Vaile J C, Chowdhary S, Osman F, Ross H F, Fletcher J, Littler W A, Coote J H, Townend J N
Department of Cardiovascular Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK.
Clin Sci (Lond). 2001 Dec;101(6):559-66.
The objective of the present study was to determine the autonomic effects of angiotensin II (AT(1)) receptor blocker therapy in heart failure. In a randomized double-blind cross-over study, we compared the effects of candesartan and placebo on baroreflex sensitivity and on heart rate variability at rest, during stress and during 24 h monitoring. Acute effects were assessed 4 h after oral candesartan (8 mg) and chronic effects after 4 weeks of treatment (dose titrated to 16 mg daily). The study group comprised 21 patients with heart failure [mean (S.E.M.) ejection fraction 33% (1%)], in the absence of angiotensin-converting enzyme (ACE) inhibitor therapy. We found that acute candesartan was not different from placebo in its effects on blood pressure or mean RR interval. Chronic candesartan significantly reduced blood pressure [placebo, 137 (3)/82 (3) mmHg; candesartan, 121 (4)/75 (2) mmHg; P<0.001; values are mean (S.E.M.)], but had no effect on mean RR interval [placebo, 857 (25) ms; candesartan, 857 (21) ms]. Compared with placebo there were no significant effects of acute or chronic candesartan on heart rate variability in the time domain and no consistent effects in the frequency domain. Baroreflex sensitivity assessed by the phenylephrine bolus method was significantly increased after chronic candesartan [placebo, 3.5 (0.5) ms/mmHg; candesartan, 4.8 (0.7) ms/mmHg; P<0.05], although there were no changes in cross-spectral baroreflex sensitivity. Thus, in contrast with previous results with ACE inhibitors, angiotensin II receptor blockade in heart failure did not increase heart rate variability, and there was no consistent effect on baroreflex sensitivity.
本研究的目的是确定血管紧张素II（AT(1)）受体阻滞剂治疗对心力衰竭患者自主神经的影响。在一项随机双盲交叉研究中，我们比较了坎地沙坦和安慰剂在静息、应激及24小时监测期间对压力反射敏感性和心率变异性的影响。口服坎地沙坦（8毫克）4小时后评估急性效应，治疗4周（剂量滴定至每日16毫克）后评估慢性效应。研究组包括21例心力衰竭患者[平均（标准误）射血分数33%（1%）]，且未接受血管紧张素转换酶（ACE）抑制剂治疗。我们发现，急性给予坎地沙坦对血压或平均RR间期的影响与安慰剂无差异。慢性给予坎地沙坦可显著降低血压[安慰剂组，137（3）/82（3）毫米汞柱；坎地沙坦组，121（4）/75（2）毫米汞柱；P<0.001；数值为平均（标准误）]，但对平均RR间期无影响[安慰剂组，857（25）毫秒；坎地沙坦组，857（21）毫秒]。与安慰剂相比，急性或慢性给予坎地沙坦对时域心率变异性均无显著影响，在频域也无一致影响。通过苯肾上腺素推注法评估的压力反射敏感性在慢性给予坎地沙坦后显著增加[安慰剂组，3.5（0.5）毫秒/毫米汞柱；坎地沙坦组，4.8（0.7）毫秒/毫米汞柱；P<0.05]，尽管交叉谱压力反射敏感性无变化。因此，与之前ACE抑制剂的结果相反，心力衰竭患者中血管紧张素II受体阻断并未增加心率变异性，对压力反射敏感性也无一致影响。
