Object: Sex differences in the outcome of aneurysmal subarachnoid hemorrhage (SAH) are controversial, and the potential influence of estradiol on vasodilation is unclear. In the present study the authors evaluate the effect and possible mechanism of 17beta-estradiol (E2) on SAH-induced vasospasm in a two-hemorrhage rodent model of SAH.
Methods: A 30-mm Silastic tube filled with E2 in corn oil (0.3 mg/ml) was subcutaneously implanted in male rats. Serum levels of E2 were measured on Days 0, 1, 2, 3, 4, and 7 postimplantation. The degree of vasospasm was determined by averaging the cross-sectional areas of the basilar artery (BA) 7 days after the first SAH. Expressions of endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) in the BA were also evaluated. Serum levels of E2 in the E2-treated rats were at physiological levels (56-92 pg/ml) and were significantly higher than those in the control and vehicle-treated groups. Treatment with E2 significantly (p < 0.01) attenuated SAH-induced vasospasm. Induction of iNOS messenger (m)RNA and protein in the BA by SAH was significantly diminished by the E2 treatment but not by vehicle treatment. The SAH-induced suppression of eNOS mRNA and protein was relieved by E2 treatment.
Conclusions: These results suggest that continuous treatment with E2 at physiological levels prevents cerebral vasospasm following SAH. The beneficial effect of E2 may be in part related to the prevention of augmentation of iNOS expression and the preservation of normal eNOS expression after SAH. Treatment with E2 holds therapeutic promise in the treatment of cerebral vasospasm following SAH and merits further investigation.