Effect of estrogen therapy on cerebral arteries during stroke in female rats

Gwen J Goodrow, Lisa Vitullo, Marilyn J Cipolla
Menopause: the Journal of the North American Menopause Society 2005, 12 (1): 99-109

OBJECTIVE: To investigate the effect of estrogen therapy on the structural and functional properties of the middle cerebral artery during ischemia and reperfusion.

DESIGN: Ovariectomized (OVX; n = 8) and ovariectomized with estrogen therapy (OVX+EST; n = 8) female Sprague-Dawley rats were exposed to 1 hour of ischemia using a model of temporary focal ischemia of the middle cerebral artery with 24 hours of reperfusion and compared to sham controls (CTL; n = 8). After occlusion and reperfusion, right middle cerebral arteries were removed from the brain and mounted on glass cannulas in a chamber that allowed for control over transmural pressure and measurement of lumen diameter. Lumen diameter was measured in response to increased transmural pressure (myogenic tone) as well as response to nitro-L-arginine, serotonin, and nifedipine. Cerebrovascular reactivity was compared to other stroke outcome measures, including infarct volume (%) and neurologic deficit.

RESULTS: Serum estrogen was increased in OVX+EST rats (60.5 +/- 18.2 pg/mL) compared to OVX (0.2 +/- 0.2 pg/mL P < 0.05 vs OVX+EST) and CTL animals (1.3 +/- 1.0 pg/mL P > 0.05 vs OVX). OVX showed significantly less myogenic tone at 75 mm Hg (13.8 +/- 3.6%, P < 0.05 vs CTL) than CTL (29.8 +/- 4.7%) that was partially restored by estrogen therapy (21.2 +/- 4.5; P > 0.05). At serotonin concentrations of 10(-7) M, 3 x 10(-7) M, and 10(-6) M, the vessels from ischemic OVX rats showed significantly greater constriction (20.9 +/- 2.1%, 35.0 +/- 3.9%, and 39.4 +/- 3.4%, respectively) compared to nonischemic CTL rats (6.3 +/- 1.1%, 11.3 +/- 1.8%, and 16.8 +/- 2.5%, respectively P < 0.05). Estrogen therapy resulted in intermediate responses (18.2 +/- 5.3%, 25.2 +/- 6.6%, and 28.2 +/- 6.5%, respectively) that were not significantly different from the other groups. In addition, ischemia resulted in significantly greater dilation in response to 0.01 microM nifedipine in vessels from OVX animals (51.1 +/- 8.0%) compared to nonischemic CTL (18.0 +/- 3.8%; P < 0.05) and estrogen therapy resulted in an intermediate response (38.0 +/- 10.6; P > 0.05). Both reactivity to nitro-L-arginine and passive distensibility were not different among groups. There were no differences in percent infarct or neurologic deficit between ischemic groups.

CONCLUSIONS: The influence of ischemia and reperfusion on vessel function was more dominant than that of estrogen therapy. However, estrogen therapy seemed to partially restore vessel function to similar levels as nonischemic vessels.

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