Can celecoxib raise blood pressure and make white blood cells stick to blood vessel walls in rats?

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Selective inhibitors of cyclo-oxygenase-2 (COX-2) have been shown to be effective anti-inflammatory drugs with less gastrointestinal toxicity than conventional nonsteroidal anti-inflammatory drugs (NSAIDs). This study examined whether selective COX-2 inhibition, by blocking prostacyclin synthesis, would increase blood pressure and cause leukocyte adherence and platelet aggregation.

In controlled animal experiments, normal rats and rats with hypertension induced by chronic administration of Nomega-nitro-L-arginine methylester received celecoxib at 10 mg/kg daily for 3 weeks. Celecoxib significantly raised blood pressure in both normal and hypertensive rats, with a mean increase of more than 33 mm Hg after 3 weeks.

In normal rats, celecoxib had no effect on serum 6-keto prostaglandin (PG)F1α levels. Hypertensive rats had significantly increased serum 6-keto PGF1α levels, by 82%; celecoxib treatment reduced these levels to those of normal rats.

Compared with vehicle-treated controls, celecoxib-treated rats showed significant increases in weight gain (20%), plasma arginine-vasopressin levels (148%) and plasma urea (69%). Plasma creatinine levels were unaffected by celecoxib, while plasma renin levels were significantly lower, by 30%, than in controls.

In an in vivo experiment, superfusion of mesenteric venules—small veins in the tissue supporting the intestines—with celecoxib at 3 μM significantly increased leukocyte adherence to the endothelium, the inner lining of blood vessels, in both normal and hypertensive rats.

The studies suggest that suppressing COX-2 significantly influences vascular and/or renal function, leading to elevated blood pressure and leukocyte adherence.