Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 21, Issue 8, Pages 907-913Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00004647-200108000-00002
Keywords
17 beta-estradiol; acetylcholine; antisense oligonucleotide; nitric oxide; simvastin
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Funding
- NHLBI NIH HHS [HL 56162, HL 52594] Funding Source: Medline
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The marked impairment in cerebrovascular endothelial nitric oxide synthase (eNOS) function that develops after ovariectomy may relate to the observation that the abundance of cerebral vascular eNOS and its endogenous inhibitor, caveolin-1, vary in opposite directions with chronic changes in estrogen status. The authors endeavored, therefore, to establish a link between these correlative findings by independently manipulating, in ovariectomized female rats, eNOS and caveolin-1 expression, while monitoring agonist (acetylcholine)stimulated eNOS functional activity. In the current study, the authors showed that individually neither the up-regulation of eNOS (through simvastatin treatment), nor the down-regulation of caveolin-1 (through antisense oligonucleotide administration) is capable of restoring eNOS function in pial arterioles in vivo in these estrogen-depleted rats. Only when eNOS upregulation and caveolin-1 down-regulation are combined is activity normalized. These results establish a mechanistic link between the estrogen-associated divergent changes in the abundance of caveolin-1 and eNOS protein and eNOS functional activity in cerebral arterioles.
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