Artikel
Functional characterization of the contractile effect of Endothelin-1 and the Endothelin converting enzyme activity of cerebral arteries in case of vasospasm
Funktionelle Charakterisierung der kontraktilen Wirkung von Endothelin-1 und der Endothelin-converting-enzym-Aktivität zerebraler Arterien während eines Vasospasmus
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Autoren
Veröffentlicht: | 23. April 2004 |
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Gliederung
Text
Objective
An upregulation of the cerebral Endothelin (ET)-system after subarachnoid hemorrhage (SAH) is considered a major pathophysiological factor for the development of cerebral vasospasm (CVS). However, data characterizing the altered effects of ET-1 or the Endothelin converting-enzyme (ECE) of cerebral vessels after SAH are scarce. The aim of the present study was, therefore, to characterize the contractile effect of ET-1 and its precursor bigET-1 on cerebral arteries in case of CVS.
Methods
CVS was induced in a double hemorrhage model (application of 0.2 ml autologous blood in the Cisterna magna) in male Sprague-Dawley rats and was proofed by angiography and perfusion weighted MR-scan. Animals were sacrificed on day 7 and the basilar artery (BA) was dissected meticulously. Ring segments from the BA were prepared for the measurement of isometric force in an organ bath. Concentration-effect curves (CECs) were constructed by cumulative application of ET-1 or bigET-1.
Results
A dose dependent contraction of BA ring segments with and without CVS was induced by ET-1 and bigET-1. The pD2-values for ET-1 did not differ significantly. The E(max), however, was significantly higher in case of CVS (SAH: 126±8%, control: 105±12%). Similarly, E(max) for bigET-1 was significantly enhanced after SAH (SAH: 125±12%, control: 97±14%). The pD2-value for bigET-1, in contrast, was significantly reduced in case of CVS (SAH: 6.71±0.06, control: 7.06±0.17).
Conclusions
An enhanced contractile effect of ET-1 and bigET-1 on cerebral vessels in case of CVS in indicated by the present results, supporting the important role of the ET-system in the development of CVS. Furthermore, our data suggest a reduced functional ECE-activity in cerebral vessels, after SAH.