Cyclooxygenase-2 inhibition restored endothelium-mediated relaxation in old obese Zucker rat mesenteric arteries

Emilie Vessières, Eric J. Belin de Chantemèle, Bertrand Toutain, Anne Laure Guihot, Alain Jardel, Laurent Loufrani, Daniel Henrion

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Metabolic syndrome is associated with reduced endothelial vasodilator function. It is also associated with the induction of cyclooxygenase-2 (COX2), which produces vasoactive prostanoids. The frequency of metabolic syndrome increases with age and aging per se is a risk factor associated with reduced endothelium-mediated relaxation. Nevertheless, the combined effect of aging and metabolic syndrome on the endothelium is less known. We hypothesized that COX2 derived prostanoids may affect endothelium function in metabolic syndrome associated with aging. We used obese Zucker rats, a model of metabolic syndrome. First order mesenteric arteries were isolated from 4- and 12-month-old rats and acetylcholine (endothelium)-dependent relaxation determined using wire-myography. Endothelium-mediated relaxation, impaired in young Zucker rats (89 versus 77% maximal relaxation; lean versus Zucker), was further reduced in old Zucker rats (72 versus 51%, lean versus Zucker). The effect of the nitric oxide-synthesis inhibitor L-NAME on the relaxation was reduced in both young and old Zucker rats without change in eNOS expression level. COX inhibition (indomethacin) improved acetylcholine-mediated relaxation in old obese rats only, suggesting involvement of vasoconstrictor prostanoids. In addition, COX2 inhibition (NS398) and TxA2/PGH2 receptor blockade (SQ29548) both improved relaxation in old Zucker rat arteries. Old Zucker rats had the highest TxB2 (TxA2 metabolite) blood level associated with increased COX2 immunostaining. Chronic COX2 blockade (Celecoxib, 3 weeks) restored endothelium-dependent relaxation in old Zucker rats to the level observed in old lean rats. Thus the combination of aging and metabolic syndrome further impairs endothelium-dependent relaxation by inducing an excessive production of COX2-derived vasoconstrictor(s); possibly TxA2.

Original languageEnglish (US)
Article number145
JournalFrontiers in Physiology
Volume1 NOV
DOIs
StatePublished - Dec 1 2010

Fingerprint

Zucker Rats
Mesenteric Arteries
Cyclooxygenase 2
Endothelium
Prostaglandins
Celecoxib
Vasoconstrictor Agents
Acetylcholine
Myography
Prostaglandin H2 Receptors Thromboxane A2
NG-Nitroarginine Methyl Ester
Vasodilator Agents
Indomethacin
Nitric Oxide
Arteries

Keywords

  • Aging
  • Cyclooxygenase-2
  • Endothelium
  • Metabolic syndrome
  • Resistance arteries
  • Vasodilatation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Cyclooxygenase-2 inhibition restored endothelium-mediated relaxation in old obese Zucker rat mesenteric arteries. / Vessières, Emilie; Belin de Chantemèle, Eric J.; Toutain, Bertrand; Guihot, Anne Laure; Jardel, Alain; Loufrani, Laurent; Henrion, Daniel.

In: Frontiers in Physiology, Vol. 1 NOV, 145, 01.12.2010.

Research output: Contribution to journalArticle

Vessières, Emilie ; Belin de Chantemèle, Eric J. ; Toutain, Bertrand ; Guihot, Anne Laure ; Jardel, Alain ; Loufrani, Laurent ; Henrion, Daniel. / Cyclooxygenase-2 inhibition restored endothelium-mediated relaxation in old obese Zucker rat mesenteric arteries. In: Frontiers in Physiology. 2010 ; Vol. 1 NOV.
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AU - Guihot, Anne Laure

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AU - Loufrani, Laurent

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