Pathways of bradykinin degradation in blood and plasma of normotensive andhypertensive rats

Kinins are vasoactive peptide hormones that can confer protection against t he development of hypertension. Because their efficacy is greatly influence d by the rate of enzymatic degradation, the activities of various kininases in plasma and blood of spontaneously hypertensive rats (SHR) were compared with those in normotensive Wistar-Kyoto rats (WKY) to identify pathogenic alterations. Either plasma or whole blood was incubated with bradykinin (10 muM). Bradykinin and kinin metabolites were measured by high-performance l iquid chromatography. Kininase activities were determined by cumulative inh ibition of angiotensin I-converting enzyme (ACE), carboxypeptidase N (CPN), and aminopeptidase P (APP), using selective inhibitors. Plasma of WKY rats degraded bradykinin at a rate of 13.3 +/- 0.94 mu mol . min(-1) . l(-1). T he enzymes ACE, APP, and CPN represented 92% of this kininase activity, wit h relative contributions of 52, 25, and 16%, respectively. Inclusion of blo od cells at physiological concentrations did not extend the activities of t hese plasma kininases further. No differences of kinin degradation were fou nd between WKY and SHR. The identical conditions of kinin degradation in WK Y and SHR suggest no pathogenic role of kininases in the SHR model of genet ic hypertension.