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Submitted on April 20, 2006
From the Departments of Neurology, Obstetrics/Gynecology, and Pharmacology, University of Vermont, Burlington. * To whom correspondence should be addressed. E-mail: Marilyn.Cipolla{at}uvm.edu.
Abstract--Eclampsia is considered a form of hypertensive encephalopathy in which an acute elevation in blood pressure causes autoregulatory breakthrough, blood-brain barrier disruption, and edema formation. We hypothesized that pregnancy predisposes the brain to eclampsia by lowering the pressure of autoregulatory breakthrough and enhancing cerebral edema formation. Because NO production is increased in pregnancy, we also investigated the role of NO in modulating autoregulation. Cerebral blood flow autoregulation was determined by phenylephrine infusion and laser Doppler flowmetry. Four groups were studied: untreated nonpregnant (n=7) and late-pregnant (days 19 to 21; n=8) Sprague-Dawley rats and nonpregnant (n=8) and late-pregnant (n=8) animals treated with an NO synthase inhibitor (NG-nitro-L-arginine methyl ester; 0.5 to 0.7 g/L). Brain water content and blood-brain barrier permeability to sodium fluorescein were determined after breakthrough. Pregnancy caused no change in autoregulation or the pressure of breakthrough. However, treatment with the NO synthase inhibitor significantly increased the pressure of autoregulatory breakthrough (nonpregnant: 183.6±3.0 mm Hg versus 212.0±2.8 mm Hg, P<0.05; late-pregnant: 180.8±3.2 mm Hg versus 209.3±4.7 mm Hg, P<0.05). After autoregulatory breakthrough, only late-pregnant animals showed a significant increase in cerebral edema formation, which was attenuated by NO synthase inhibition. There was no difference in blood-brain barrier permeability between nonpregnant and late-pregnant animals in response to acute hypertension, suggesting that pregnancy may predispose the brain to eclampsia by increasing cerebral edema through increased hydraulic conductivity.
Revised on May 11, 2006
Cerebral Blood Flow Autoregulation and Edema Formation During Pregnancy in Anesthetized Rats
Anna G. Euser and Marilyn J. Cipolla*
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