Ebelactone B, an inhibitor of urinary carboxypeptidase Y-like kininase, prevents the development of deoxycorticosterone acetate-salt hypertension in rats

Abstract

Kininogen-deficient Brown Norway Katholiek rats (BN-Ka) excrete little urinary kinin, compared with normal rats of the same strain (BN Kitasato rats (BN-Ki)). Deoxycorticosterone acetate-salt treatment increased systolic blood pressure in both rats, but much faster in BN-Ka than in BN-Ki. Daily subcutaneous administration of ebelactone B (15 and 5 mg/kg/day), a rat urinary carboxypeptidase Y-like kininase inhibitor, significantly reduced systolic blood pressure in BN-Ki, but not in BN-Ka. This treatment significantly increased urinary Na + excretion and reduced Na + concentration in the erythrocytes in BN-Ki, but not in BN-Ka. An angiotensin-converting enzyme inhibitor, lisinopril (5 mg/kg/day s.c.), did not reduce the systolic blood pressure in either BN-Ki or BN-Ka. These results suggested that ebelactone B has promise as a preventive agent for the development of hypertension acting through the inhibition of urinary kinin degradation.