2004, English, Article edition: Effects of chronic PGHS-2 inhibition on PGHS-dependent vasoconstriction in the aged female rat Armstrong, Stephen J; Xu, Yi; Davidge, Sandra T

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  • text/​html
Published
  • Oxford University Press
  • 2004-02-01 00:00:00.0
Language
  • English

Edition details

Title
  • Effects of chronic PGHS-2 inhibition on PGHS-dependent vasoconstriction in the aged female rat
Author
  • Armstrong, Stephen J
  • Xu, Yi
  • Davidge, Sandra T
Published
  • Oxford University Press
  • 2004-02-01 00:00:00.0
Physical Description
  • text/​html
Subjects
Notes
  • Objective: In menopause, aging and decreased estrogen levels are risk factors contributing to impaired vascular function. Previously, in a young ovariectomized rat model, we demonstrated an increase in prostaglandin H synthase (PGHS)-dependent vasoconstriction that could be prevented by estrogen replacement. Subsequently, we found that, with aging, estrogen acts through suppression of the PGHS-2 isoform. Hypothesis: Chronic PGHS-2 inhibition reduces PGHS-dependent vasoconstriction in aging. Methods: Ovariectomized, aged (12 months) Sprague–Dawley rats were treated with a placebo ( n =​ 7), or the PGHS-2 inhibitor (NS-398, s.c. 3 mg/​kg) for 1 week ( n =​ 6) or 4 weeks ( n =​ 6). Methacholine (endothelium-dependent dilator) and phenylephrine (adrenergic constrictor) were used to assess vascular function in the absence or presence of the nonselective PGHS inhibitor, meclofenamate (1 µmol/​l) or the specific PGHS-2 inhibitor NS-398 (10 µmol/​l). Results: One week of chronic PGHS-2 inhibition abolished a PGHS-dependent shift in methacholine-induced relaxation, while modulation was still observed in phenylephrine constriction. Surprisingly, 4 weeks of PGHS-2 inhibition enhanced PGHS-dependent modulation of vasoconstriction ( P <0.05). PGH 2 /​thromboxane inhibition (U-51605, 50 µmol/​l) mimicked the results observed with PGHS inhibition among the groups. PGHS-2 expression increased with chronic PGHS-2 inhibition compared to control ( P <0.05). Conclusions: Our data indicate a paradoxical increase in PGHS-dependent vasoconstriction and PGHS-2 expression with prolonged inhibition of PGHS-2 activity. Hence, inhibitors of PGHS-2 activity may not be beneficial in counteracting the vascular dysfunction seen with aging and menopause.
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  • Copyright (C) 2004, European Society of Cardiology
Language
  • English
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