Artikel
Alteration of the contractile effect of serotonin in rat cerebral arteries during cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH)
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Veröffentlicht: | 20. Mai 2009 |
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Gliederung
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Objective: Cerebral vasospasm (CVS) remains to be one of the substantial causes for bad outcome after subarachnoid hemorrhage (SAH). Pathophysiological background may be the hyperreactivity of cerebral arteries to 5-hydroxytryptamine (5-HT). 5-HT is known to have a distinctive contractile effect in cerebral vessels. Furthermore, an up-regulation of the 5‑HT(1B)-receptor was detected after experimental SAH in correlation with the development of CVS. The aim of the present study was, therefore, to characterize an alteration of its contractile efficacy during experimental CVS.
Methods: Experimental CVS was induced by a rat double hemorrhage model. Autologous arterial blood was injected into the cisterna magna on day 1 and day 2. Rats were sacrificed on day 3 (d3) and day 5 (d5) after CVS induction. After dissecting the basilar arteries they were cut into ring segments. These segments were prepared for the measurement of isometric force in an organ bath.
Integrity of the endothelium and tunica media was tested functionally. Contraction is given in percent of 124 mM K+ force. Concentration-effect curves (CECs) were constructed in basilar artery ring segments by cumulative application of 5-HT. CECs were compared by the maximum effect (Emax), the pD2, and the shift calculated on the pD2 level (mean values [± standard error of the mean]). The pD2 is the negative decadic logarithm of the concentration producing the half maximal effect (-log10EC50). A p≤0.05 was considered statistically significant (*).
Results: Cumulative application of 5-HT induced a dose-dependent contraction in both kind of segments, obtained from controls and animals after SAH, The Emax was higher in all SAH groups compared to the control (control: 81±6%; d3: 109±6%; d5: 98±6 %) but only significant in the d3-group. The pD2 was also significantly altered in the d3-group (control: -6,698; d3:-7,019*; d5: -6,726). In the SAH groups a higher affinity (leftward shift) was observed (Shift vs. control: 2.13 (d3)*; 0.95 (d5)), which was significant for the d3-group.
Conclusions: The present data indicate a higher affinity to serotonin of rat basilar arteries after SAH. These higher potency and sensitivity suggest that 5-HT might have a potential role in early cerebral vasospasm after SAH. This contraction may be a further pathophysiological mechanism proceeding to the development of CVS.