ETA receptors mediate vasoconstriction, whereas ETB receptors clear endothelin-1 in the splanchnic and renal circulation of healthy men

The contribution of the endothelin (ET) receptors ET(A) and ET(B) to basal vascular tone and ET-1-induced vasoconstriction in the renal and splanchnic vasculature was investigated in six healthy humans. ET-1 was infused alone and in combination with the selective ET(A) receptor antagonist BQ123 or the selective ET(B) receptor antagonist BQ788 on three different occasions. BQ123 did not affect basal arterial blood pressure, splanchnic vascular resistance (SplVR) or renal vascular resistance (RVR), but inhibited the increase in vascular resistance induced by ET-1 [64+/-18 versus -1+/-7% in SplVR ( P <0.05); 36+/-6 versus 12+/-3% in RVR ( P <0.0001)]. BQ788 increased basal SplVR and RVR [38+/-16% ( P =0.01) and 21+/-5% ( P <0.0001) respectively], and potentiated the ET-1-induced vasoconstriction. Plasma ET-1 increased more after ET(B) blockade than under control conditions or after ET(A) blockade. These findings suggest that the ET(A) receptor mediates the splanchnic and renal vasoconstriction induced by ET-1 in healthy humans. The ET(B) receptor seems to function as a clearance receptor and may modulate vascular tone by altering the plasma concentration of ET-1.