EVIDENCE FOR ENDOTHELIN-INDUCED RENAL VASOCONSTRICTION INDEPENDENT OF ETA RECEPTOR ACTIVATION

Experiments were designed to examine the role of endothelin (ET) receptors, specifically ETA receptors, in mediating the renal vasoconstrictor effects of ET-1 in anesthetized Sprague-Dawley rats. Intravenous infusion of ET-1 at 25 pmol.kg-1.min-1 for 60 min produced a significant increase in mean arterial pressure (20 +/-7%) and decreases in renal plasma flow (-60 +/- 6%) and glomerular filtration rate (-47 +/- 6%). Renal vascular resistance was significantly increased from 17 +/- 1 mmHg.ml-1.min.g kidney wt during control period to 54 +/- 11 mmHg.ml-1.min.g kidney wt during the experimental period. A second group of rats was infused with both ET-1 and the specific ETA receptor antagonist BQ-123 (0.1 mg.kg-1.min-1). ET-1-induced increases in mean arterial pressure were completely blocked by BQ-123 (the average change was -7 +/- 4%). However, the renal vasoconstrictor effects of ET-1 were not affected by the antagonist, since renal plasma flow and glomerular filtration rate were again significantly reduced (-54 +/- 4 and -56 +/- 6%, respectively). Once again, renal vascular resistance was significantly increased from 16 +/- 2 mmHg.ml-1.min-g kidney wt during the control period to 33 +/- 5 mmHg.ml-1.min.g kidney wt during the experimental period. In a third group, infusion of BQ-123 alone produced a significant decline in mean arterial pressure (-13 +/- 2%), with no significant changes in renal plasma flow or glomerular filtration rate, thus producing a significant decrease in renal vascular resistance (15 +/- 1 vs. 11 +/- 2 mmHg.ml-1.min.g kidney wt). These results suggest that ET-induced renal vasoconstriction is not mediated by ETA receptors and that ETA receptor activation may play a role in maintaining arterial pressure and renal vascular resistance in normal anesthetized rats.