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.
Opgenorth
T J
TJ
Abbott Laboratories, Abbott Park, IL 60064.
Novosad
E I
EI
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010446:Peptide Fragments; D011817:Rabbits
D016232:Endothelins; D010446:Peptide Fragments; C062525:atrial natriuretic factor prohormone (103-126); D009320:Atrial Natriuretic Factor; D008729:Methoxamine