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
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.