CONSTRICTION DILATATION OF THE CEREBRAL MICROVESSELS BY INTRAVASCULARENDOTHELIN-1 IN CATS/

The effects of intracarotidly injected endothelin (ET)-1 (0.01-3 nmol) on the local cerebral blood volume (CBV) in the parietotemporal corte x were examined by the photoelectric method in 17 anesthetized cats. C BV reflects the cumulative dimensions of the cerebral microvessels. Lo w doses of ET-1 (0.01 and 0.1 nmol) elicited mild but significant redu ctions in CBV without changes in the systemic arterial blood pressure (SABP). High doses of ET-1 (3 nmol) initially induced marked declines of CBV, which were attributable to the significant falls in SABP. CBV subsequently exhibited significant increases. The CBV increases were n ot secondary to the accompanying elevations of SABP, since they were u naffected by inhibition of the SABP changes after preinjection of BQ-1 23 (1 mg/kg), an ET antagonist specific to the ET(A) receptors. The CB V increases, however, were prevented by continuous administration of N -G-monomethyl-L-arginine (0.35 mg/kg/min), an inhibitor of nitric oxid e synthesis, plus BQ-123. We conclude that while low doses of intravas cular ET-1 constrict the cerebral microvessels, high doses of ET-1 dil ate the cerebral microvessels through the induction of nitric oxide pr obably in the cerebrovascular endothelium.