Acute effects of intravenous carvedilol versus metoprolol on baroreflex-mediated sympathetic circulatory regulation in rats
Acute effects of intravenous carvedilol versus metoprolol on baroreflex-mediated sympathetic circulatory regulation in rats
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静脉注射卡维地洛与美托洛尔对大鼠压力感受反射介导的交感循环调节的急性影响
DOI：
10.1016/j.ijcard.2019.02.062
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发表时间：
2019
影响因子：
3.5
通讯作者：
Sugimachi Masaru
中科院分区：
文献类型：
--
作者：
Yamamoto Hiromi;Kawada Toru;Shimizu Shuji;Hayama Yohsuke;Shishido Toshiaki;Iwanaga Yoshitaka;Fukuda Kanji;Miyazaki Shunichi;Sugimachi Masaru
目的比较美托洛尔和卡维地洛对压力反射介导的交感循环调节的影响。方法在麻醉的Wistar-Kyoto大鼠中，分离颈动脉窦压力感受器区。在静脉注射低剂量美托洛尔（2 mg/kg）、高剂量美托洛尔（10 mg/kg）或卡维地洛（0.67 mg/kg）（每组n= 6）之前（对照组）和之后，检查交感神经活动（SNA）、动脉压（AP）、心率（HR）和主动脉血流（AoF）对阶梯式压力输入的反应变化。外周血管阻力（PVR）计算平均AP除以平均AoF. ResultsLow剂量美托洛尔交感神经AP调节的影响有限，与对照组相比[操作点AP（药物与对照）：88.7 ± 7.1与98.3 ± 3.3毫米汞柱，不显着]，尽管有显着的心动过缓的效果。虽然大剂量美托洛尔显示中枢交感神经抑制，但其外周效应增加了给定SNA的PVR。因此，大剂量美托洛尔使工作点AP略有下降（96.1 ± 2.7 vs.101.9 ± 2.7 mm Hg，P< 0.01）。卡维地洛对中枢交感神经系统无明显抑制作用，但能显著降低SNA时的PVR，使工作点AP显著降低（71.9 ± 8.2vs.112.6 ± 7.6mmHg，P< 0.05）。虽然大剂量美托洛尔引起中枢交感神经抑制，但它也引起外周血管收缩，从而拮抗这种抑制作用。卡维地洛主要通过扩张外周血管发挥舒张作用。虽然卡维地洛通常被归类为β受体阻滞剂，但其通过α1肾上腺素能阻滞的血管舒张作用在AP减少或心力衰竭治疗中起着重要作用。
AimsTo compare the effects of metoprolol and carvedilol on baroreflex-mediated sympathetic circulatory regulation.MethodsIn 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.ResultsLow-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).ConclusionLow-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 α1-adrenergic blockade plays an important role in AP reduction or heart failure treatment.