THE INVOLVEMENT OF ATP-SENSITIVE POTASSIUM CHANNELS IN BETA-ADRENOCEPTOR-MEDIATED VASORELAXATION IN THE RAT ISOLATED MESENTERIC ARTERIAL BED

1 We have used the isolated buffer-perfused superior mesenteric arteri al bed of the rat to assess the involvement of ATP-sensitive potassium (K-ATP) channels in the vasorelaxant responses to beta-adrenoceptor a gonists. 2 The vasorelaxant potencies of the non-selective beta-adreno ceptor agonist, isoprenaline, the beta(1)-adrenoceptor agonist, dobuta mine and the beta(2)-adrenoceptor agonist, terbutaline were all signif icantly (P<0.05) reduced (isoprenaline, ED(50)=265+/-31 pmol v. 1.05+/ -0.42 nmol; dobutamine, ED(50)=294+/- 67 pmol v. 497+/-115 pmol; terbu taline, ED(50)=157+/-26 nmol v. 452+/-120 nmol) in the presence of the K-ATP-channel blocker, glibenclamide. 3 The presence of glibenclamide only weakly influenced the vasorelaxant properties of salbutamol, a b eta(2)-adrenoceptor agonist, while those of verapamil, a beta-adrenoce ptor-independent vasorelaxant, were unaffected. 4 In radioligand bindi ng experiments, glibenclamide (1 nM-100 mu M) did not displace any spe cific [H-3]-dihydroalprenolol binding from rat beta-adrenoceptors. The refore, glibenclamide does not bind to beta-adrenoceptors at the conce ntration used in the present investigation. 5 Vasorelaxant responses t o dibutyryl cyclic AMP, the cell permeable analogue of cyclic AMP, wer e also unaffected by glibenclamide, indicating that the coupling of be ta-adrenoceptors to K-ATP-channels occurs independently of the elevati on of intracellular cyclic AMP. 6 We have shown that a significant ele ment of the vasorelaxant responses to both beta(1)- and beta(2)-adreno ceptor activation involves the opening of K-ATP-channels. In conclusio n, K-ATP-channels may play a physiological role in beta-adrenoceptor-m ediated vasodilatation.