冷应激下高血压大鼠收缩压和左室肥厚的干预

Intervention of systolic pressure and left ventricular hypertrophy in rats under cold stress

目的观察不同药物对冷应激下自发性高血压大鼠收缩压（SBP）、左心室肥厚（LVH）的影响。方法将40只10周龄雄性自发性高血压大鼠（160—200g）于（20±1）℃实验室适应性饲养7d，随机分成5组（n=8），即对照组、冷应激对照组、美托洛尔组、氨氯地平组、贝那普利组。每周测量1次大鼠SBP、体重和心率；放血处死后，称量大鼠左心室重量（LVW），计算其左心室重量指数（LVWI，mg／g）；放射免疫法测定血浆和心肌内皮素-1（ET-1）、血管紧张素Ⅱ（AngⅡ）浓度，化学法检测血浆和心肌NO浓度；用反转录聚合酶链式反应（RT—PCR）法检测组织中内皮素A受体mRNA表达。结果与冷应激对照组比较，各用药组大鼠SBP于第5周开始明显降低（P〈0．05）。与对照组[（2．89±0．19）mg／g]比较，冷应激对照组大鼠LVWI[（3．38±0．27）mg／g]明显增加（P〈0．05）；与冷应激对照组比较，氨氯地平组LVWI[（2．98±0．28）mg／g]明显降低（P〈0．05）。与对照组[（129．3±17．8）μmol／L]比较，冷应激对照组大鼠血浆NO浓度[（104．9±19．5）μmol／L]明显减少（P〈0．05）；与冷应激对照组比较，各用药组血液NO浓度为明显增高，差异均有统计学意义（P〈0．05）。与对照组[（4．5±1．9）pg／100mg]比较，冷应激对照组大鼠心肌ET-1[（6．3±1．5）pg／100mg]明显增加（P〈0．05）；与冷应激对照组比较，氨氯地平组ET-1[（4．4±1．0）pg／100mg]明显减少（P〈0．05）。冷应激对照组心肌内皮素A受体mRNA表达（0．86±0．23）明显高于对照组（0．45±0．16），差异有统计学意义（P〈0．01）；与冷应激对照组比较，氨氯地平组内皮素A受体mRNA表达（0．41±0．14）明显减少，差异有统计学意义（P〈0．01）。结论氨氯地平可以降低冷应激下自发性高血压大鼠的SBP升高，抑制LVH。

Objective To investigate the effects of different drugs on systolic blood pressure （SBP） and left ventricular hypertrophy （LVH） in spontaneously hypertensive rats under cold stress. Methods A total of 40 male spontaneously hypertensive rats aged 10 weeks （160-200 g） were given adaptive feeding for 7 days at a temperature of 20±1℃ and then randomly divided into control group, cold stress group, metoprolol group, amlodipine group, and benazepril group, with 8 rats in each group. SBP, body weight, and heart rate were measured once a week. After the rats were sacrificed by exsanguination, left ventricular weight （LVW） was measured, and left ventricular weight index （LVWI; mg/g） was calculated. Radioimmunoassay was used to measure the concentrations of endothelin-1 （ET-1） and angiotensin-Ⅱ （Ang-Ⅱ） in plasma and myocardium, and the chemical method was used to measure the concentrations of nitric oxide （NO） in plasma and myocardium. RT-PCR was used to measure the mRNA expression of endothelin-A receptor. Results Compared with the cold stress group, all medication groups showed significant reductions in SBP since week 5 （P〈0.05）. The cold stress group showed a significant increase in LVWI compared with the control group （3.38±0.27 mg/g vs 2.89±0.19 mg/g, P〈0.05）. The amlodipine group showed a significant reduction in LVWI compared with the cold stress group （2.98±0.28 mg/g vs 3.38±0.27 mg/g, P〈0.05）. The cold stress group showed a significant reduction in plasma NO concentration compared with the control group （104.9±19.5 μ mol/L vs 129.3±17.8 μ mol/L, P〈0.05）; compared with the cold stress group, all the medication groups showed significant increases in blood NO concentration （P〈0.05）. The cold stress group showed a significant increase in myocardial ET-1 concentration compared with the control group （6.3±1.5 pg/100 mg vs 4.5±1.9 pg/100 mg, P〈0.05） ; compared with the cold stressgmup, the amlodipine group showed a significant reduction in myocardial ET-1 concentration （4.4±l.0pg/100 mg vs 6.3 ±1.5 pg/100 mg, P〈0.05）. The cold stress group had significantly higher mRNA expression of endothelin-A receptor than the control group（0.86~0.23 vs 0.45±0.16, P〈0.01 ） ; compared with the cold stress group, the amlodipine group showed a significant reduction in the mRNA expression of endothelin-A receptor （0.41±0.14 vs 0.86±0.23, P〈0.01 ）. Coneluslon Amlodipine can reduce the increase in SBP and inhibit LVH in spontaneously hypertensive rats under cold stress.