Effects of trapidil on electrical activities of canine ventricular muscle.
The effects of N,N-diethyl-5-methyl[1,2,4]triazolo[1,5-alpha]pyrimidine-7-amine (trapidil) on the electrical activities of canine right ventricular muscle were studied using standard microelectrode techniques. Trapidil (10(-4) and 10(-3) mol/l) increased the plateau amplitude and shortened the duration of the action potential without changing the resting membrane potential and the maximum rate of rise of the action potential. Trapidil (10(-3) mol/l) restored regenerative action potentials (the slow response) in the ventricular muscle depolarized by elevation of extracellular K+ concentrations to 30 mmol/l. The slow response induced by trapidil was not affected by pindolol (10(-7) mol/l) which abolished that elicited by isoprenaline (10(-6) mol/l). These results indicate that the action of trapidil on the cardiac cell membrane is to increase the slow inward current during the action potential independently of stimulation of beta-adrenoceptors. Taken together with the results obtained by previous investigations the present results suggest that the increase in slow inward current during the action potential would be responsible for the positive inotropic effect of trapidil and would probably be related to its inhibitory action on cyclic AMP phosphodiesterase.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology; D010869:Pindolol / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D014192:Trapidil / Q000494:pharmacology*
D011743:Pyrimidines; D010869:Pindolol; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D014192:Trapidil; D007545:Isoproterenol