The involvement of ATP‐sensitive potassium channels in β‐adrenoceptor‐mediated vasorelaxation in the rat isolated mesenteric arterial bed

Abstract

We have used the isolated buffer‐perfused superior mesenteric arterial bed of the rat to assess the involvement of ATP‐sensitive potassium (KAtp) channels in the vasorelaxant responses to β‐adrenoceptor agonists. The vasorelaxant potencies of the non‐selective β‐adrenoceptor agonist, isoprenaline, the β1 adrenoceptor agonist, dobutamine and the β2‐adrenoceptor agonist, terbutaline were all significantly (P>0.05) reduced (isoprenaline, ED50=265±31 pmol v. 1.05 ± 0.42 nmol; dobutamine, ED50=294± 67 pmol v. 497 ± 115 pmol; terbutaline, ED50= 157 ±26 nmol v. 452 ± 120 nmol) in the presence of the KATP‐channel blocker, glibenclamide. The presence of glibenclamide only weakly influenced the vasorelaxant properties of salbutamol, a β2‐adrenoceptor agonist, while those of verapamil, a β‐adrenoceptor‐independent vasorelaxant, were unaffected. In radioligand binding experiments, glibenclamide (1 nM‐100 μm) did not displace any specific [3H]‐dihydroalprenolol binding from rat β‐adrenoceptors. Therefore, glibenclamide does not bind to β‐adrenoceptors at the concentration used in the present investigation. Vasorelaxant responses to dibutyryl cyclic AMP, the cell permeable analogue of cyclic AMP, were also unaffected by glibenclamide, indicating that the coupling of β‐adrenoceptors to KATP‐channels occurs independently of the elevation of intracellular cyclic AMP. We have shown that a significant element of the vasorelaxant responses to both β1 and β2 adrenoceptor activation involves the opening of KATP‐channels. In conclusion, KATP‐channels may play a physiological role in β‐adrenoceptor‐mediated vasodilatation. 1995 British Pharmacological Society