Wang Yan, Evangelista Stefano, Liu Yu, Zhang Ming-Sheng
Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi Province, China.
J Int Med Res. 2013 Jun;41(3):603-17. doi: 10.1177/0300060513477576. Epub 2013 May 16.
This study examined the combined effect of nebivolol (NEB) and hydrochlorothiazide (HCTZ) on cardiovascular function in spontaneously hypertensive rats (SHR).
SHR normotensive male rats were randomly assigned to five groups (n = 8 per group): (i) SHR control group; (ii) NEB 2 mg/kg per day group; (iii) HCTZ 10 mg/kg per day group; (iv) NEB 2 mg/kg per day + HCTZ 10 mg/kg per day group; (v) Eight age-matched Wistar-Kyoto normotensive male rats served as the control group. All groups were treated orally for 8 weeks.
The combination of NEB + HCTZ synergistically reduced systolic blood pressure and heart rate compared with either monotherapy. HCTZ increased water intake, which is a sign of diuresis. NEB reduced plasma angiotensin II concentration, which was increased in SHR and after HCTZ treatment. NEB + HCTZ increased plasma nitric oxide (NO) concentration and NO synthase activity, which were both reduced in SHR. NEB + HCTZ normalized femoral arterial vasorelaxation induced by acetylcholine, which was impaired in SHR.
The combination of NEB + HCTZ provided a number of beneficial and additive effects due to the synergistic characteristics of both drugs, in an experimental rat model of hypertension.
本研究考察了奈必洛尔（NEB）与氢氯噻嗪（HCTZ）联合应用对自发性高血压大鼠（SHR）心血管功能的影响。
将SHR正常血压雄性大鼠随机分为五组（每组n = 8）：（i）SHR对照组；（ii）NEB 2毫克/千克/天组；（iii）HCTZ 10毫克/千克/天组；（iv）NEB 2毫克/千克/天+HCTZ 10毫克/千克/天组；（v）八只年龄匹配的Wistar-Kyoto正常血压雄性大鼠作为对照组。所有组均口服给药8周。
与单一疗法相比，NEB+HCTZ联合用药可协同降低收缩压和心率。HCTZ增加了水摄入量，这是利尿的一个迹象。NEB降低了血浆血管紧张素II浓度，该浓度在SHR中以及HCTZ治疗后均升高。NEB+HCTZ增加了血浆一氧化氮（NO）浓度和NO合酶活性，这两者在SHR中均降低。NEB+HCTZ使乙酰胆碱诱导的股动脉血管舒张恢复正常，而在SHR中该血管舒张受损。
在高血压实验大鼠模型中，由于两种药物的协同特性，NEB+HCTZ联合用药产生了许多有益的相加作用。
