Effects of glibenclamide on negative cardiac responses to cholinergic and purinergic stimuli and cromakalim in the isolated dog heart.
We investigated the effects of an ATP-sensitive K+ channel blocker, glibenclamide, on the negative chronotropic and inotropic responses to intracardiac parasympathetic nerve stimulation, acetylcholine (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 of left ventricle. A high dose of glibenclamide (3 mumol) 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 mumol)-induced negative chronotropic and inotropic responses were significantly inhibited by glibenclamide (3 mumol), but ATP (0.01-1 mumol)-induced negative cardiac responses were not affected. A cumulative administration of cromakalim (0.01-1 mumol) dose-dependently caused much greater decreases in the contractile force of atrial and ventricular muscles than in sinus rate. Glibenclamide (0.3-3 mumol) similarly blocked the negative chronotropic and inotropic responses to cromakalim in a dose-dependent manner. These results suggest that glibenclamide modifies the negative cardiac responses to parasympathetic 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.
Murakami
M
M
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Furukawa
Y
Y
Chiba
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D018679:Cholinergic Agonists; D019806:Cromakalim; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D058913:Purinergic Agonists; D011758:Pyrroles / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects; D011983:Receptors, Purinergic / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D018679:Cholinergic Agonists; D015221:Potassium Channels; D058913:Purinergic Agonists; D011758:Pyrroles; D011950:Receptors, Cholinergic; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D019806:Cromakalim; D000255:Adenosine Triphosphate; D000241:Adenosine; D000109:Acetylcholine; D005905:Glyburide