Verapamil and diazoxide antagonism of agonist-induced contractions of aortic strips from normal and spontaneously hypertensive rats (SHR)

Abstract

The vulnerability of aortic strips from 50-52 week old Spontaneously Hypertensive Rats (SHR) and normotensive Wistar-Kyoto (WKY) controls to the inhibitory or relaxing effects of the calcium antagonists verapamil and diazoxide was studied. Verapamil produced concentration-dependent inhibition (antagonism) of KCl, PGE2, and methoxamine-induced contraction of aortic strips from SHR and WKY. KCl and PGE2-induced contraction of SHR tissue were less readily antagonized by verapamil compared to WKY preparations. The reverse was seen with methoxamine-induced contraction. The slope of the verapamil inhibition curve of KCl-induced contraction was significantly steeper for aortic strips form WKY. Verapamil and diazoxide also produced concentration-dependent relaxation of KCl-induced contraction of aortic strips, no significant differences being noted in SHR and WKY responses. Results are compatible with the hypothesis that arterial smooth muscle from SHR is characterized by a more tightly bound pool or source of activator Ca++ which is released by certain agonists. Failure to observe a significant difference in verapamil or diazoxide induced relaxation of KCl contracted tissues from SHR or WKY suggests that in the tonic phase of KCl contraction, transmembrane fluxes of Ca++ in SHR and WKY are equally vulnerable to the Ca++ channel inhibitory effect of the antagonists.