PHYSIOLOGICAL-ROLE OF ET(A) RECEPTORS IN THE REGULATION OF RENAL HEMODYNAMICS IN NORMAL AND SALT-DEPLETED RATS

Exogenous endothelin (ET) promotes powerful vasoconstriction in system ic and renal microcirculation. However, the physiologic role of endoge nous ET on the moment-to-moment regulation of the circulation remains unclear. We investigated the effects of acute administration of FR1393 17, a nonpeptide inhibitor specific for the ET(A) receptor shown in pr eliminary experiments to reverse the established vasoconstrictor effec ts of exogenous ET. Renal and glomerular functional parameters were de termined in eight anesthetized adult male Munich-Wistar rats receiving a standard diet (0.5% Na) before and after bolus injection of FR13931 7, 10 mg/kg. To assess the physiologic role of ET in sodium depletion, eight rats received a low-salt (0.06% Na) diet for 2 weeks before acu te FR139317 treatment. Eight additional salt-restricted rats received a bolus injection of the angiotensin II inhibitor losartan, 10 mg/kg i .v., as a positive control. FR139317 exerted no detectable microcircul atory effect in rats receiving standard diet. In sodium-depleted rats, losartan lowered blood pressure by 12 mm Hg, raised heart rate by 20 beats/min, and decreased renal vascular resistance by 33%. By contrast , FR139317 had only slight hemodynamic effects, although it increased heart rate by 15 beats/min. These results suggest that ET does not par ticipate, at least via ET(A) receptors, in the regulation of renal and systemic microcirculation in the rat. However, it may be involved in the circulatory adaptations to chronic sodium depletion. A regulatory role for ET via ET(B) receptors is also possible.