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Selective cyclooxygenase-2 inhibition with etoricoxib elevates blood pressure and alters vascular reactivity
Critical Care volume 7, Article number: P121 (2003)
Selective inhibitors of cyclooxygenase-2 (COX-2) have been shown to be effective anti-inflammatory drugs with reduced gastrointestinal toxicity relative to conventional nonsteroidal anti-inflammatory drugs. However, given the ability of selective COX-2 inhibitors to suppress vascular prostacyclin synthesis, apart from their deleterious action on renal function, we decided to test the effects of the novel COX-2 inhibitor etoricoxib (ETO) on blood pressure (BP) and vascular reactivity.
Normotensive male Wistar rats and spontaneously hypertensive rats (SHRs) received ETO (10 mg/kg, p.o.) once daily for 5 weeks. BP measurements were performed weekly by the tail-cuff method, and at the end of the treatment period the animals had their aortae removed in order to test the in vitro responses to both acetylcholine and sodium nitroprusside.
ETO had no effect on the BP levels of normotensive Wistar rats. However, significant elevation of BP was observed in ETO-treated SHRs in comparison with the untreated SHRs (third week, 204.2 ± 5.8 vs 175.8 ± 5.5 mmHg, P < 0.001; fourth week, 206.4 ± 8.9 vs 185.0 ± 3.8 mmHg, P < 0.05; fifth week, 237.4 ± 4.9 vs 209.8 ± 4.0 mmHg, P < 0.001). Norepinephrine-precontracted aorta rings obtained from ETO-treated SHRs also showed a decreased relaxation response to both acetylcholine and sodium nitroprusside in vitro in comparison with the untreated SHR group. No ETO-related effects were observed in the in vitro reactivity of aorta rings obtained from the normotensive animals.
These preliminary results suggest that the selective COX-2 inhibitor ETO significantly impairs vascular relaxation in SHRs, thus contributing, at least in part, to the significant potentiation of the hypertensive status of these animals.
Financial support from FAPESP, CAPES, and CNPq – PRONEX.
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Fernandes, L., Martinez, L., Teixeira, S. et al. Selective cyclooxygenase-2 inhibition with etoricoxib elevates blood pressure and alters vascular reactivity. Crit Care 7, P121 (2003). https://doi.org/10.1186/cc2317
- Sodium Nitroprusside
- Blood Pressure Level
- Aorta Ring
- Vascular Reactivity