Nitric-oxide-dependent pial arteriolar dilation in the female rat: Effectsof chronic estrogen depletion and repletion

In this study, we compared endothelial nitric oxide synthase (eNOS)-mediate d cerebral vasodilating responses in intact female rats, chronically ovarie ctomized (OVX) rats, and OVX rats treated for 2 weeks with 17 beta-estradio l (E-2). Under anesthesia, using intravital microscopy and a closed cranial window system, pial arteriolar diameter changes were monitored during sequ ential cortical suffusions of an eNOS-dependent dilator [acetylcholine (ACh )] and a direct NO donor [S-nitrosoacetylpenicillamine (SNAP)]. In separate rats from the same groups, we compared eNOS and caveolin-1 (CAV-1) protein abundance in pial arterioles (via immunofluorescence analyses). In untreat ed and low-dose E-2-treated (1.0 mu g.kg(-1).day(-1)) OVX rats, ACh-induced vasodilations were virtually absent. High-dose E-2 treatment (100 mu g.kg( -1).day(-1)) restored ACh-induced pial arteriolar dilations to levels seen in intact females. The vasodilations elicited by SNAP and ADO were unaffect ed by chronic estrogen changes, indicating no direct estrogen influence on vascular smooth muscle (VSM) reactivity. Pial arteriolar eNOS protein abund ance was diminished by ovariectomy and restored by high-dose E-2 treatment. Pial arteriolar CAV-1 expression was higher in OVX versus intact and E-2-t reated OVX females. These results suggest that long-term changes in estroge n directly influence brain eNOS functional activity. The estrogen-related c hanges in eNOS-dependent vasodilating function appear to be related, in par t, to a capacity for E-2 to increase eNOS protein expression and, in part, to an E-2-associated diminution in endothelial CAV-1 expression. (C) 2000 A cademic Press.