Negative inotropic effect of pinacidil on the rat left atria.
Cromakalim at 50 microM and pinacidil at 0.1-10 microM had no effect, but pinacidil at 0.1 mM had a negative inotropic effect on the rat electrically-driven left atria without altering the positive inotropic responses to isoprenaline or phenylephrine alone. Glibenclamide had no effect but 4-aminopyridine, procaine (30 microM) and tetraethylammonium (3 mM) augmented the cardiac stimulation response. The ability of pinacidil to attenuate the cardiac stimulation response was not altered by glibenclamide, 4-aminopyridine or procaine but was prevented by pretreatment with tetraethylammonium. Thus, on the rat left atria, pinacidil has a negative inotropic effect which is unrelated to the opening of ATP-sensitive potassium channels, but may be due to opening the inward rectifying potassium channels.
Doggrell
S A
SA
Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D003864:Depression, Chemical; D004558:Electric Stimulation; D006146:Guanidines / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D020110:Pinacidil