INTERACTIONS BETWEEN VASOCONSTRICTORS IN ISOLATED HUMAN CEREBRAL-ARTERIES

This study investigates whether different endogeneous vasoconstrictors exert synergistic effects in isolated human cerebral arteries, becaus e potentiation of contractile effects may play a role in the pathogene sis of cerebral vasospasm. Isolated human pial arteries obtained from macroscopically intact tissue during brain tumour operations were moun ted onto a wire myograph. Concentration-response curves of 5-hydroxytr yptamine (5-HT) were constructed in the absence and presence of thresh old concentrations of the thromboxane A(2) (TXA)-analog U46619, and en dothelin-1 (ET-1). Threshold concentrations of U46619 markedly enhance d the maximum contractile effect of 5-HT. The response to 5-HT remaine d markedly increased even after washout of U46619. Threshold concentra tions of ET-1 increased the maximum response to 5-HT, and markedly shi fted the dose-response curve to the left. Even after washout of ET-1, the dose-response curve of 5-HT remained shifted to the left. The incr ease of the contractile effect of 5-HT in the presence of U46619 did n ot correlate with the relaxant action of the endothelium-dependent vas odilalor carbachol. Thus, synergism between contractile substances suc h as 5-HT, U46619, or ET-1 is seen in human cerebral arteries, and res ponses to 5-HT are potentiated even after washout of ET-1 and U46619. The potentiation does not depend on the endothelial function. We concl ude that synergistic responses between endogeneous vasoconstrictors su ch as 5-HT, TXA and ET-1 may be involved in the pathogenesis of cerebr al vasospasm after subarachnoid haemorrhage.