ET-3 IS EXTRACTED BY AND INDUCES POTENT VASOCONSTRICTION IN HUMAN SPLANCHNIC AND RENAL VASCULATURES

To investigate splanchnic and renal vascular effects and elimination o f endothelin-3 (ET-3), ET-3 (10 pmol . kg(-1) . min(-1) iv for 20 min) was given to six healthy male volunteers. Arterial plasma ET-3-like i mmunoreactivity (ET-S-Li) increased 10-fold to 111 +/- 31 pmol/l (P < 0.01). The initial half-life of plasma ET-3-Li determined in three sub jects was 1.7 +/- 0.2 min. The fractional extraction of ET-3-Li was 68 +/- 7% in the splanchnic and 63 +/- 4% in the renal vascular beds. Me an arterial blood pressure fell from 86 +/- 4 to 94 +/- 4 mmHg (10%) ( P < 0.05). Splanchnic and renal blood flows fell by 43 +/- 3% (P < 0.0 5) and 29 +/- 4% (P < 0.05), respectively, during the infusion. Splanc hnic and renal vascular resistances rose by 92 +/- 22% (P < 0.05) and 58 +/- 7% (P < 0.05). In conclusion, ET-3 infusion in humans induces s planchnic and renal vasoconstriction of similar magnitude as previousl y shown during endothelin-1 infusion, presumably by ET(B) receptor act ivation. Plasma ET-3 is efficiently extracted in the splanchnic and re nal vascular regions.