The participation and interactions of the vasopressor (e.g., renin-angiotensin) and vasodepressor (e.g., prostaglandin and kallikrein-kinin) systems of the kidney will be assessed respectively for possible prohypertensive and antihypertensive mechanisms involved in both the one- and two-kidney models of unilateral renovascular hypertension. The proposed studies will be conducted in trained, unanesthetized dogs serving as their own controls. The effects of acute and subacute systemic administrations of a peptidyl-dipeptide hydrolase inhibitor (SQ20881 or angiotensin converting enzyme and kininase II inhibitor), an angiotensin II antagonist (saralasin), two prostaglandin synthetase inhibitors (indomethacin and meclofenamate) and a kallikrein inhibitor (aprotinin), given alone and in combination, will be studied in both models. The effects of intra-arterial infusions of these same pharmacological agents into the stenotic kidney of the one-kidney model and the non-stenotic kidney of the two-kidney model will also be studied, in order to differentiate their systemic and intrarenal effects on arterial pressure, electrolyte and fluid balance, urinary kinin and prostaglandin-E2 excretions, plasma renin activity and reactivity of peripheral and renal venous blood, and plasma aldosterone concentrations, as well as effects on systemic vascular reactivity to angiotensin II. In addition, renal venous plasma will be bioassayed for the detection of non-renin pressor activity and pressor-potentiating activity in both models.