Original Article: PDF OnlyInhibition by Glibenclamide of Negative Chronotropic and Inotropic Responses to Pinacidil, Acetylcholine, and Adenosine in the Isolated Dog HeartMurakami, Makoto; Furukawa, Yasuyuki; Karasawa, Yasuyuki; Ren, Lei-Ming; Takayama, Shin; Chiba, Shigetoshi Author Information Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan Journal of Cardiovascular Pharmacology: April 1992 - Volume 19 - Issue 4 - p 618-624 Free Abstract The blocking effects of glibenclamide on the chronotropic and inotropic responses to K+ channel openers pinacidil (ATP-sensitive) and acetylcholine (ACh) or adenosine (receptor-operated) were investigated in the isolated, blood-perfused canine atrium or ventricle. Glibenclamide (0.1–3 μmol) induced no significant cardiac effects. Cumulative administration of pinacidil (0.03–3 μmol) dose-dependently decreased sinus rate much less than the contractile force of the atrial and ventricular muscles. Glibenclamide similarly inhibited the negative chronotropic and inotropic responses to pinacidil in a dose-related manner. A high dose of glibenclamide (3 μmol) slightly but significantly attenuated the negative chronotropic and inotropic responses to ACh and adenosine but not to verapamil. These results demonstrate that glibenclamide inhibits the negative chronotropic and inotropic responses to the ATP-sensitive K+ channel opener pinacidil and the receptor-operated K+ channel openers ACh and adenosine but more selectively antagonizes the responses to pinacidil in the dog heart and suggest that in contrast to ACh and adenosine, an ATP-sensitive K+ channel opener has a greater effect on the ventricle than on the sinoatrial node. © Lippincott-Raven Publishers.