Verapamil and diazoxide antagonism of agonist-induced contractions of aortic strips from normal and spontaneously hypertensive rats (SHR).
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.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D003981:Diazoxide / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008729:Methoxamine / Q000037:antagonists & inhibitors; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D011458:Prostaglandins E / Q000037:antagonists & inhibitors; D051381:Rats; D014700:Verapamil / Q000494:pharmacology*
D011458:Prostaglandins E; D011189:Potassium Chloride; D014700:Verapamil; D008729:Methoxamine; D003981:Diazoxide