Frohlich E D, McLoughlin M, Ketelhut R
Department of Internal Medicine, Ochsner Clinic, New Orleans, Louisiana.
Am J Cardiol. 1992 Jan 15;69(3):229-32. doi: 10.1016/0002-9149(92)91310-z.
To determine the hemodynamic and certain metabolic effects of clentiazem, a diltiazem congener, 10 untreated essential hypertensive patients were given the calcium antagonist in 3 successive doses totaling 1.0 mg/kg intravenously. Mean arterial pressure and total peripheral resistance progressively declined from 121 +/- 3 mm Hg and 47 +/- 2 U (mean) to 110 +/- 3 mm Hg and 33 +/- 1 U, respectively (p less than 0.05); heart rate remained unchanged. Cardiac output increased as a result of augmented cardiopulmonary volume (p less than 0.05) produced by peripheral venoconstriction and norepinephrine release (from 258 +/- 41 to 319 +/- 42 pg/ml; p less than 0.01). Surprisingly, there was an immediate reduction in plasma aldosterone (10.4 +/- 1.2 to 6.5 +/- 1.0 ng/dl; p less than 0.01), serum potassium (4.3 +/- 0.1 to 3.6 +/- 0.1 mEq/dl; p less than 0.001) and calcium (9.5 +/- 0.1 to 8.8 +/- 0.1 mg/dl; p less than 0.001) concentrations, whereas epinephrine increased (21.2 +/- 3.3 to 45.8 +/- 5.9 pg/ml; p less than 0.002). Previous studies with diltiazem, conducted similarly, did not show these changes. Therefore, clentiazem reduced mean arterial pressure through a decrease in total peripheral resistance, and released epinephrine was associated with intracellular potassium influx (urinary potassium did not change). The inhibited aldosterone release was not compensated by altered renal blood flow, glomerular filtration or increased plasma renin activity. These findings underscore the concept that calcium antagonists are a remarkably heterogeneous antihypertensive group.
为了确定地尔硫䓬同类物克仑硫䓬的血流动力学及某些代谢效应，对10例未经治疗的原发性高血压患者静脉连续给予3次钙剂拮抗剂，总量为1.0mg/kg。平均动脉压和总外周阻力分别从121±3mmHg和47±2U（平均值）逐渐降至110±3mmHg和33±1U（p<0.05）；心率保持不变。由于外周静脉收缩和去甲肾上腺素释放导致心肺容量增加（p<0.05），心输出量增加（从258±41增至319±42pg/ml；p<0.01）。令人惊讶的是，血浆醛固酮（从10.4±1.2降至6.5±1.0ng/dl；p<0.01）、血清钾（从4.3±0.1降至3.6±0.1mEq/dl；p<0.001）和钙（从9.5±0.1降至8.8±0.1mg/dl；p<0.001）浓度立即降低，而肾上腺素增加（从21.2±3.3增至45.8±5.9pg/ml；p<0.002）。以前以类似方式进行的地尔硫䓬研究未显示这些变化。因此，克仑硫䓬通过降低总外周阻力降低平均动脉压，释放的肾上腺素与细胞内钾内流有关（尿钾未改变）。醛固酮释放受抑制未因肾血流量改变、肾小球滤过或血浆肾素活性增加而得到代偿。这些发现强调了钙拮抗剂是一个显著异质性的抗高血压药物组这一概念。
