Endothelin-3 (ET-3), a recently described vasoconstricting peptide was infused in Inactin anesthetized rats at 0, 40, 170 or 340 ng/kg/min for 45 minutes (n = 8 in each group). ET-3 infusion increased mean arterial pressure at all infusion rates by increasing total peripheral resistance. Cardiac output (delta CO) was significantly decreased at the two highest ET-3 infusion doses. The decrease in cardiac output was associated with a decrease in central venous pressure and stroke volume and an increase in hematocrit. ET-3 infusion at 40 ng/kg/min increased sodium excretion (delta UNaV) by 0.14 +/- 0.08 microEq/min (p less than 0.05 compared to vehicle infusion) without affecting the glomerular filtration rate (GFR). At higher infusion rates ET-3 markedly decreased the GFR, urine flow and urinary potassium excretion. ET-3 infusion significantly increased circulating levels of ANF. The present study demonstrates that ET-3 increases blood pressure by increasing total peripheral resistance but decreases cardiac output. Further, ET-3 has natriuretic effects at low doses but markedly attenuates renal function at high doses.