Nitric-Oxide-Dependent Pial Arteriolar Dilation in the Female Rat: Effects of Chronic Estrogen Depletion and Repletion

Estrogen and Cerebrovascular Physiology and Pathophysiology

“…Regulation of eNOS expression: Additional investigations, albeit limited in number (see Table 1), have examined the effects of chronic estrogen depletion and repletion on cerebral eNOS expression. The general conclusion from these studies is that, like most of the investigations directed toward peripheral vascular tissue (see above), chronic reductions in circulating estrogen (via ovariectomy) are associated with diminished cerebrovascular eNOS protein abundance, while E 2 replacement restores eNOS (80,82). The E2-related effect on eNOS appears to exhibit a rather complex regional selectivity, with pial and striatal eNOS expression being reduced by ovariectomy and restored by E2 replacement, while in the hippocampus, no variations in eNOS were seen (Fig.…”

“…Results from our laboratory revealed that chronic estrogen depletion, via ovariectomy, in rats was accompanied by a loss of eNOS-dependent (i.e., ACh-induced) vasodilating function in pial arterioles, but those changes could be prevented with 1 -2 weeks of E2 replacement (80). In a preliminary study (81), we also found that the changes in eNOS-dependent cerebral vasodilation associated with chronic estrogen status exhibited a regional selectivity, with results for the cortex and striatum, but not the hippocampus, mirroring those in pial arterioles (Fig.…”

“…These include cofactors; L-arginine transporters (89); proteins regulating Ca 2+ influx, extrusion and intracellular release (90); and even muscarinic receptors (91). In a recent publication, Feron et al (92) found that upregulation of 78,80,177,178). In the lower panel, the levels of eNOS protein are expressed in relation to a HUVEC standard (control) run with each gel (not shown).…”

“…That mechanism could be linked to estrogen by virtue of evidence provided in multiple studies showing that brain neurotrophin and tyrosine kinase receptor expression appear to vary directly with long-term estrogen changes (103 -106). Furthermore, E2 was recently A rabbit polyclonal antibody (from Transduction Laboratories) was used for this assay (80). In each case, the selectivity of the antibody was confirmed by the fact that only a single band (at 22 -24 kDa) was visible.…”

Caveolin, Caveolae, and Endothelial Cell Function

“…64 In agreement with this finding, long-term estrogen depletion after ovariectomy is accompanied by an upregulation of (cerebral) endothelial caveolin-1 expression in vivo. 65,66 Ion Channel Regulation Several ion channels have been shown to be associated with caveolae (Table). These channels play a very important role in the regulation of endothelial barrier functioning, because they are involved in the regulation of endothelial cell permeability, transcytosis, angiogenesis, and the response to shear stress.…”