HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Konczalla, J. Articles by Seifert, V. Search for Related Content PubMed PubMed Citation Articles by Konczalla, J. Articles by Seifert, V.

---

CENTRAL NERVOUS SYSTEM

Alteration of the Cerebrovascular Function of Endothelin B Receptor After Subarachnoidal Hemorrhage in the Rat

Department of Neurosurgery and Institute of Neuroradiology, Johann Wolfgang Goethe-University, D-60528 Frankfurt am Main, Germany

To whom requests for reprints should be addressed at ¹ Schleusenweg2–16, Frankfurt am Main D-60528, Germany. E-mail: H.Vatter{at}em.uni-frankfurt.de

Abstract

The substantial role of endothelin-1 (ET-1) in the development of cerebral vasospasm (CVS) after subarachnoidal hemorrhage (SAH) has been demonstrated by numerous experimental and, recently, clinical investigations. Whether the expression or function of the ET(B) receptor is altered in CVS is still unclear, however. The aim of the present study was, therefore, to characterize the cerebroarterial ET(B) receptor function during CVS. Experimental CVS was induced by the rat double-hemorrhage model. Reduction of the cerebral blood flow (CBF) was confirmed by magnetic resonance perfusion-weighted imaging. Animals were sacrificed on days 3 (d3) and 5 (d5) after CVS induction. The basilar arteries (BA) were dissected, cut into ring segments, and prepared for measurement of isometric force in an organ bath. Concentration-effect curves (CECs) were constructed by cumulative application of ET-1, acetylcholine (Ach), or sarafotoxin S6c (S6c). Segments with (E+) endothelial function were used. CECs were compared by the maximum effect (E_max), the pD_2, and the shift calculated on the pD₂ level. The pD₂ is the negative decadic logarithm of the concentration producing the half maximal effect (–log₁₀EC₅₀). After SAH, the relative regional CBF in the d3 and d5 groups was reduced to 63% and 32%, respectively, of the CBF in controls. ET-1 induced a dose-dependent contraction of segments with and segments without CVS. In E+ segments, the E_max for ET-1 was not significantly changed after SAH (mean values [ ± SEM] of 104% ± 4% for the control group, 106% ± 4% for the d3 group, and 104% ± 3% for the d5 group). The CECs, however, were significantly shifted to the left versus the control by factors of 2.4 in the d3 group and 3.6 in the d5 group. Relaxation by S6c was significantly reduced after SAH (E_max: 73% ± 11% in the control group, 21% ± 13% in the d3 group, and 13% ± 8% in the d5 group), whereas relaxation associated with Ach was not significantly changed (E_max: 45% ± 7% in the control group, 56% ± 6% in the d3 group, and 43% ± 6% in the d5 group). Significant contraction by S6c was not observed in E+ and E – segments in any of the study groups. The present data indicate the loss of the ET(B) receptor–mediated relaxation of the cerebral arteries in cases of CVS, which is independent of the endothelial nitric oxide synthase level.

Key Words: rat • double hemorrhage model • vasospasm • subarachnoidal hemorrhage • endothelin-1 • endothelin (B)-receptor • Sarafotoxin S6c • endothelium-dependent relaxation

This article has been cited by other articles:

				N. Toda, K. Ayajiki, and T. Okamura Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances Pharmacol. Rev., March 1, 2009; 61(1): 62 - 97. [Abstract] [Full Text] [PDF]