CARDIOVASCULAR AND RENAL EFFECTS OF ENDOTHELIN-B RECEPTOR-SELECTIVE AGONISTS IN SPONTANEOUSLY HYPERTENSIVE RATS

Renal effects of endothelin (ET)-3 have been described in normotensive but not spontaneously hypertensive rats (SHR), Infusion (170 ng/kg/mi n) of the ET(B) receptor selective agonists ET-3 and sarafotoxin S6c ( SS6c) was used to investigate ET(B) receptor modulation of renal funct ion in SHR. ET-3 decreased glomerular filtration rate (GFR) and renal plasma flow (RPF) by similar to 95% (0.1 +/- 0.01 and 0.1 +/- 0.02 ml/ min, respectively) versus vehicle (1.3 +/- 0.08 and 3.6 +/- 0.23, resp ectively) in SHR. ET-3 exerted a biphasic effect on urine flow (UV); a n initial increase and then a decrease (vehicle, 4.2 +/- 0.55; ET-3, 0 .2 +/- 0.09 mu l/min). ET-3 increased mean arterial pressure (vehicle, 159 +/- 4.1; ET-3, 174 +/- 3.1 mm Hg). SS6c decreased GFR and RPF by similar to 60% (0.8 +/- 0.12 and 2.0 +/- 0.18 ml/min, respectively) ve rsus 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 ET(B) receptor selective agonists ET-3 and SS6c markedly decreased GFR and RPF in SHR, suggesting that endog enous ET-3 may modulate renal function through ET(B) receptors in SHR.