Ebelactone B, an inhibitor of urinary carboxypeptidase Y-like kininase, prevents the development of deoxycorticosterone acetate-salt hypertension in rats.
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.
Majima
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Ikeda
Y
Y
Kuribayashi
Y
Y
Mizogami
S
S
Katori
M
M
Aoyagi
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000652:urine*; D043402:Cathepsin A; D003404:Creatinine / Q000652:urine; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007704:Kininogens / Q000097:blood / Q000172:deficiency; D007705:Kinins / Q000652:urine; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood / Q000172:deficiency; D012964:Sodium / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007704:Kininogens; D007705:Kinins; D007783:Lactones; D003900:Desoxycorticosterone; C030795:ebelactone B; D012964:Sodium; D003404:Creatinine; D002268:Carboxypeptidases; D043402:Cathepsin A; D012083:Renin; D011188:Potassium