Role of cyclic GMP in the modulation by endothelium of the adrenolytic action of prazosin in the rat isolated aorta.

Taking their lead from studies which have shown that endothelium-derived relaxing factor(s) (EDRF) mediates vasorelaxation by activating smooth muscle guanyl cyclase, the authors of the current article have examined the role of the endothelium in relation to the effects of the alpha-adrenoceptor antagonist prazosin. Prazosin acted as a non-competitive antagonist of norepinephrine- (NE-) induced contraction in rat aortic preparations with intact endothelium, but as a competitive antagonist in endothelium-denuded preparations. The affinity of NE for its smooth muscle receptor was the same in the presence or absence of endothelium, but its efficacy was 7 times lower in the presence than in the absence of endothelium. Other experiments showed that inhibition of guanyl cyclase by methylene blue in the presence of endothelium (like endothelium removal) led to competitive antagonism of NE responses by prazosin, and that increasing the tissue content of cyclic GMP by pre-incubating de-endothelialized preparations with 8-Br-cyclic GMP (as in intact preparations) led to non-competitive antagonism of NE responses by prazosin. The authors concluded that EDRF, by increasing the cyclic GMP content of vascular smooth muscle of rat aorta, can modify the efficacy of NE, and thereby alter the mode of antagonism of prazosin.