Differential effects of chronic treatment with estrogen receptor ligands on regulation of nitric oxide synthase in porcine aortic endothelial cells

Hiroya Okano, Muthuvel Jayachandran, Akiko Yoshikawa, Virginia M. Miller

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

In cultured endothelial cells, estrogen increases expression and activity of endothelial nitric oxide synthase (eNOS). This study was designed to determine whether estrogenic treatments increase eNOS similarly in vivo. Aortic endothelial cells were collected from adult ovariectomized pigs which were untreated (8wk-OVX) or treated with oral 17β-estradiol (E2, 2 mg/day), conjugated equine estrogen (CEE, 0.625 mg/day), or raloxifene (60 mg/day) for 4 weeks. Plasma NOx, estrogen receptors (ERα and ERβ), eNOS, eNOS regulatory proteins, and eNOS mRNA in endothelial cells were determined by Griess reaction, Western blot, and real-time polymerase chain reaction, respectively. Ovariectomy decreased, whereas all treatments restored plasma NOx to pre-OVX levels. On the contrary, eNOS protein and mRNA increased with ovariectomy; E2 and CEE but not raloxifene reduced mRNA; eNOS protein was reduced by CEE and raloxifene treatments. Tyrosine phosphorylation of eNOS and expression of calmodulin increased, but Hsp90 decreased with all treatments and only raloxifene treatment increased caveolin-1 compared with OVX. Expression of ERα/ERβ increased with ovariectomy and was reversed by treatments such that raloxifene>CEE>E2. Three clinically relevant estrogen treatments restore plasma NO after ovariectomy, but do not affect eNOS mRNA, posttranslational regulation of eNOS or expression of estrogen receptors in the same way.

Original languageEnglish (US)
Pages (from-to)621-628
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume47
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • 17β-estradiol
  • Caveolin-1
  • Conjugated equine estrogen
  • Estrogen receptors
  • Raloxifene

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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