ENDOTHELIN ANTISERUM DECREASES VOLUME-STIMULATED AND BASAL PLASMA-CONCENTRATION OF ATRIAL-NATRIURETIC-PEPTIDE

Background. Endothelin-1 (ET-1) is the most powerful factor known to r elease atrial natriuretic peptide (ANP) in vivo and in cultured cardia c myocytes or preparations of atrium. We tested the role of endogenous ET-1 in the regulation of ANP release by passive immunization in anes thetized rats. Methods and Results. Intravenous injection of antiserum against ET-1 was shown to decrease basal and volume-stimulated plasma concentrations of ANP, whereas control serum was without effect. Anti serum generated in rabbits cross-reacted 100% with endothelin-2 and -3 . In pentobarbital-anesthetized Wistar rats treated with ET-1 antiseru m, plasma ANP concentration measured by radioimmunoassay was reduced b y 37% from starting level after 10 minutes and by 30% after 60 minutes . Control rat serum had no effect on plasma ANP. Rapid intravenous inf usion of 8 mL of 0.9% NaCl caused a sixfold increase of plasma ANP con centration in control rats but only twofold in rats pretreated with ET -1 antiserum (P<.01). This effect of ET-1 antiserum was dose dependent . ET-1 antiserum changed neither blood pressure nor heart rate signifi cantly in anesthetized rats. Pretreatment with ET-1 antiserum did not affect the initial hypotensive response to intravenous ET-1 0.5 nmol/k g but significantly attenuated the subsequent hypertensive response to endothelin. Conclusions. Endothelin may be a physiological modulator of both basal and stimulated ANP release.