Intracellular action of renin, angiotensin production and release.

The enzyme renin has been purified and characterized by structural analysis. Pure renin protein was used to produce a specific antibody to renin, which was useful in demonstrating the presence of a specific renin in many tissues other than kidney. In these cells angiotensins I and II and angiotensin converting enzyme were found to coexist with renin by immunohistochemical studies and by the direct determination with cultured cells. Studies with these cells indicated the local production of renin, angiotensinogen and angiotensins in these cells. Angiotensin II produced in the cultured cells was secreted to the outside of the cells while more than 95% renin remained within the cells. Secretion of angiotensin II from the angiotensin producing cells was demonstrated with perfused mesenteric artery. The secretion was stimulated by the adrenergic beta-agonist isoproterenol in a dose-dependent manner and specifically inhibited by a beta 2-antagonist. Angiotensin II secreted from the vascular bed by the beta 2-adrenoceptor stimulation acts locally to facilitate norepinephrine release. These studies demonstrate local production and secretion of angiotensin II and define its physiological role.