Parecoxib Increases Blood Pressure Through Inhibition of Cyclooxygenase-2 Messenger RNA in an Experimental Model.

Background: Cyclooxygenase-2 selective inhibitors have been developed to alleviate pain and inflammation; however, the use of a selective cyclooxygenase-2 inhibitor is associated with mild edema, hypertension, and cardiovascular risk.
Aim: To evaluate, in an experimental model in normotensive rats, the effect of treatment with parecoxib in comparison with diclofenac and aspirin and L-NAME, a non-selective nitric oxide synthetase, on mean arterial blood pressure, and cyclooxygenase-1 and -2 messenger RNA and protein expression in aortic tissue.
Methods: Rats were treated for seven days with parecoxib (10 mg/kg/day), diclofenac (3.2 mg/kg/day), aspirin (10 mg/kg/day), or L-NAME (10 mg/kg/day). Mean arterial blood pressure was evaluated in rat tail; cyclooxygenase-1 and -2 were evaluated by reverse transcription-polymerase chain reaction and Western blot analysis in aortic tissue.
Results: Parecoxib and L-NAME, but not aspirin and diclofenac, increased mean arterial blood pressure by about 50% (p < 0.05) without changes in cardiac frequency. Messenger RNA cyclooxygenase-1 expression in aortic tissue was not modified with any drug (p < 0.05). L-NAME and parecoxib treatment decreased messenger RNA cyclooxygenase-2 and cyclooxygenase-2 (p < 0.05). While cyclooxygenase-1 protein decreased with the three drugs tested but not with L-NAME (p < 0.05), the cyclooxygenase-2 protein decreased only with aspirin and parecoxib (p < 0.05).
Conclusion: Parecoxib increases the blood pressure of normotensive rats by the suppression of COX-2 gene expression, which apparently induced cardiovascular control.