Md. Randall et Ai. Mcculloch, THE INVOLVEMENT OF ATP-SENSITIVE POTASSIUM CHANNELS IN BETA-ADRENOCEPTOR-MEDIATED VASORELAXATION IN THE RAT ISOLATED MESENTERIC ARTERIAL BED, British Journal of Pharmacology, 115(4), 1995, pp. 607-612
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.