新型血管紧张素转换酶抑制剂阿拉普利对充血性心力衰竭患者神经激素因子变化及动脉压力反射敏感性的影响

Effects of a new angiotensin-converting enzyme inhibitor, alacepril, on changes in neurohormonal factors and arterial baroreflex sensitivity in patients with congestive heart failure.

作者信息

Kinugawa T, Kato M, Mori M, Endo A, Kato T, Hamada T, Noguchi N, Omodani H, Osaki S, Ogino K, Miyakoda H, Hisatome I, Shigemasa C

机构信息

The 1st Department of Internal Medicine, Tottori University, Yonago, Japan.

出版信息

Eur J Clin Pharmacol. 1998 May;54(3):209-14. doi: 10.1007/s002280050447.

DOI:10.1007/s002280050447

PMID:9681661

Abstract

OBJECTIVE

Patients with heart failure have abnormal neurohormonal regulation during orthostatic stress, and abnormal arterial baroreflex function. This study investigated the effects of alacepril, a new angiotensin-converting enzyme inhibitor with sulfhydryls, on changes in neurohormonal factors during tilt and on the arterial baroreflex control of heart rate.

METHODS

Plasma concentrations of noradrenaline, adrenaline, renin activity, angiotensin II, and atrial natriuretic peptide were measured at supine rest and after 30 degrees head-up tilt with measurements of central venous pressure and cardiac dimensions in seven patients with congestive heart failure (65 years, ejection fraction = 34%). Arterial baroreflex control of heart rate was assessed by phenylephrine bolus. The arterial baroreflex test was re-examined 3 h after oral alacepril (37.5 mg). The tilt and arterial baroreflex tests were repeated 12 weeks after alacepril treatment (50 mg x day(-1)).

RESULTS

Heart rate, blood pressure, and neurohormonal factors did not differ before and after chronic alacepril, except for a trend toward an increase in renin activity (2.0 vs 4.9 ng x ml(-1) x h(-1)). Head-up tilt decreased central venous pressure (-2.5 mmHg) with a decrease in cardiac dimensions in the pre-alacepril phase. These changes were accompanied by increases in noradrenaline, adrenaline, and angiotensin II and a decrease in atrial natriuretic peptide. After chronic alacepril, the increase in noradrenaline during head-up tilt tended to be smaller (84 vs 30 pg x ml(-1)), with similar changes in central venous pressure (-3.4 mmHg) and cardiac dimensions. Both acute (3.6 vs 4.8 ms mmHg(-1)) and chronic (3.6 vs 6.7 ms mmHg(-1)) alacepril treatment was associated with a trend towards an increase in the arterial baroreflex control of heart rate.

CONCLUSION

These results suggest that treatment with alacepril may cause a reduction of sympathetic activation during orthostatic stress and may enhance arterial baroreflex function in patients with mild to moderate heart failure.

摘要

目的

心力衰竭患者在体位性应激期间存在神经激素调节异常以及动脉压力反射功能异常。本研究调查了一种新型含巯基的血管紧张素转换酶抑制剂阿拉普利对倾斜期间神经激素因子变化以及心率的动脉压力反射控制的影响。

方法

在7例充血性心力衰竭患者（65岁，射血分数 = 34%）仰卧休息时及头高位倾斜30度后，测量去甲肾上腺素、肾上腺素、肾素活性、血管紧张素II和心房利钠肽的血浆浓度，并测量中心静脉压和心脏大小。通过静脉推注去氧肾上腺素评估心率的动脉压力反射控制。口服阿拉普利（37.5 mg）3小时后重新进行动脉压力反射测试。阿拉普利治疗（50 mg×日⁻¹）12周后重复倾斜和动脉压力反射测试。

结果

除肾素活性有升高趋势（2.0对4.9 ng×ml⁻¹×h⁻¹）外，慢性阿拉普利治疗前后心率、血压和神经激素因子无差异。在服用阿拉普利前阶段，头高位倾斜使中心静脉压降低（-2.5 mmHg），心脏大小减小。这些变化伴随着去甲肾上腺素、肾上腺素和血管紧张素II的增加以及心房利钠肽的减少。慢性阿拉普利治疗后，头高位倾斜期间去甲肾上腺素的增加趋势较小（84对30 pg×ml⁻¹），中心静脉压（-3.4 mmHg）和心脏大小有类似变化。急性（3.6对4.8 ms mmHg⁻¹）和慢性（3.6对6.7 ms mmHg⁻¹）阿拉普利治疗均与心率的动脉压力反射控制有增加趋势相关。