Inhibition of kinin degradation on the luminal side of renal tubules reduces high blood pressure in deoxycorticosterone acetate salt-treated rats

1. To determine whether the antihypertensive response in deoxycorticosteron e acetate (DOCA) salt-treated rats was mediated by kinins on the luminal si de of renal tubules or in the circulation, selective urinary kininase inhib itors were administered to normal Brown Norway Kitasato (BN-Ki) rats and ki ninogen-deficient Brown Norway Katholiek (BN-Ka) rats. 2. Kinins were degraded by neutral endopeptidase (NEP) and carboxypeptidase Y-like kininase (CPY) in urine, but were inactivated mainly by angiotensin -converting enzyme (ACE) in the plasma. 3. Ebelactone B inhibited CPY, while poststatin inhibited CPY and NEP. 4. Daily administration of poststatin (5 mg/kg per day, s.c.) for 3 days re duced blood pressure (BP) in DOCA salt-treated BN-KI rats, but not in BN-Ka rats. 5. Ebelactone B (5 mg/kg per day, s.c.) also reduced BP in BN-Ki rats, whic h was accompanied by increased urinary sodium excretion, but had no effect on BP in BN-Ka rats. 6. Lisinopril (5 mg/kg per day, s.c.) had no effect on BP in either rat str ain. 7. Arterial kinin levels in BN-Ki rats increased significantly (2.2-4.6 pg/ mL) with captopril (10 mg/kg, s.c.). However, arterial kinin levels that in duced hypotension following the infusion of bradykinin (1000 ng/kg per min, i.v.) were 110-fold higher than endogenous arterial kinin levels attained following captopril. 8. These results suggest that inhibition of kinin degradation on the lumina l side of the renal tubules may effectively attenuate hypertension.