Renal effects of endothelin (ET)-3 have been described in normotensive but not spontaneously hypertensive rats (SHR). Infusion (170 ng/kg/min) of the ETB receptor selective agonists ET-3 and sarafotoxin S6c (SS6c) was used to investigate ETB receptor modulation of renal function in SHR. ET-3 decreased glomerular filtration rate (GFR) and renal plasma flow (RPF) by approximately 95% (0.1 +/- 0.01 and 0.1 +/- 0.02 ml/min, respectively) versus vehicle (1.3 +/- 0.08 and 3.6 +/- 0.23, respectively) in SHR. ET-3 exerted a biphasic effect on urine flow (UV); an initial increase and then a decrease (vehicle, 4.2 +/- 0.55; ET-3, 0.2 +/- 0.09 microliter/min). ET-3 increased mean arterial pressure (vehicle, 159 +/- 4.1; ET-3, 174 +/- 3.1 mm Hg). SS6c decreased GFR and RPF by approximately 60% (0.8 +/- 0.12 and 2.0 +/- 0.18 ml/min, respectively) versus vehicle (2.0 +/- 0.19 and 5.2 +/- 0.45, respectively). UV did not change. Depressor effects of SS6c were observed (vehicle, 154 +/- 1.5; SS6c, 127 +/- 3.1 mm Hg). The ETB receptor selective agonists ET-3 and SS6c markedly decreased GFR and RPF in SHR, suggesting that endogenous ET-3 may modulate renal function through ETB receptors in SHR.