Lindpaintner K, Sen S
Cleveland Clinic Foundation, Department of Cardiovascular Research, Ohio 44106.
J Hypertens. 1987 Dec;5(6):663-9. doi: 10.1097/00004872-198712000-00005.
Experimental and clinical evidence indicates that cardiac hypertrophy in systemic hypertension may not simply result from the mechanical stress of increased afterload. Several lines of evidence suggest that sympathetic nervous influence stimulates cardiac growth. A previous study indicated that sympathetic tone may be important in the two-kidney, one-clip model of renovascular hypertension. Hence, we investigated the role of cardiac beta-receptors by testing the effects of the cardioselective beta-receptor blocker, atenolol, on regression and prevention of ventricular hypertrophy in this model. Renal hypertensive rats were assigned to a 'prevention' and a 'reversal' protocol, receiving the drug before or after the development of hypertension and cardiac hypertrophy. Untreated control animals developed severe hypertension (205 +/- 9 mmHg) and marked cardiac hypertrophy (heart weight/body weight ratio: 3.86 +/- 0.23 mg/g) when compared to sham-operated controls (129 +/- 1 mmHg and 2.38 +/- 0.06 mg/g, respectively). Atenolol (440 mg/kg per day) failed to prevent or reverse hypertension (213 +/- 5 and 194 +/- 11 mmHg) or cardiac hypertrophy (4.10 +/- 0.39 and 3.51 +/- 0.25 mg/g, respectively). Effective beta-blockade was verified by significantly lower heart rates in treated animals (382 +/- 10 and 368 +/- 9 beats/min, respectively) than untreated controls (486 +/- 28 beats/min; P less than 0.01). Similarly, plasma renin activity returned to baseline in atenolol-treated animals. Cardiac catecholamines were markedly decreased in hypertrophied hearts (significant only for norepinephrine) and remained unaffected by atenolol treatment. However, both the prevention and reversal protocol strikingly reduced mortality in hypertensive animals (0 and 14%, respectively, versus 57%; P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
实验和临床证据表明，系统性高血压中的心脏肥大可能并非仅仅由后负荷增加的机械应力所致。多条证据表明，交感神经影响会刺激心脏生长。此前一项研究表明，交感神经张力在肾血管性高血压的两肾一夹模型中可能很重要。因此，我们通过测试心脏选择性β受体阻滞剂阿替洛尔对该模型中心室肥大消退和预防的作用，来研究心脏β受体的作用。将肾性高血压大鼠分为“预防”和“逆转”方案组，在高血压和心脏肥大发展之前或之后给予该药物。与假手术对照组（分别为129±1 mmHg和2.38±0.06 mg/g）相比，未经治疗的对照动物出现了严重高血压（205±9 mmHg）和明显的心脏肥大（心脏重量/体重比：3.86±0.23 mg/g）。阿替洛尔（每天440 mg/kg）未能预防或逆转高血压（分别为213±5和194±11 mmHg）或心脏肥大（分别为4.10±0.39和3.51±0.25 mg/g）。通过治疗动物的心率显著低于未治疗对照组（分别为382±10和368±9次/分钟，而未治疗对照组为486±28次/分钟；P<0.01），证实了有效的β受体阻滞。同样，阿替洛尔治疗的动物血浆肾素活性恢复到基线水平。心脏儿茶酚胺在肥大心脏中显著降低（仅去甲肾上腺素显著），且不受阿替洛尔治疗的影响。然而，预防和逆转方案均显著降低了高血压动物的死亡率（分别为0和14%，而对照组为57%；P<0.02）。（摘要截断于250字）
