17beta-estradiol inhibits endothelin-1 production and attenuates cerebral vasospasm after experimental subarachnoid hemorrhage.
Though cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) has been recognized for over half a century, it remains a major complication in patients with SAH. Clinical studies have shown that elevated levels of endothelin-1 (ET-1) are present in the cerebrospinal fluid of patients with SAH, suggesting that ET-1-mediated vasoconstriction contributes to vascular constriction after SAH. Administration of estrogen promotes vasodilation in humans and in experimental animals, in part by decreasing the production of ET-1. This study evaluated the influence of 17beta-estradiol (E2) on the production of ET-1 and cerebrovasospasm in an experimental SAH 2-hemorrhage model in rat. A 30-mm Silastic tube filled with E2 in corn oil (0.3 mg/ml) was subcutaneously implanted in male rats just before SAH induction. The degree of vasospasm was determined by averaging the cross-sectional areas of basilar artery 7 days after first SAH. Plasma samples collected before death were assayed for ET-1. The protective effect of E2 in attenuating vasospasm achieved statistical significance when compared with the SAH only or SAH plus vehicle groups (P < 0.01). Concentrations of ET-1 were higher in the SAH only and SAH plus vehicle groups than in controls (P < 0.001). Serum levels of ET-1 in the SAH plus E2 and E2 only groups were significantly lower than those in the SAH only and SAH plus vehicle groups (P < 0.001). There was no significant difference between ET-1 levels in the healthy control and SAH plus E2 groups. A significant correlation was found between the cross-sectional areas of basilar artery and ET-1 levels (P < 0.001). The beneficial effect of E2 in attenuating SAH-induced vasospasm may be due in part to decreasing ET-1 production after SAH. The role of E2 in the treatment of cerebral vasospasm after SAH is promising and is worthy of further investigation.
Lin
Chih-Lung
CL
Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan, Republic of China.
Dumont
Aaron S
AS
Wu
Shu-Chuan
SC
Wang
Chih-Jen
CJ
Howng
Sheng-Long
SL
Huang
Yan-Fen
YF
Wong
Wee-Yen
WY
Kassell
Neal F
NF
Jeng
Arco Y
AY
Kwan
Aij-Lie
AL
D000818:Animals; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000037:antagonists & inhibitors*; D004958:Estradiol / Q000627:therapeutic use*; D002532:Intracranial Aneurysm / Q000150:complications; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000209:etiology*; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology
D019332:Endothelin-1; D004958:Estradiol