NATRIURETIC PEPTIDES INHIBIT MESANGIAL CELL PRODUCTION OF ENDOTHELIN-INDUCED BY ARGININE-VASOPRESSIN

The present study examined the effects of atrial, brain, and C-type na triuretic peptides (ANP, BNP, and CNP, respectively) on endothelin-1 ( ET-1) secretion after stimulation with arginine vasopressin (AVP), usi ng cultured rat glomerular mesangial cells. AVP stimulated immunoreact ive (ir) ET-1 secretion in a concentration-dependent manner via a rece ptor-mediated process. Rat ANP-(1-28) and rat BNP-45 potently inhibite d this stimulated secretion in a concentration-dependent manner. Inhib ition by ANP and BNP of AVP-stimulated ET-1 secretion was paralleled b y an increase in the medium level of guanosine 3',5'-cyclic monophosph ate (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 in creasing 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 secre tion in cultured rat mesangial cells and that rat ANP and BNP inhibit this stimulated secretion, probably through a cGMP-dependent process.