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/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.
Bird
J E
JE
Department of Pharmacology, Bristol-Meyers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA.
Giancarli
M R
MR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019334:Endothelin-3 / Q000494:pharmacology*; D005919:Glomerular Filtration Rate; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists*; D012039:Regional Blood Flow; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014757:Viper Venoms / Q000494:pharmacology*
D019334:Endothelin-3; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6