ETA receptor‐mediated responses to endothelin‐1 and big endothelin‐1 in the rat kidney

Academic Article

Abstract

  • Renal clearance experiments were conducted in anaesthetized Sprague‐Dawley rats to determine the effect of the ETA receptor antagonist, BQ‐123, on the renal haemodynamic response to endothelin‐1 (ET‐1) and its precursor, big endothelin‐1 (big ET‐1) at doses that produce an equivalent degree of renal vasoconstriction. Infusion of either big ET‐1 at 100 pmol kg−1 min−1 or ET‐1 at 12 pmol kg−1 min−1 for 60 min produced almost identical decreases in renal blood flow (RBF) and glomerular filtration rate (GFR). Big ET‐1 produced an increase in mean arterial pressure (MAP) that was significantly larger than the increase produced by ET‐1. Co‐infusion with BQ‐123 (0.1 mg kg−1 min−1) prevented the rise in MAP produced by big ET‐1 and completely blocked the renal response. Similarly, BQ‐123 inhibited both the increase in MAP and the decrease in RPF and GFR produced by ET‐1. Big ET‐1 but not ET‐1, produced a significant increase in water and sodium excretion. BQ‐123 had no effect on the diuretic and natriuretic response to big ET‐1 consistent with possible ETB‐mediated inhibition of tubular reabsorption. We have previously shown that at higher doses of ET‐1, BQ‐123 was unable to inhibit the renal vasoconstrictor response despite blockade of the pressor response. Taken together, these results indicate that ET‐1 activates primarily ETA receptors at moderately low doses to produce renal vasoconstriction while higher doses also involve non‐ETA receptors. Since ET‐1 has a similar binding affinity for both ETA and ETB receptors, we suggest that there may be a third type of ET‐1 receptor in the rat kidney with lower affinity for ET‐1 that is coupled to a vasoconstrictor mechanism. 1994 British Pharmacological Society
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Pollock DM; Opgenorth TJ
  • Start Page

  • 729
  • End Page

  • 732
  • Volume

  • 111
  • Issue

  • 3