Experiments outlined in this grant proposal were designed to yield quantitative data whereby information concerning the relative importance of the renin-angiotensin system in the daily regulation of blood pressure could be obtained. The research differs from that generally being conducted on renin-angiotensin in other laboratories in that it is specifically aimed at gathering quantitative information to determine the role of this system as a blood pressure control mechanism. The specific areas of basic animal experimentation were designed to provide information to evaluate both the acute and chronic feedback gain of the system. The initial studies in the overall project have quantitated the acute feedback gain of the system and a number of the important intermediary relationships in the feedback loop. The results of these quantitative studies were then tested under various conditions such as hemorrhagic hypotension in dogs in order to gain a better understanding of the role that this system plays not only in the daily regulation of arterial pressure but also in situations of severe stress to the circulatory system. The chronic long-term effects of the system have been another important area of investigation. A number of projects have been designed to measure the long-term feedback gain of the system and are presently being conducted, including the actions of prolonged systemic and intrarenal infusions of angiotensin, Goldblatt hypertension, and the interaction of the renin-angiotensin system with the baroreceptor reflex system. Special characteristics of the system, such as sensitivity changes, are also being studied since these phenomena can provide valuable information concerning the possible role of the system in the genesis of hypertension. The quantitative data obtained from these experiments is being analyzed with the aid of mathematical computer modeling, which has proven to be a useful tool in predicting both normal and abnormal function as well as for the development of new experimental protocols.