Division of Cardiology, Department of Medicine, Faculty of Medicine, Kindai University, Osaka 589-8511, Japan; Department of Rehabilitation Medicine, Kindai University, Osaka 589-8511, Japan.
Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
Int J Cardiol. 2019 Jun 15;285:65-71. doi: 10.1016/j.ijcard.2019.02.062. Epub 2019 Mar 4.
To compare the effects of metoprolol and carvedilol on baroreflex-mediated sympathetic circulatory regulation.
In anesthetized Wistar-Kyoto rats, carotid sinus baroreceptor regions were isolated. Changes in sympathetic nerve activity (SNA), arterial pressure (AP), heart rate (HR), and aortic flow (AoF) in response to a staircase-wise pressure input were examined before (control) and after intravenous injection of low-dose metoprolol (2 mg/kg), high-dose metoprolol (10 mg/kg), or carvedilol (0.67 mg/kg) (n = 6 each). Peripheral vascular resistance (PVR) was calculated from mean AP divided by mean AoF.
Low-dose metoprolol had limited effect on sympathetic AP regulation compared to control [operating-point AP (drug vs. control): 88.7 ± 7.1 vs. 98.3 ± 3.3 mm Hg, not significant] despite a significant bradycardic effect. Although high-dose metoprolol showed central sympathoinhibition, it increased PVR at a given SNA as a peripheral effect. Consequently, high-dose metoprolol decreased the operating-point AP slightly (96.1 ± 2.7 vs. 101.9 ± 2.7 mm Hg, P < 0.01). Carvedilol showed no significant central sympathoinhibition at the dose examined in this study, but significantly reduced PVR at a given SNA, leading to a marked reduction in the operating-point AP (71.9 ± 8.2 vs. 112.6 ± 7.6 mm Hg, P < 0.05).
Low-dose metoprolol has limited hypotensive effect despite blockade of sympathetic HR regulation. Although high-dose metoprolol induces central sympathoinhibition, it also induces peripheral vasoconstriction that antagonizes the hypotensive effect. In contrast, carvedilol exhibits hypotensive effect mainly through peripheral vasodilation. Although carvedilol is frequently classified as a β-blocker, its vasodilatory effect via α-adrenergic blockade plays an important role in AP reduction or heart failure treatment.
比较美托洛尔和卡维地洛对压力感受性反射介导的交感循环调节的影响。
在麻醉的 Wistar-Kyoto 大鼠中，分离出颈动脉窦压力感受器区域。在静脉注射低剂量美托洛尔（2mg/kg）、高剂量美托洛尔（10mg/kg）或卡维地洛（0.67mg/kg）之前（对照）和之后，检查交感神经活性（SNA）、动脉压（AP）、心率（HR）和主动脉流量（AoF）对阶梯式压力输入的变化（n=6 只）。外周血管阻力（PVR）由平均 AP 除以平均 AoF 计算得出。
与对照相比，低剂量美托洛尔对交感 AP 调节的作用有限[作用点 AP（药物与对照）：88.7±7.1 与 98.3±3.3mmHg，无显著性]，尽管有明显的心动过缓作用。虽然高剂量美托洛尔显示出中枢性交感神经抑制作用，但它作为外周作用增加了给定 SNA 时的 PVR。因此，高剂量美托洛尔略微降低了作用点 AP（96.1±2.7 与 101.9±2.7mmHg，P<0.01）。在本研究中检查的剂量下，卡维地洛没有显示出明显的中枢性交感神经抑制作用，但显著降低了给定 SNA 时的 PVR，导致作用点 AP 明显降低（71.9±8.2 与 112.6±7.6mmHg，P<0.05）。
尽管阻断了交感 HR 调节，但低剂量美托洛尔的降压作用有限。虽然高剂量美托洛尔诱导中枢性交感神经抑制，但它也诱导外周血管收缩，拮抗降压作用。相比之下，卡维地洛主要通过外周血管扩张发挥降压作用。虽然卡维地洛常被归类为β受体阻滞剂，但它通过α肾上腺素能阻滞的血管扩张作用在降低血压或治疗心力衰竭方面发挥着重要作用。
