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.