Evidence for endothelin-induced renal vasoconstriction independent of ET(A) receptor activation

Academic Article

Abstract

  • Experiments were designed to examine the role of endothelin (ET) receptors, specifically ET(A) 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 ET(A) 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 ET(A) receptors and that ET(A) receptor activation may play a role in maintaining arterial pressure and renal vascular resistance in normal anesthetized rats.
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    Author List

  • Pollock DM; Opgenorth TJ
  • Volume

  • 264
  • Issue

  • 1 33-1