreatment but not by glibenclamide. These results suggest that the opening of ATP-sensitive K+ channels in vascular smooth muscle following stimulation of adenosine A2 receptors by YT-146 and adenosine does not involve a PTX-sensitive G protein.(ABSTRACT TRUNCATED AT 250 WORDS)