The effects of diltiazem (CRD-401) on the membrane and mechanical properties of vascular smooth muscles of the rabbit

Abstract

1 The effects of diltiazem on electrical and mechanical properties of vascular smooth muscles of the rabbit were examined by various experimental procedures. 2 In the pulmonary artery, diltiazem (0.1 to 10 microgram/ml) did not modify the membrane potential (-56 mV), length constant of the tissue (1.47 mm) or rectifying properties of the membrane. Diltiazem (0.1 to 10 microgram/ml) did not modify the membrane potential of the mesenteric artery (-62.5 mV). 3 Diltiazem (1 to 10 microgram/ml) suppressed mechanical responses of pulmonary and mesenteric arteries induced either by direct stimulation of the muscle (1.0 s pulse) or by neural activation (0.5 ms pulse, 30 Hz and 10 s total duration). Diltiazem suppressed the contraction induced by nerve stimulation to a greater extent than that induced by direct muscle stimulation. 4 When the depolarization-contraction relationship of the smooth muscle of the pulmonary artery was observed by voltage clamp technique, diltiazem (1 to 10 microgram/ml) raised the critical membrane potential to evoke contraction from 5 mV to 12 mV, and reduced the amplitude of contraction obtained at any given depolarization level. 5 In the pulmonary artery, diltiazem (10 microgram/ml) suppressed K-induced contraction and raised the mechanical threshold, while K-induced depolarization was not suppressed. Diltiazem (1 to 10 microgram/ml) also suppressed noradrenaline-induced contraction, raised the mechanical threshold and suppressed noradrenaline-induced depolarization. 6 The vasodilator actions of diltiazem on the vascular smooth muscle were compared to vasodilator actions observed with other Ca-antagonists.