Compromised aortic vasoreactivity in male estrogen receptor-α- deficient mice during acute lipopolysaccharide-induced inflammation

Ana M. Corbacho, Jason P. Eiserich, Luis A. Zuniga, Giuseppe Valacchi, Amparo C Villablanca

Research output: Contribution to journalArticle

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Abstract

Activation of the estrogen receptor-α (ERα) mediates the vasculoprotective effects of estrogen, in part, through modulating nitric oxide (NO) production and vasodilation. Whereas inflammation is accompanied by altered vascular reactivity and underlies the pathogenesis of vascular disease, the role of the ERα in the vascular responses associated with acute systemic inflammation remains poorly characterized. Contractile and relaxation responses of isolated aortic segments were investigated 12 h after ip injection of saline or lipopolysaccharide (LPS, 10 mg/kg) in male wild-type (ERα +/+) and ERα-deficient (ERα-/-) mice. As previously observed, LPS-injected ERα+/+ mice displayed reduced contractile responses to phenylephrine and enhanced vasodilation in response to acetylcholine. In contrast, aortic tissues from LPS-injected ERα-/- mice displayed enhanced contractile responses and reduced sensitivity to acetylcholine- and sodium nitroprusside-induced vasodilation. LPS treatment in ERα+/+ and ERα -/- mice resulted in similar increased levels of systemic NO production and inducible NO synthase expression in the vascular wall. However, expression of mRNA and protein for endothelial NOS and soluble guanylate cyclase (α- and β-subunits) were significantly reduced in aortic tissues from LPS-treated ERα-/- animals, possibly accounting for reduced endothelial NO production and reduced smooth muscle responses to NO. These findings represent new evidence of the functional role of ERα in the male vasculature and suggest that during acute LPS-induced inflammatory responses, the ERα mediates the sustained expression of the molecular machinery essential for endothelial NO synthesis (i.e. endothelial NOS) and the vascular responses to NO (i.e. soluble guanylate cyclase).

Original languageEnglish (US)
Pages (from-to)1403-1411
Number of pages9
JournalEndocrinology
Volume148
Issue number3
DOIs
StatePublished - Mar 2007

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Estrogen Receptors
Lipopolysaccharides
Inflammation
Nitric Oxide
Blood Vessels
Vasodilation
Acetylcholine
Nitroprusside
Phenylephrine
Nitric Oxide Synthase Type II
Vascular Diseases
Smooth Muscle
Estrogens
Messenger RNA
Injections

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Compromised aortic vasoreactivity in male estrogen receptor-α- deficient mice during acute lipopolysaccharide-induced inflammation. / Corbacho, Ana M.; Eiserich, Jason P.; Zuniga, Luis A.; Valacchi, Giuseppe; Villablanca, Amparo C.

In: Endocrinology, Vol. 148, No. 3, 03.2007, p. 1403-1411.

Research output: Contribution to journalArticle

Corbacho, Ana M. ; Eiserich, Jason P. ; Zuniga, Luis A. ; Valacchi, Giuseppe ; Villablanca, Amparo C. / Compromised aortic vasoreactivity in male estrogen receptor-α- deficient mice during acute lipopolysaccharide-induced inflammation. In: Endocrinology. 2007 ; Vol. 148, No. 3. pp. 1403-1411.
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