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Interactions between vasoconstrictors in isolated human cerebral arteries

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Summary

This study investigates whether different endogeneous vasoconstrictors exert synergistic effects in isolated human cerebral arteries, because potentiation of contractile effects may play a role in the pathogenesis of cerebral vasospasm.

Isolated human pial arteries obtained from macroscopically intact tissue during brain tumour operations were mounted onto a wire myograph. Concentration-response curves of 5-hydroxytryptamine (5-HT) were constructed in the absence and presence of threshold concentrations of the thromboxane A2 (TXA)-analog U46619, and endothelin-1 (ET-1).

Threshold concentrations of U46619 markedly enhanced the maximum contractile effect of 5-HT. The response to 5-HT Threshold concentrations of ET-1 increased the maximum response to 5-HT, and markedly shifted 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 increase of the contractile effect of 5-HT in the presence of U46619 did not correlate with the relaxant action of the endothelium-dependent vasodilator carbachol.

Thus, synergism between contractile substances such as 5-HT, U46619, or ET-1 is seen in human cerebral arteries, and responses to 5-HT are potentiated even after washout of ET-1 and U46619. The potentiation does not depend on the endothelial function. We conclude that synergistic responses between endogeneous vasoconstrictors such as 5-HT, TXA and ET-1 may be involved in the pathogenesis of cerebral vasospasm after subarachnoid haemorrhage.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Kiel, Kiel, Federal Republic of Germany

    R. G. Hempelmann, H. L. Barth & H. M. Mehdorn

  2. Department of Pharmacology, University of Kiel, Kiel, Federal Republic of Germany

    R. H. E. Pradel & A. Ziegler

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  1. R. G. Hempelmann
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Hempelmann, R.G., Pradel, R.H.E., Barth, H.L. et al. Interactions between vasoconstrictors in isolated human cerebral arteries. Acta Neurochir 139, 574–582 (1997). https://doi.org/10.1007/BF02751003

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