HUMAN CHROMOSTATIN INHIBITS ENDOTHELIN-1-INDUCED CONTRACTURES IN HUMAN BLOOD-VESSELS

Isolated endothelium-denuded segments of the human internal thoracic artery (ITA) and saphenous vein (SV) have been used for characterization of vasoinhibitory effects of the chromostatin (hChs) sequence of human chromogranin A (CGA124-143). In SV preincubation with hChs inhibited the response to depolarizing high K+ in Ca2+-free medium in a concentration dependent manner (EC50 approximately 2 nM). At 200 nM hChs the tension response to high K+ (80 mM) was inhibited by 44% (n = 8) and the tension response to noradrenaline (2.6 muM) was inhibited by 20% (n = 6), but the tension response to endothelin-1 (65 nM) (ET-1) was not affected. In ITA no effect of hChs was observed on tension response to K+ or ET-1 in Ca2+-free medium. On the other hand, in Ca2+-containing medium the tension evoked by 65 nM ET-1 was no longer sustained in segments preincubated with 200 nM hChs and declined spontaneously to 76 +/- 12% (n = 6) of maximal tension after 6 min. A vascular function for the Chs sequence of the human CGA is thus indicated, inhibiting different components of vasoconstrictor responses in the human SV and ITA segments.