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Related Experiment Videos

Aging increases PGHS-2-dependent vasoconstriction in rat mesenteric arteries.

K G Stewart1, Y Zhang, S T Davidge

  • 1Departments of Obstetrics/Gynecology and Physiology, Perinatal Research Centre, University of Alberta, Edmonton, Canada.

Hypertension (Dallas, Tex. : 1979)
|June 17, 2000
PubMed
Summary

Aging impairs blood vessel relaxation by increasing prostaglandin H synthase-2 (PGHS-2) activity, leading to vasoconstriction. Inhibiting PGHS-2 may restore vascular function in older individuals.

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Area of Science:

  • Cardiovascular physiology
  • Aging research
  • Endothelial function

Background:

  • The aging vascular endothelium exhibits functional and morphological changes.
  • Endothelium-derived eicosanoids are implicated in increased vascular tone during aging, but mechanisms remain unclear.

Purpose of the Study:

  • To investigate the roles of prostaglandin H synthase (PGHS) and nitric oxide in age-related changes in vascular function.
  • To test the hypothesis that aging increases PGHS-dependent vasoconstriction and decreases nitric oxide-dependent relaxation.

Main Methods:

  • Mesenteric arteries from young (3-month) and aged (12-month) female Sprague-Dawley rats were analyzed using a myograph system.
  • Vascular responses to methacholine were assessed with and without inhibitors of nitric oxide synthase, PGHS-1, PGHS-2, and the prostaglandin H2/thromboxane A2 receptor.

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Main Results:

  • Aging significantly blunted endothelium-dependent relaxation to methacholine.
  • Nitric oxide synthase inhibition affected relaxation in young but not aged rats.
  • PGHS-2 inhibition markedly enhanced methacholine-induced relaxation in aged rats, restoring function to young levels.
  • Arterial expression of PGHS-2 protein increased with age.

Conclusions:

  • Nitric oxide-dependent vascular modulation decreases with age.
  • Enhanced PGHS-2-mediated vasoconstriction contributes to impaired vascular function in aging.
  • PGHS-2 inhibition represents a potential therapeutic target for improving vascular health in aging.