Endothelin ETA and ETB receptors mediate vasoconstriction and prostanoid release in the isolated kidney of the rat.

ABSTRACT

Endothelin-1 or sarafotoxin 6c (10(-12) to 10(-9) M) induced concentration-dependent increases in perfusion pressure in the isolated perfused kidney of the rat, and increased the release of 6-keto-prostaglandin F1 alpha, prostaglandin E2 and prostaglandin F2 alpha. The pressor effects of endothelin-1 were partially antagonised by BQ-123 (10(-6) M) and more strongly so by the endothelin ETA/B receptor non-selective antagonist PD 145065 (10(-6) M). PD 145065, but not BQ-123, also completely blocked the pressor effects of sarafotoxin 6c. The releases of prostanoids induced by endothelin-1 were greatly reduced by infusion of either BQ-123 or PD 145065, whereas PD 145065, but not BQ-123, strongly antagonised the releases induced by sarafotoxin 6c. These results indicate that the vasoconstrictions and the prostanoid releases induced by the endothelin/sarafotoxin peptides are mediated by the activation of both endothelin ETA and endothelin ETB receptors in the isolated perfused kidney of the rat.