EFFECTS ON FELINE PIAL ARTERIOLES IN-SITU OF BOSENTAN, A NONPEPTIDE ENDOTHELIN RECEPTOR ANTAGONIST

The cerebrovascular actions of bosentan, a novel endothelin antagonist with effects at endothelin ET(A) and ET(B) receptors, have been exami ned in individual pial arterioles on the cortical surface of chloralos e-anaesthetised cats. Subarachnoid perivascular microapplication of bo sentan (0.3-300 mu M) had minimal effect on pial arteriolar calibre. S ubarachnoid perivascular microapplication of endothelin (10 nM) effect ed 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 approxima tely 1 mu M) or by the intravenous administration of bosentan (17 mu m ol/kg). These investigations suggest that bosentan (applied topically or systemically) may be a valuable tool in the elucidation of the func tional significance of endothelins in the cerebral circulation in vivo .