Cardiac electrophysiologic effects of a new calcium antagonist, lacidipine.
Lacidipine is a new 1,4-dihydropyridine derivative with potent and long-lasting antihypertensive activity. We used intracellular microelectrodes to characterize the electrophysiologic properties of lacidipine on different cardiac preparations. Lacidipine (10(-8) -10(-6) M) dose-dependently decreased contractility of driven sheep Purkinje fibers. For concentrations less than or equal to 10(-7) M, this effect was associated with a selective decrease of the plateau height. Higher concentrations (3 X 10(-7) and 10(-6) M), however, affected action potential amplitude, overshoot, and maximum rate of depolarization. In the same range of concentrations, lacidipine did not affect normal automaticity of guinea-pig sinus node and sheep Purkinje fibers. Lacidipine (10(-6) M) consistently blocked barium-induced abnormal automaticity in Purkinje fibers and reduced the amplitude and Vmax of the slow action potentials induced by histamine (10(-5) M) in guinea pig papillary muscle depolarized by potassium (22 mM). The effect of lacidipine on the slow inward current (Isi) was studied in shortened Purkinje fibers under voltage-clamp conditions. Lacidipine (10(-7)-10(-6) M) reduced the Isi without affecting the I-V relationship. None of the effects of lacidipine was reversed by 2-h washout. The results indicate that lacidipine has calcium-antagonistic properties in cardiac tissues. Its cardiac effects occur at concentrations 100 times higher than those active in the vascular smooth muscle. The lack of recovery of the lacidipine effects suggests that its interaction with the calcium channel may occur at an inner site of the cell membrane.
Department of Pharmacology, University of Firenze, Italy.
E
E
Cerbai
P
P
DeBonfioli Cavalcabó
I
I
Masini
S
S
Visentin
A
A
Giotti
A
A
Mugelli
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D012756:Sheep
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine