Effects on feline pial arterioles in situ of bosentan, a non-peptide endothelin receptor antagonist.
The cerebrovascular actions of bosentan, a novel endothelin antagonist with effects at endothelin ETA and ETB receptors, have been examined in individual pial arterioles on the cortical surface of chloralose-anaesthetised cats. Subarachnoid perivascular microapplication of bosentan (0.3-300 microM) had minimal effect on pial arteriolar calibre. Subarachnoid perivascular microapplication of endothelin (10 nM) effected a marked reduction in pial arteriolar calibre (reduced by 39.2 +/- 2.7% from baseline). This vasomotor effect of topical endothelin could be attenuated either by co-administration of bosentan (IC50 approximately 1 microM) or by the intravenous administration of bosentan (17 mumol/kg). These investigations suggest that bosentan (applied topically or systemically) may be a valuable tool in the elucidation of the functional significance of endothelins in the cerebral circulation in vivo.
Patel
T R
TR
Wellcome Surgical Institute & Hugh Fraser Neuroscience Labs, University of Glasgow, UK.
McAuley
M A
MA
McCulloch
J
J
D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology / Q000187:drug effects; D000077300:Bosentan; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007267:Injections; D007275:Injections, Intravenous; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D013346:Subarachnoid Space; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D013449:Sulfonamides; D000077300:Bosentan