Differential sensitivity to calcium entry blockade of angiotensin II-induced contractions of rat and guinea-pig aorta.
Angiotensin II-amide (A II) elicits a concentration-dependent contraction of vascular smooth muscle. This vasoconstriction proved sensitive to calcium entry blockade, more so in rat aorta than in guinea-pig aorta. The structurally different calcium entry blockers (CEB) nifedipine, verapamil and diltiazem, concentration-dependently impaired A II-induced vasoconstriction of rat aortic strips until almost complete suppression was obtained. The same pattern of inhibition could be demonstrated by lowering the calcium content of the bath fluid. In guinea-pig aortic preparations, however, complete suppression of the constrictor effect to A II could not be achieved. Diltiazem proved more effective in inhibiting the maximal vasoconstriction to A II than nifedipine and verapamil. For comparison, the ratio between the inhibitory potencies of the CEB studied on vasoconstriction elicited by A II and on K+-induced contractions in both species were calculated; this resulted in A II/K+ ratios close to unity for rat aorta. In guinea-pig aortic strips the ratios proved to vary with the CEB used. In this species, a difference in sensitivity of both influx processes was found both for nifedipine and diltiazem. These findings would implicate the existence of a receptor-operated channel, activated by A II and thus triggering vasoconstriction in addition to the potential-operated channel which can be activated by depolarization.
van Heiningen
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Division of Pharmacotherapy, Academic Medical Centre, University of Amsterdam, The Netherlands.
van Zwieten
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PA
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D013045:Species Specificity; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D000804:Angiotensin II; D014700:Verapamil; D004110:Diltiazem; D009638:Norepinephrine; D011224:Prazosin