Effects of Glibenclamide on Negative Cardiac Responses to Cholinerg and Purinergic Stimuli and Cromakalim in the Isolated Dog Heart.

Abstract

ABSTRACT-We investigated the effects of an ATP-sensitive K+ channel blocker, glibenclamide, on the negative chronotropic and inotropic responses to intracardiac parasympathetic nerve stimulation, acetyl choline (ACh, a muscarinic receptor agonist), ATP (a P2-purinergic receptor agonist), adenosine (a P1-purinergic receptor agonist) and cromakalim (a potassium channel opener) in the isolated, blood-perfused canine right atrium or left ventricle. A high dose of glibenclamide (3 ttmol) did not affect the negative chronotropic and inotropic responses to parasympathetic stimulation (frequencies of 1 30 Hz), although it slightly but significantly attenuated the negative cardiac responses to exogenous ACh (0.3 -10 nmol). Furthermore, adenosine (0.03 0.3 umol)-induced negative chronotropic and inotropic responses were significantly in hibited by glibenclamide (3 pmol), but ATP (0.01-1 pmol)-induced negative cardiac responses were not affected. A cumulative administration of cromakalim (0.01-1 pcmol) dose-dependently caused much greater decreases in the contractile force of atrial and ventricular muscles than in sinus rate. Glibenclamide (0.3 3 ,umol) similarly blocked the negative chronotropic and inotropic responses to cromakalim in a dose-depend ent manner. These results suggest that glibenclamide modifies the negative cardiac responses to parasym pathetic activation both in pre and postjunctional sites and the responses to adenosine but not to ATP at K+ channels in the dog heart, although the modifications are minor under physiological conditions.