Prostaglandin E2 abrogates endothelin-induced vasoconstriction in renal outer medullary descending vasa recta of the rat

Abstract

Endothelins (ET) and prostaglandin E2 are synthesized in the inner medulla by collecting duct epithelium and interstitial cells, respectively. All ascending vasa recta (AVR) blood returns from the inner medulla to the cortex in outer medulary vascular bundles. We reasoned that hormones might influence medullary blood flow by diffusing across AVR fenestrations to modulate vasoconstriction of outer medullary descending vasa recta (OMDVR). To investigate this possibility, OMDVR dissected from vascular bundles were exposed to ET-1, 2, or 3. Each endothelin isoform induced stable vasoconstriction with potency, ET-1 > ET-2 > ET-3 (EC50, 1.8 x 10-15, 5.9 x 10-12, and 8.8 x 10-10 M, respectively). The ET(A) receptor antagonists BQ-123 and BQ-610 (10-6 M), as well as an ET(A) and ET(B) receptor antagonist combination, attenuated vasoconstriction due to ET-1 (10-12 M). BQ-123 had no effect on the response to ET-3 (10-8 M). The ET(B) receptor antagonist BQ-788 (10-6 M) attenuated the response to ET-3 (10-10 M), but not that to ET-1 (10-12 M). Finally, PGE2 (10-6 M) reversibly dilated OMDVR preconstricted with ET-1 (10-12 M) or ET-3 (10-8 M) but not ET-1 (10-10 M) . We conclude that ET-1, 2, and 3 are potent constrictors of OMDVR and the response to ET-1 is mainly ET(A) receptor subtype mediated, while ET-3 acts via the ET(B). PGE2 modulates ET induced constriction. These findings are consistent with interactive feedback and control of medullary perfusion by locally synthesized hormones.