Effects of deferoxamine and sympathectomy on endothelin-1-induced contraction and acetylcholine-induced relaxation following subarachnoid hemorrhage in carotid artery

The role of endothelium-related factors in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH) has gained interest since the discovery of EDRF and of endothelin (ET-1). The effect of SAH and both treatment of deferoxamine (DFO) and sympathectomy on endothelium dependent vasodilation and ET-l-induced vasoconstriction of isolated rabbit carotid artery was examined using an isometric tension recording method. Thirty-five rabbits were divided into four groups: control animals, 7 days after SAH, treatment with DFO after SAH for 7 days and sympathectomy after SAH. Acetylcholine (10(-8) to 10(-5) M) was used to evoke concentration dependent vasodilation of isolated arterial rings previously contracted by 10(-6) M phenylephrine. Tn the animals killed 7 days after SAH, acetylcholine induced relaxation was suppressed and the degree of relaxation of this group was 50% of the initial contractile tone in response to the 10(-5) M acetylcholine. These relaxant responses did not return to control values in carotid arteries obtained from animals treated with DFO and subjected to sympathectomy. In isolated carotid arteries, ET-1 (10(-10) to 10(-8) M) produced concentration-dependent contractions. These contractile responses were significantly enhanced in animals 7 days after SAH compared with controls and did not return to control values in carotid arteries obtained from animals both treated with DFO and sympathectomized for 7 days after SAH. The present experiments suggest that impairment of endothelium dependent vasodilation and the hyperreactivity of ET-1 of the carotid artery as well as cerebral arteries may be involved in the pathogenesis of cerebral vasospasm, Both treatment with DFO and sympathectomy during the chronic stage for vasospasm after SAH did not affect these vascular responses of the extradural part of the carotid artery to ET-1 and acetylcholine. Copyright (C) 1997 Elsevier Science Inc.