Effect of estrogen on cerebrovascular prostaglandins is amplified in mice with dysfunctional NOS

Xiangduan Li, Greg G. Geary, Rayna J. Gonzales, Diana N. Krause, Sue P. Duckles

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Chronic estrogen treatment increases endothelial vasodilator function in cerebral arteries. Endothelial nitric oxide (NO) synthase (eNOS) is a primary target of the hormone, but other endothelial factors may be modulated as well. In light of possible interactions between NO and prostaglandins, we tested the hypothesis that estrogen treatment increases prostanoid-mediated dilation using NOS-deficient female mouse models, i.e., mice treated with a NOS inhibitor [NG-nitro-L-arginine methyl ester (L-NAME)] for 21 days or transgenic mice with the eNOS gene disrupted (eNOS-/-). All mice were ovariectomized; some in each group were treated chronically with estrogen. Cerebral blood vessels then were isolated for biochemical and functional analyses. In vessels from control mice, estrogen increased protein levels of eNOS but had no significant effect on cyclooxygenase (COX)-I protein, prostacyclin production, or constriction of pressurized, middle cerebral arteries to indomethacin, a COX inhibitor. In L-NAME-treated mice, however, cerebrovascular COX-1 levels, prostacyclin production, and constriction to indomethacin, as well as eNOS protein, were all greater in estrogen-treated animals. In vessels from eNOS-/- mice, estrogen treatment also increased levels of COX-1 protein and constriction to indomethacin, but no effect on prostacyclin production was detected. Thus cerebral blood vessels of control mice did not exhibit effects of estrogen on the prostacyclin pathway. However, when NO production was dysfunctional, the impact of estrogen on a COX-sensitive vasodilator was revealed. Estrogen has multiple endothelial targets; estrogen effects may be modified by interactions among these factors.

Original languageEnglish (US)
Pages (from-to)H588-H594
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number2 56-2
DOIs
StatePublished - Aug 2004

Keywords

  • Cyclooxygenase-1
  • Endothelial nitric oxide synthase
  • Indomethacin
  • N-nitro-L-arginine methyl ester
  • Prostacyclin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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