Selective cyclo-oxygenase-2 inhibition with celecoxib elevates blood pressure and promotes leukocyte adherence

Marcelo N. Muscará, Nathalie Vergnolle, Fina Lovren, Christopher Triggle, Susan N. Elliott, Samuel Asfaha, John L. Wallace

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

1. Selective inhibitors of cyclo-oxygenase-2 have been shown to be effective anti-inflammatory drugs with reduced gastrointestinal toxicity relative to conventional nonsteroidal anti-inflammatory drugs (NSAIDs). In the present study, we examined the possibility that selective COX-2 inhibition, by blocking prostacyclin synthesis, would increase blood pressure and cause leukocyte adherence and platelet aggregation. 2. Normal rats and rats with hypertension induced by chronic administration of N(ω)-nitro-L-arginine methylester were given celecoxib (10 mg kg -1) daily for 3 weeks. Celecoxib significantly elevated of blood pressure in both the normal and hypertensive rats (mean increase of > 33 mmHg after 3 weeks). 3. In normal rats, celecoxib had no effect on serum 6-keto prostaglandin (PG)F(1α) levels. Hypertensive rats exhibited a significant increase (82%) in serum 6-keto PGF(1α) levels, and this was reduced to the levels of normal rats by treatment with celecoxib. 4. Rats treated with celecoxib exhibited significant increases in weight gain (20%), plasma arginine-vasopressin levels (148%) and plasma urea (69%) relative to vehicle-treated controls. Plasma creatinine levels were unaffected by treatment with celecoxib, while plasma renin levels were significantly decreased (30%) relative to controls. 5. Superfusion of mesenteric venules with celecoxib (3 μM) in vivo resulted in significant increases in leukocyte adherence to the endothelium in both normal and hypertensive rats. 6. These studies suggest that suppression of COX-2 significantly influences vascular and/or renal function, leading to elevated blood pressure and leukocyte adherence.

Original languageEnglish
Pages (from-to)1423-1430
Number of pages8
JournalBritish Journal of Pharmacology
Volume129
Issue number7
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Celecoxib
Prostaglandin-Endoperoxide Synthases
Leukocytes
Blood Pressure
Prostaglandins F
Anti-Inflammatory Agents
Cyclooxygenase Inhibitors
Venules
Arginine Vasopressin
Epoprostenol
Serum
Platelet Aggregation
Renin
Pharmaceutical Preparations
Weight Gain
Endothelium

Keywords

  • Cyclo-oxygenase-2
  • Endothelium
  • Hypertension
  • Neutrophil adherence
  • Prostacyclin
  • Renal function

ASJC Scopus subject areas

  • Pharmacology

Cite this

Muscará, M. N., Vergnolle, N., Lovren, F., Triggle, C., Elliott, S. N., Asfaha, S., & Wallace, J. L. (2000). Selective cyclo-oxygenase-2 inhibition with celecoxib elevates blood pressure and promotes leukocyte adherence. British Journal of Pharmacology, 129(7), 1423-1430.

Selective cyclo-oxygenase-2 inhibition with celecoxib elevates blood pressure and promotes leukocyte adherence. / Muscará, Marcelo N.; Vergnolle, Nathalie; Lovren, Fina; Triggle, Christopher; Elliott, Susan N.; Asfaha, Samuel; Wallace, John L.

In: British Journal of Pharmacology, Vol. 129, No. 7, 2000, p. 1423-1430.

Research output: Contribution to journalArticle

Muscará, MN, Vergnolle, N, Lovren, F, Triggle, C, Elliott, SN, Asfaha, S & Wallace, JL 2000, 'Selective cyclo-oxygenase-2 inhibition with celecoxib elevates blood pressure and promotes leukocyte adherence', British Journal of Pharmacology, vol. 129, no. 7, pp. 1423-1430.
Muscará, Marcelo N. ; Vergnolle, Nathalie ; Lovren, Fina ; Triggle, Christopher ; Elliott, Susan N. ; Asfaha, Samuel ; Wallace, John L. / Selective cyclo-oxygenase-2 inhibition with celecoxib elevates blood pressure and promotes leukocyte adherence. In: British Journal of Pharmacology. 2000 ; Vol. 129, No. 7. pp. 1423-1430.
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