Our major objective is to help clarify the roles of metabolic enzymes (""""""""converting"""""""" and inactivating enzymes) in limiting or modulating the physiologic and pathologic actions of kinins and agniotensins. The objective will be approached in three general ways. 1. Using angiotensins or kinins labelled intrinsically with 3H at high specific radioactivity (e.g. [3H]Phe5-bradykinin or [3H]Phe8-angiotensin I; either at 25 ci/mmole), we will examine for the occurrence of inactivating and converting enzymes in addition to angiotensin converting enzyme (ACE; kininase II). Beacuse the lungs are the last organ traversed before venous blood becomes arterial blood, we will use isolated, perfused lungs and pulmonary endothelial cells in culture. 2. We will examine the metabolic fate and structure-activity relationships of BPP9a, a highly effective inhibitor of ACE. We believe that BPP9a provides a template for the designing of ACE inhibitors more effective than those available at present. 3. We will continue to purify and haracterize naturally-occurring inhibitors of ACE and will add a study of naturally-occurring inhibitors of renal:urinary kallikrein. We have shown that the ACE inhibitors vary with diet, and the possibility is suggested that variations of their concentrations may be important to blood pressure homeostasis. Success in our studies overall should improve understanding of how kinin and angiotensin """"""""converting"""""""" and inactivating enzymes participate inthe regulation of the renin-angiotensin and kallikrein-kinin systems.
| Ryan, J W (1988) Arginine carboxypeptidase and its inhibitors. Methods Enzymol 163:186-94 |
| Ryan, J W (1988) Angiotensin-converting enzyme, dipeptidyl carboxypeptidase I, and its inhibitors. Methods Enzymol 163:194-210 |
| Chung, A Y; Ryan, J W; Ryan, J P et al. (1986) Radiolabelled substrates for angiotensin converting enzyme. Adv Exp Med Biol 198 Pt A:427-33 |
| Ryan, J W; Chung, A Y; Berryer, P et al. (1986) Slow tight binding inhibitors of angiotensin converting enzyme. Adv Exp Med Biol 198 Pt A:419-25 |
| Ryan, J W; Berryer, P; Hart, M A et al. (1986) Aggregate anaphylaxis and carboxypeptidase N. Adv Exp Med Biol 198 Pt A:435-43 |
| Ryan, U S; Ryan, J W; Crutchley, D J (1985) The pulmonary endothelial surface. Fed Proc 44:2603-9 |
