Atrial natriuretic factor and endothelin interactions in control of vascular tone

Endothelin-1 (ET-1) is reported to be the most powerful constrictor of blood vessels known. Atrial natriuretic factor is a potent relaxor of contracted vessels. This study examined the potential interaction between these vasoactive peptides on rabbit aortic rings. ET-1 contracted the rings in a dose-dependent manner with an EC50 (-log M) of 9.78 +/- 0.16. Atriopeptin III (APIII) completely relaxed ET-1 (10(-9) M)-contracted rings with an EC50 of 9.63 +/- 0.07 and methoxamine contracted rings with an EC50 of 9.18 +/- 0.09. Pretreatment of aortic rings with APIII (up to 3 x 10(-6) M) did not alter the normal ET-1 dose-response curve with respect to potency but did diminish the maximal contraction achieved. An interesting additional finding was that the temporal nature of ET-1-induced contraction is remarkably dose-variable. In conclusion, the potent contractile effects of ET-1 on vascular smooth muscle can be effectively reversed but not prevented by APIII.