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

https://doi.org/10.1016/0014-2999(95)00320-KGet rights and content

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.

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      2010, Tetrahedron
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      The ebelactones display a wide range of biological activity consequent to the irreversible acylation of various serine hydrolases by the strained β-lactone moiety.3,4 Examples together with their protein targets include suppressed fat absorption (intestinal lipase),5 suppression of platelet aggregation (cathepsin A/deamidase),6 antihypertension (urinary kininase)7,8 and immunostimulation (N-formylmethionine aminopeptidase).1 In addition, the ebelactones inhibit cutinases produced by fungal plant pathogens thereby blocking the initial step of plant infection,9,10 and they reduce the destruction of human epidermal and epithelial tissue by pathogenic yeast.11

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