Endothelin B receptor-deficient rats as a subtraction model to study the cerebral endothelin system

Citation
H. Ehrenreich et al., Endothelin B receptor-deficient rats as a subtraction model to study the cerebral endothelin system, NEUROSCIENC, 91(3), 1999, pp. 1067-1075
Citations number
46
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROSCIENCE
ISSN journal
03064522 → ACNP
Volume
91
Issue
3
Year of publication
1999
Pages
1067 - 1075
Database
ISI
SICI code
0306-4522(1999)91:3<1067:EBRRAA>2.0.ZU;2-V
Abstract
Endothelins, due to their potent vasoactivity and mitogenicity, appear to p lay an important role in the brain, where all components of the endothelin system, peptides, receptors and converting enzyme, are expressed. To furthe r elucidate the role of the cerebral endothelin system, astrocytes and cere bral vessels from sl/sl rats, devoid of functional endothelin B receptors, have been employed. Astrocytes from sl/sl rats display the following abnorm alities as compared to wild-type (+/+) cells: (i) elevated basal extracellu lar endothelin-1 levels; (ii) exclusive presence of functional endothelin A receptors; (iii) increased extracellular endothelin-1 levels upon endothel in A receptor blockade; (iv) augmented basal endothelin-converting enzyme a ctivity; (v) altered calcium response to endothelin-1. The basilar artery o f sl/sl rats shows an enhanced constricting response to endothelin-1 and fa ils to dilate in response to endothelin-3, shifting the endothelin vasomoto r balance to constriction. In conclusion, endothelin B receptors may be essential for restricting extr acellular endothelin-1 levels in the brain, as well as for a balanced cereb ral vasomotor action of endothelins. (C) 1999 IBRO. Published by Elsevier S cience Ltd.