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塞来昔布与糖皮质激素合用时对血压和血浆氧化/抗氧化状态的影响。

The effect of celecoxib on blood pressure and plasma oxidant/antioxidant status in co-administration with glucocorticoid in rat.

机构信息

Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Biomed Pharmacother. 2018 Dec;108:1804-1808. doi: 10.1016/j.biopha.2018.10.047. Epub 2018 Oct 17.

Abstract

There is limited information about the concomitant uses of selective COX-2 inhibitors with corticosteroids or with antihypertensive medications. The aim of this study was to investigate the effect of celecoxib on blood pressure and plasma oxidant/antioxidant status in glucocorticoid-induced hypertension and in co-administration with captopril. Male Wistar rats received dexamethasone (30 μg/kg/day, s.c.) for 14 days. The tested groups received dexamethasone and orally treated with celecoxib (10, 25 or 50 mg/kg) or captopril (10, 20 or 40 mg/kg) or celecoxib (50 mg/kg) + captopril from day 8 to 14. Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were measured using tail-cuff method. Hydroperoxides concentration and ferric reducing antioxidant power (FRAP) value were determined in plasma samples. Dexamethasone significantly increased BP and plasma hydroperoxides level and decreased body weights. High dose of celecoxib resulted in a small but significant increase in SBP, DBP and MAP in normotensive rats however it did not alter BP markers in dexamethasone-induced hypertensive rats. Celecoxib reduced the hypotensive effect of all doses of captopril in dexamethasone-induced hypertensive rats however the SBP and MAP was preserved near to normal at low and middle doses of captopril but DBP was more than normal at low dose of captopril. Heart rate was not significantly altered by different treatments. High dose of celecoxib also increased plasma hydroperoxides concentration without effect on FRAP level. In conclusion, celecoxib did not change blood pressure in glucocorticoid-induced hypertensive rats but may blunt the hypotensive effect of low dose of captopril. Further studies are needed for detailed information addressing the effects of COX-2 inhibitors on blood pressure in concomitant uses with corticosteroids.

摘要

关于选择性 COX-2 抑制剂与皮质类固醇或与抗高血压药物同时使用的信息有限。本研究的目的是研究塞来昔布对糖皮质激素诱导性高血压以及与卡托普利同时使用时血压和血浆氧化/抗氧化状态的影响。雄性 Wistar 大鼠每天接受地塞米松(30μg/kg,sc)治疗 14 天。实验组接受地塞米松治疗,并口服塞来昔布(10、25 或 50mg/kg)或卡托普利(10、20 或 40mg/kg)或塞来昔布(50mg/kg)+卡托普利从第 8 天到第 14 天。使用尾套法测量心率、收缩压(SBP)、舒张压(DBP)和平均动脉压(MAP)。在血浆样本中测定羟自由基浓度和铁还原抗氧化能力(FRAP)值。地塞米松显著升高 BP 和血浆羟自由基水平并降低体重。高剂量塞来昔布在正常血压大鼠中导致 SBP、DBP 和 MAP 略有但显著增加,但在地塞米松诱导的高血压大鼠中未改变 BP 标志物。塞来昔布降低了地塞米松诱导的高血压大鼠中所有剂量卡托普利的降压作用,但在低剂量和中剂量卡托普利时,SBP 和 MAP 保持在接近正常水平,但在低剂量卡托普利时 DBP 高于正常。不同治疗方法对心率无显著影响。高剂量塞来昔布还增加了血浆羟自由基浓度,但对 FRAP 水平没有影响。总之,塞来昔布未改变地塞米松诱导的高血压大鼠的血压,但可能减弱卡托普利的低剂量降压作用。需要进一步研究以详细了解 COX-2 抑制剂与皮质类固醇同时使用对血压的影响。

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