Chulalongkorn Medical Journal


Background : Treatment with selective cyclooxygenase-2 (COX-2) inhibitor is associatedwith increased risk of cardiovascular events. Inhibition of COX-2 reducesvascular prostacyclin synthesis without disrupting COX-1-derivedthromboxane synthesis, which may alter vascular tone andresponsiveness.Objective : To examine the effects of two COX-2 inhibitors, meloxicam and etoricoxib,on blood pressure and vascular reactivity in rats.Methods : Unconscious blood pressure was obtained from Sprague Dawley ratsby a tail-cuff method, and then the rats were divided into 3 groups(n = 9 in all groups): 1) non–treated control, 2) meloxicam 1 mg/kg/d, 3)etoricoxib 3 mg/kg/d. Drugs were orally administered 4 times/week in aconsecutive day for 6 weeks. At the end of the treatments, unconsciousblood pressure and pulse wave velocity (PWV, an index of arterialcompliance) were determined. Thoracic aorta was isolated for theassessment of vascular responses to phenylephrine (PE, α-adrenoceptoragonist; 10-10–10-6 M), isoproterenol (Iso, β-adrenoceptor agonist;10-8–10-4 M), and acetylcholine (Ach, muscarinic receptor agonist;10-9–10-5 M).Results : Etoricoxib caused a more pronounced effect on body weight gain thanmeloxicam, suggesting its greater effect on body fluid. Both COX-2inhibitors did not alter PWV, indicating no change in arterial compliance.The systolic pressure, diastolic pressure and mean arterial pressure ofetoricoxib group, but not meloxicam group, showed non-significantlyhigher than those of control group. The responsiveness of aortic ringsto PE and Ach were not altered by either meloxicam or etoricoxibtreatment. However, both drug treatments caused a significantly greatervasorelaxation responses to Iso (P <0.05).Conclusions : These results show that etoricoxib, but not meloxicam, has a nonsignificantincreasing blood pressure which may be associated withbody fluid retention. Both COX-2 inhibitors enhance β-adrenoceptorvasodilation.


Faculty of Medicine, Chulalongkorn University

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