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Selective cyclo‐oxygenase‐2 inhibition with celecoxib elevates blood pressure and promotes leukocyte adherence
Author(s) -
Muscará Marcelo N,
Vergnolle Nathalie,
Lovren Fina,
Triggle Christopher R,
Elliott Susan N,
Asfaha Samuel,
Wallace John L
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703232
Subject(s) - celecoxib , medicine , endocrinology , prostacyclin , blood pressure , creatinine , blood urea nitrogen , prostaglandin , plasma renin activity , captopril , cyclooxygenase , pharmacology , chemistry , renin–angiotensin system , enzyme , biochemistry
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. 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 mm Hg after 3 weeks). 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. 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. Superfusion of mesenteric venules with celecoxib (3 μ M ) in vivo resulted in significant increases in leukocyte adherence to the endothelium in both normal and hypertensive rats. These studies suggest that suppression of COX‐2 significantly influences vascular and/or renal function, leading to elevated blood pressure and leukocyte adherence.British Journal of Pharmacology (2000) 129 , 1423–1430; doi: 10.1038/sj.bjp.0703232