Influence of pH changes on the actions of verapamil on cardiac excitation-contraction coupling.
Langendorff preparations of Sprague-Dawley rat hearts were perfused with calcium-free Krebs solution of pH 7.48 (control), 7.26 (acidosis) or 7.69 (alkalosis) containing either adrenaline or potassium. The responses of the force of contraction, coronary perfusion pressure and heart rate to graded doses of calcium preceded by a single dose of verapamil were measured. Contractile responsiveness to calcium was reduced during acidosis in both adrenaline- and potassium-stimulated hearts but was increased or reduced during alkalosis with adrenaline- or potassium stimulation, respectively. The efficacy of verapamil as a calcium antagonist increased during acidosis or alkalosis in both adrenaline- and potassium-stimulated hearts. In conclusion, acidosis or alkalosis inhibits potassium-stimulated contractions of the heart and enhances the effects of verapamil on potassium- and adrenaline-mediated contractions. Acidosis inhibits and alkalosis enhances adrenaline-stimulated contractions.
Achike
F I
FI
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
Dai
S
S
D000138:Acidosis / Q000503:physiopathology; D000471:Alkalosis / Q000503:physiopathology; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology*
D015220:Calcium Channels; D014700:Verapamil; D011188:Potassium; D002118:Calcium; D004837:Epinephrine