Cyclooxygenase-2 blockade does not impair endothelial vasodilator function in healthy volunteers

Randomized evaluation of rofecoxib versus naproxen on endothelium-dependent vasodilatation

Subodh Verma, Satish R. Raj, Lana Shewchuk, Kieren Mather, Todd J. Anderson

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Background - From a cardiovascular standpoint, the safety of cyclooxygenase-2 (COX-2) blockers has been a topic of increasing concern. This concern stemmed from observations indicating that the COX-2 isoform is the major source of endothelium-derived prostacyclin and, hence, that selective blockade of this enzyme may impair endothelial health. To investigate this matter, we examined the effects of 7 days of treatment with rofecoxib versus naproxen on endothelial function in healthy volunteers. Methods and Results - Thirty-five healthy volunteers were randomized to receive 7-day treatment with either rofecoxib (25 mg/d, n = 18) or naproxen (750 mg/d, n = 17). Vascular response measurements were conducted using forearm strain-gauge plethysmography. Changes in forearm blood flow in response to the endothelium-dependent vasodilator acetylcholine (3, 10, and 30 μg/min) and the endothelium-independent vasodilator sodium nitroprusside (1 and 10 μg/min) were assessed before and after treatment. Acetylcholine evoked a dose-dependent increase in forearm blood flow in all groups. Importantly, treatment resulted in no change in acetylcholine-mediated increases in forearm blood flow in either group (naproxen, P = 0.27; rofecoxib, P = 0.58). Similarly, there was no change in forearm blood flow in response to sodium nitroprusside (naproxen, P = 0.55; rofecoxib, P = 0.63). Conclusions - We herein describe, for the first time, the effects of COX-2-selective inhibition on endothelium-dependent vasodilatation in healthy adults. COX-2 blockade, when used at the doses employed therapeutically (which are known to inhibit vascular prostacyclin production) did not result in significant changes in endothelial vasodilator responses in healthy volunteers. The effects of COX-2 inhibitors on vasodilator responses in patients with coronary artery disease remain to be determined.

Original languageEnglish (US)
Pages (from-to)2879-2882
Number of pages4
JournalCirculation
Volume104
Issue number24
StatePublished - Dec 11 2001
Externally publishedYes

Fingerprint

Naproxen
Cyclooxygenase 2
Vasodilator Agents
Forearm
Vasodilation
Endothelium
Healthy Volunteers
Acetylcholine
Nitroprusside
Epoprostenol
Blood Vessels
Endothelium-Dependent Relaxing Factors
Plethysmography
Cyclooxygenase 2 Inhibitors
Therapeutics
Coronary Artery Disease
Protein Isoforms
rofecoxib
Safety
Health

Keywords

  • Endothelium-derived factors
  • Patients
  • Prostaglandins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Cyclooxygenase-2 blockade does not impair endothelial vasodilator function in healthy volunteers : Randomized evaluation of rofecoxib versus naproxen on endothelium-dependent vasodilatation. / Verma, Subodh; Raj, Satish R.; Shewchuk, Lana; Mather, Kieren; Anderson, Todd J.

In: Circulation, Vol. 104, No. 24, 11.12.2001, p. 2879-2882.

Research output: Contribution to journalArticle

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AU - Raj, Satish R.

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AU - Mather, Kieren

AU - Anderson, Todd J.

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