Effect of nephrectomy and of adrenergic receptor blockers on the cardiorenal actions of endothelin.
The cardiorenal actions of endothelin-1 (ET-1) were evaluated in rats following nephrectomy, in rats during alpha-adrenergic blockade with phentolamine, and in rats during beta-adrenergic blockade with propranolol. Female rats were anesthetized with pentobarbital and, following surgery, were allowed 60 min to stabilize before 3 x 20 min-control clearances were collected. ET-1 was then infused at a rate of 100 ng kg-1 min-1 for 30 min, the infusion was stopped, and three additional clearances were collected. Four groups of rats were studied: in Group 1 (n = 10), ET-1 was infused; in Group 2 (n = 5), a bilateral nephrectomy was performed 120 min before infusing ET-1; in Group 3 (n = 5), ET-1 was infused into rats treated with phentolamine (0.015 mg kg-1 min-1); and in Group 4 (n = 5), ET-1 was infused into rats treated with propranolol (0.015 mg kg-1 min-1). At 30 min during infusion of ET-1 into Group 1 rats, mean arterial blood pressure had increased (P less than 0.01) by 27 +/- 2% (SE) and the glomerular filtration rate had decreased (P less than 0.01) by 71 +/- 6% of baseline values. Nephrectomy potentiated and prolonged the ET-1-induced systemic vasoconstriction. Phentolamine had no effect on the cardiorenal actions of ET-1 whereas propranolol enhanced ET-1-induced changes in mean arterial blood pressure; mean arterial blood pressure increased 38 +/- 2% at 30 min during ET-1 + propranolol infusion (P less than 0.01 versus value with ET-1 alone). These data indicate that the kidney affects ET-1-induced systemic vasoconstriction and that beta-adrenergic (but not alpha-adrenergic) receptors are activated during infusion of ET-1 with a resultant attenuation of ET-1-induced changes in systemic blood pressure.
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Department of Physiology and Biophysics, University of Cincinnati College of Medicine, Ohio.
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016232:Endothelins; D004730:Endothelium, Vascular; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D009392:Nephrectomy; D010455:Peptides / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D010455:Peptides; D012964:Sodium; D011433:Propranolol; D011188:Potassium; D010646:Phentolamine