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

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-omega-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). 3 In normal rats, celecoxib had no effect on serum 6-keto prostaglandin (PG)F-1 alpha levels. Hypertensive rats exhibited a significant increase (82%) in serum 6-keto PGF(1 alpha) 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 mu M) 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.