The goal of this project is to understand and control the effects of peptide hormones, such as bradykinin and angiotensin, on the circulatory system. Certain serious pathological states are characterized by excess production of these peptides. Previous work on this project has demonstrated that it is possible to make irreversibly acting inhibitors of the actions of these hormones or irreversible inhibitors of enzymes which metabolize them (both formation and destruction). These inhibitors are fragments or analogs of the hormones containing groups which will react with receptors or enzymes to form covalent bonds and link the peptide irreversibly to the receptor or enzyme. Such alkylating derivatives of the hormones should furnish useful drugs for control of the production, destruction, biological effects of endogenously produced hormones. Thus hypertension due to excess production of angiotensin could be controlled either by inhibition of enzymes which produce angiotensin or by blockage of angiotensin receptors. Long-acting hypotensive drugs could also result from irreversible inhibitors of enzymes which destroy bradykinin and other kinins.