CHANGES IN THE ADRENERGIC-MECHANISMS OF CEREBRAL-ARTERIES AFTER SUBARACHNOID HEMORRHAGE IN GOATS

WE HAVE EXAMINED the effects of experimental subarachnoid hemorrhage ( SAH), induced by delivering autologous blood into the subarachnoid spa ce, on the adrenergic mechanisms of the goat cerebrovascular bed. To a chieve this, the response to noradrenaline was recorded both in vivo, by measuring cerebral blood flow in unanesthetized animals, and in vit ro, by recording isometric tension in isolated cerebral arteries. In a ddition, we checked the function of adrenergic innervation by measurin g the tritium efflux evoked by electrical stimulation in cerebral arte ries preloaded with [H-3]-noradrenaline, and we examined this innervat ion by using both fluorescent and electron transmission microscopy. Al l studies were performed before and 3, 7, and 14 days after SAH. Injec tions of noradrenaline (0.1-10 mu g) directly into the cerebroarterial supply produced reductions in cerebral blood flow, with no concomitan t changes in mean arterial blood pressure and heart rate, which were s ignificantly enhanced (P< 0.01) 3 and 7 days after SAH and returned to control values 14 days after hemorrhage induction. In isolated cerebr al arteries, noradrenaline (10(-8)-10(-4) mol/L) produced concentratio n-dependent contractions, which were also significantly enhanced (P< 0 .05) 3 and 7 days after SAH and returned to control values in cerebral arteries obtained 14 days after SAH. On the other hand, increases in the release of tritium induced by electrical stimulation in cerebral a rteries preloaded with [H-3]-noradrenaline were significantly lower (P < 0.01) after SAH. Moreover, microscopical studies showed a reduction in catecholamine fluorescence and signs of sympathetic degeneration in some perivascular axons after SAH. These results show that SAH produc es sympathetic denervation of the cerebral arteries in the goat, which causes supersensitivity of the cerebrovascular bed to noradrenaline d uring the first week after SAH, and could contribute to develop cerebr al vasospasm. Down-regulation of cerebrovascular adrenergic receptors could explain the recovery of the normal sensitivity to noradrenaline during the second week after hemorrhage induction.