AJP - Renal Physiology, Vol 264, Issue 4 678-F683, Copyright © 1993 by American Physiological Society
Natriuretic peptides inhibit mesangial cell production of endothelin induced by arginine vasopressin
M. Kohno, T. Horio, M. Ikeda, K. Yokokawa, T. Fukui, K. Yasunari, K. Murakawa, N. Kurihara and T. Takeda
First Department of Internal Medicine, Osaka City University Medical School, Japan.
The present study examined the effects of atrial, brain, and C-type
natriuretic peptides (ANP, BNP, and CNP, respectively) on endothelin-1
(ET-1) secretion after stimulation with arginine vasopressin (AVP), using
cultured rat glomerular mesangial cells. AVP stimulated immunoreactive (ir)
ET-1 secretion in a concentration-dependent manner via a receptor-mediated
process. Rat ANP-(1-28) and rat BNP-45 potently inhibited this stimulated
secretion in a concentration-dependent manner. Inhibition by ANP and BNP of
AVP-stimulated ET-1 secretion was paralleled by an increase in the medium
level of guanosine 3',5'-cyclic monophosphate (cGMP). The addition of a
cGMP analogue, 8-bromo-cGMP, reduced the stimulated ET-1 secretion. CNP was
much less effective than rat ANP-(1-28) or rat BNP-45 with respect to
inhibiting irET-1 secretion and increasing cGMP levels. High-performance
liquid chromatography indicated that the major component of irET-1 in the
culture medium corresponds to ET-1-(1-21). These findings indicate that AVP
stimulates ET-1 secretion in cultured rat mesangial cells and that rat ANP
and BNP inhibit this stimulated secretion, probably through a
cGMP-dependent process.
