Interactions between endothelin and atrial natriuretic factor in the rat aortic ring preparation

The potential interaction (s) between atrial natriuretic factor (ANF) and porcine–human endothelin (ET-1) was investigated in the endothelium-denuded rat aortic ring preparation. ET-1 produced a sustained contraction of aortic rings with an ED50 of 3.6 ± 0.49 × 10−9 M. Within the concentration range of 10−9 to 10−7 M, both rat ANF 103–126 and rat ANF 99–126 when preincubated with tissues reduced the contractile efficacy of ET-1 especially at low concentrations resulting in a small but significant rightward shift of the dose–response curve to ET-1. In contrast, at a concentration of 10−10 M, rANF 99–126 but not rANF 103–126 produced a significant leftward shift of the dose–response curve to ET-1 and an increase in the maximal developed tension for the dose–response curve to ET-1. For tissues incubated in the absence of extracellular calcium or in the presence of the calcium channel blocker nifedipine (5 × 10−7 M), both ANF derivatives produced a dose-dependent decrease in the maximum contraction, but no change in potency to ET-1. Addition of either rANF 103–126 or rANF 99–126 to tissues maximally contracted with ET-1 resulted in relaxation, reaching a maximum of 70%. The ED50 values for relaxation were 2.7 ± 0.51 × 10−8 and 3.5 ± 0.60 ± 10−8 M for rANF 103–126 and rANF 99–126, respectively. ET-1 did not interact with biologically responsive and clearance receptors for ANF. These results suggest that the major circulating form of ANF may act as a physiologic antagonist of endogenous ET-1 primarily affecting the intracellular calcium-dependent component of contraction to ET-1.Key words: endothelin, atrial natriuretic factor, rat aortic ring, contraction, relaxation.