THE C-TERMINAL FRAGMENT OF BIG ENDOTHELIN-1 DOES NOT POTENTIATE THE VASOACTIVE EFFECTS OF ENDOTHELIN-1

The aim was to study the cardiovascular effects of the C-terminal (22- 38) fragment of big endothelin-1, which is produced by the cleavage of big endothelin-1 (big ET-1) to endothelin-1 (ET-1). An intravenous in fusion of the (22-38) fragment (4, 8 and 12 pmol kg(-1) min(-1), each dose for 10 min) was given to 10 healthy subjects. Four control subjec ts received 0.9% saline. Two additional subjects received ET-1 1 (0.2 and 4 pmol kg(-1) min(-1), each dose for 20 min) alone or combined wit h an equimolar infusion of the (22-38) fragment on two separate occasi ons. The fragment infusion did not alter heart rate, mean arterial blo od pressure, cardiac output, systemic or pulmonary vascular resistance , splanchnic, cerebral or forearm blood flow. Renal blood flow showed a slight fall (11%, P < 0.001) in the fragment group of the same magni tude as in a previous control study. After the fragment infusion, a de crease in mean pulmonary arterial pressure (MPAP) by 12% (P < 0.01) an d in pulmonary capillary wedge pressure (PCWP) by 31% (P < 0.001) was noted, which did not differ from the pulmonary pressures in the saline -infused control group. The (22-38) fragment, when combined with ET-1, was not able to modify the effects of ET-1 on heart rate, mean arteri al blood pressure, splanchnic and renal blood flow. Consequently, the exogenous (22-38) fragment does not seem to cause any significant card iovascular effects in healthy humans.