IMPAIRMENT OF THE MODULATORY ROLE OF NITRIC-OXIDE ON THE ENDOTHELIN-1-ELICITED CONTRACTION OF CEREBRAL-ARTERIES - A PATHOGENETIC FACTOR IN CEREBRAL VASOSPASM AFTER SUBARACHNOID HEMORRHAGE

OBJECTIVE: Nitric oxide (NO) and endothelin-l (ET-1) are two endotheli um-derived factors probably involved in the pathogenesis of cerebral v asospasm after subarachnoid hemorrhage (SAH). Our aim was twofold, i.e ., to ascertain whether endothelial and nonendothelial NO modulates th e contractile response of cerebral arteries to ET-1 and to analyze whe ther this relationship might be impaired after experimental SAH. METHO DS: Rings of middle cerebral artery from goats in the control group an d from goats with SAH were set up for isometric tension recordings. SA H was induced 3 days before the experiments by infusion of 10 mi of au tologous arterial blood through a catheter previously inserted into th e subarachnoid space (basal cistern). In goats in the control group, t he response to ET-1 was obtained as follows: 1) in control arteries (u nrubbed and nonincubated arteries); 2) in rubbed arteries (arteries in which the endothelium was mechanically removed); 3) during incubation with N-G-nitro-L-arginine (L-NOArg) alone or plus L- or D-arginine; a nd 4) in rubbed arteries plus incubation with L-NOArg. In goats with S AH, that response was obtained in control arteries, rubbed arteries, a nd during incubation with L-NOArg. Specimens of middle cerebral artery were processed for transmission electron microscopy study. RESULTS: I n goats in the control group, ET-1 elicited concentration-dependent co ntraction of the middle cerebral artery that was significantly potenti ated after endothelium denudation or during incubation with L-NOArg. T he latter effect was reversed by L-arginine but not by D-arginine. Com bined endothelium denudation and incubation with L-NOArg produced a co ntractile response to ET-1 significantly higher than that induced by e ach treatment separately. Hyperreactivity to ET-1 was observed in goat s with SAH. Endothelium denudation did not alter the enhanced response to ET-1, but it was further significantly increased after incubation with L-NOArg. CONCLUSION: These results demonstrate that an ET-1-NO in teraction exists in control cerebral arteries in such a way that endot helial and nonendothelial NO partially counteract the contractile resp onse to ET-1 and that although SAH did not modify the effect of nonend othelial NO, the absence of endothelial NO after SAH may contribute to the hyperreactivity of cerebral arteries to ET-1 and, thereby, to the development of cerebral vasospasm.