Endothelin B receptor-deficient rats as a subtraction model to study the cerebral endothelin system.
Endothelins, due to their potent vasoactivity and mitogenicity, appear to play an important role in the brain, where all components of the endothelin system, peptides, receptors and converting enzyme, are expressed. To further elucidate the role of the cerebral endothelin system, astrocytes and cerebral vessels from sl/sl rats, devoid of functional endothelin B receptors, have been employed. Astrocytes from sl/sl rats display the following abnormalities as compared to wild-type (+/+) cells: (i) elevated basal extracellular endothelin-1 levels; (ii) exclusive presence of functional endothelin A receptors; (iii) increased extracellular endothelin-1 levels upon endothelin A receptor blockade; (iv) augmented basal endothelin-converting enzyme activity; (v) altered calcium response to endothelin-1. The basilar artery of sl/sl rats shows an enhanced constricting response to endothelin-1 and fails to dilate in response to endothelin-3, shifting the endothelin vasomotor balance to constriction. In conclusion, endothelin B receptors may be essential for restricting extracellular endothelin-1 levels in the brain, as well as for a balanced cerebral vasomotor action of endothelins.
Ehrenreich
H
H
Max-Planck-Institute for Experimental Medicine and Department of Neurology and Psychiatry, Georg-August-University, Göttingen, Germany.
Oldenburg
J
J
Hasselblatt
M
M
Herms
J
J
Dembowski
C
C
Löffler
B M
BM
Brück
W
W
Kamrowski-Kruck
H
H
Gall
S
S
Sirén
A L
AL
Schilling
L
L
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008666:Metalloendopeptidases; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000172:deficiency*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D002118:Calcium