The major objectives are to determine the mechanisms by which the angiotensins and kinins are formed, exert their actions and are inactivated during passage through the lungs and two of their major target organs: the adrenal glands and kidneys. Formation of angiotensins II and III will be studied using synthetic angiotensin I and des-Asp 1-angiotensin I labelled intrinsically with tritium. Chemical identification of metabolites will be supplemented by biological and radioimmunoassays. The formation of bradykinin can be detected similarly, e.g. using labelled kallidin and Met-kallidin. The labelled kinins and angiotensins will be prepared by synthesis of analogs (e.g. containing (I) Phe and/or delta 3-Pro residues) suitable for $ catalytic tritiation. The actions of the angiotensins and kinins will be studied by examining the effects of these polypeptides on vascular smooth muscle and on specific secretory activities of the adrenal gland. Secretory activities will be monitored by biochemical and morphological methods. The latter studies will be supplemented by examining interrelationships of solution structure and biological activities. Specific metabolic steps leading to the inactivation of bradykinin and angiotensins II and III will be studied using intrinsically labelled hormones in organ perfusion. The subcellular localization of converting enzyme will be examined by immunocytochemical techniques. BIBLIOGRAPHIC REFERENCES: Ryan, J.W., Ryan U.S., Schultz, D.R., Day, A.R. and Dorer, F.E.: Further evidence on the subcellular sites of kininase II (angiotensin coverting enzyme). Adv. Exp. Med. Biol. 70:235-243, 1976. Ryan, U.S., Ryan J.W. and Chiu, A.T.: Kininase II (angiotensin coverting enzyme) and endothelial cells in culture. Adv. Exp. Med. Biol. 70:217-227, 1976.