THE VASOINHIBITORY ACTIVITY OF BOVINE CHROMOGRANIN-A FRAGMENT (VASOSTATIN) AND ITS INDEPENDENCE OF EXTRACELLULAR CALCIUM IN ISOLATED SEGMENTS OF HUMAN BLOOD-VESSELS

Endothelium-independent vasoconstrictor responses in isolated segments of human internal thoracic artery (ITA) and saphenous vein (SV) were used as a bioassay system for the vasoinhibitory activity of bovine chromogranin A (CGA). Preincubation with vasostatin (0.8-mu-g/ml), containing the N-terminal domain of CGA, (CGA1-76, CGA1-113 and CGA1-143ff), inhibited the contractile responses evoked by 80 mM K+, 2.6-mu-M noradrenaline (NA), or 65 nM endothelin-1 (ET-1) in Ca2+,-free solution in SV but not in ITA. The results demonstrate a vasoinhibitory activity in vasostatin and show that there is a marked difference between the arterial and venous segments in the Ca2+, independent component of the inhibitory response. A vascular role for the N-terminal domain of CGA is indicated, presumably by inhibiting Ca2+ release from intracellular stores in the human vein but not the artery.