ENDOTHELIN RECEPTOR-MEDIATED CONSTRICTION AND DILATATION IN FELINE CEREBRAL RESISTANCE ARTERIOLES IN-VIVO

The receptors mediating the cerebrovascular actions of endothelins hav e been examined in feline cerebral resistance arterioles in vivo. The adventitial microapplication of the endothelin ET(A) receptor antagoni st BQ-123 (cycle partate-D-tryptophan-L-leucine-D-valine-L-proline) (0 .1-10 mu M) per se had minimal effect on cerebral resistance arteriole s examined. The adventitial microapplication of endothelin-1 (10 nM) e licited a marked vasoconstriction of cerebral resistance arterioles (- 29.1 +/- 1.9% from pre-injection baseline). The endothelin-1 induced vasoconstriction was attenuated, in a dose dependent manner, by the ad ventitial co-application of BQ-123 and endothelin-1 (estimated IC50 0. 7 mu M). The adventitial microapplication of the endothelin ET, recept or agonist BQ-3020 N-acetyl[Ala(11),Ala(15)]ET-1 (6-21)) (0.001-1 mu M ) effected a dose dependent vasodilatation (EC(50) 30 nM, maximum resp onse 25 +/- 15% from pre-injection baseline). The magnitude of the vas odilatation elicited by BQ-3020 (100 nM and 1 mu M) was dependent on t he pre-injection calibre of the arterioles examined. The intracarotid infusion (via the lingual artery) of BQ-3020 (0.5-500 pmol/min) had no significant effect on the calibre of cerebral resistance arterioles. These results suggest that the peptide endothelin ET(A) receptor agoni st fails to gain access to the cerebrovascular endothelin ET(A) recept ors following its intraluminal administration. These investigations in dicate that endothelin ET(A) receptors mediate vasoconstriction and en dothelin ET(A) receptors mediate vasodilatation in feline cerebral res istance arterioles in vivo.