Objective: The objective of this study was to determine whether the long-term administration of an HMG-CoA reductase inhibitor, atorvastatin, confers antioxidative effect in microvessels in the brain of stroke-prone spontaneously hypertensive rats (SHRSPs). Method: Atorvastatin (20 mg/kg) or vehicle was orally administered to 8-week-old SHRSPs for 5 weeks. As normal controls, vehicle was orally administered to 8-week-old WKYs over the same period. The animals were decapitated and the brains were removed. The brains were then quickly frozen, and were sliced into horizontal sections of 6-mm-thickness using a cryostat. The markers for oxidative stresses on lipids (4HNE) and DNA (8OHdG) were immunohistochemically detected. The numbers of positive vessels in the 6 randomized 0.25 mm 2 areas in a horizontal section were counted. The ratio of positive vessels for each maker to all vessels (positive for von Wille brand factor) was calculated.Results: The positive ratio of oxidative stress markers was significantly higher in the vehicle group than in the normal controls. Then the positive ratio was significantly lower in the atorvastatin group than in the vehicle group. Atorvastatin significantly reduced immunoreactivities for oxidative stress markers in microvessels. Lipids such as total cholesterol (T-cho), HDL-cholesterol (HDL-cho), LDL-cholesterol (LDL-cho), and triglyceride (TG) did not differ among the vehicle, the statin, and normal control groups.
Conclusions:The results suggest that statins may confer the antioxidative properties and have the protective effects in the endothelial cells, even in the brain microvessels.35. Concomitant treatment with medroxyprogesterone and conjugated equine estrogens attenuates estrogen's protective effect on postischemic pial artery vasodilation to acetylcholine C. Miyazaki 1 , E. Zeynalov 1 and M. LIttleton-Kearney 2 1 Anesthesia/Critical Care Medicine; 2 Nursing/Anesthesia Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA Background and aims: Chronic estrogen replacement partially preserves postischemic pial arteriole vasodilation to endothelium-dependent vasodilators. It is unclear if concomitantly administered equine estrogens (EE) and medroxyprogesterone (MP), hormone replacement therapy commonly prescribed for women, alters estrogen's effect on postischemic pial arterial vasodilation. We determined if:(1) EE preserves postischemic pial artery dilation to acetylcholine (Ach), (2) concomitant administration of MP and EE alters the effect of EE alone on postichemic Ach-evoked dilation, (3) natural hormone depletion associated with aging depresses postischemic pial artery Ach-evoked dilation, and (4) concomitantly administered EE and MP has the same effect on postischemic pial artery dilation in young ovariectomized (OVX) and aged reproducively senescent rats (RS).Methods: Young OVX (2 to 3.5 months) or aged RS female rats (20 to 22 months) were used for these studies. The young groups included; OVX, EE-treated (EE) and EE plus MP (EEMP). The aged group...