We have previously reported that the renal kallikrein-kinin system suppressed the development of
hypertension, using
kininogen deficient Brown Norway Katholiek rats.
Kinins were degraded in urine mainly by
carboxypeptidase Y-like kininase (CPY). Blockade of renal
kinin degradation may prevent the experimental
hypertension through the facilitation of the renal kallikrein-kinin system. Daily administration of
ebelactone B (EB), which is isolated from Actinomycetes and strongly inhibits CPY, from the first day of
deoxycorticosterone acetate (
DOCA)-
salt treatment for 4 weeks completely blocked
hypertension in Sprague-Dawley rats. This treatment reduced
sodium levels in erythrocytes and cerebrospinal fluids (CSF) significantly. By contrast, an
ACE inhibitor,
lisinopril did not prevent
hypertension. The development of
hypertension in young spontaneously hypertensive rats was also blunted by EB with reductions in
sodium levels in erythrocytes and in CSF. The arterial
kinin levels in rats undergoing
DOCA-
salt treatment were 2.2 +/- 0.2 pg/ml, which were increased significantly to 4.6 +/- 0.4 pg/ml with
captopril (10 mg/kg, s.c.). The increased
kinin levels were less than those to show
hypotension. EB did not increase the arterial
kinin levels, with significant increase in urinary
kinin secretion. These results suggested that facilitation of the renal kallikrein-kinin system by inhibition of
kinin degradation on the
luminal side of the renal tubules may effectively prevent
hypertension.