Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University.
Department of Pharmacy, Toho University Sakura Medical Center.
Biol Pharm Bull. 2023;46(9):1324-1331. doi: 10.1248/bpb.b23-00391.
Ca channel blockers have potent vasodilatory effects and excellent efficacy in preserving organ blood flow. These hemodynamic actions may be partly controlled by the functional stiffness of conduit arteries. In this study, we assessed the effects of the L-type Ca channel blocker nifedipine on aortic and femoral arterial stiffness (referred to as aortic β and femoral β, respectively) in anesthetized rabbits. To further clarify the involvement of the autonomic nervous system, we compared the effects of nifedipine with those of the L/N-type Ca channel blocker cilnidipine. Further, the effect of the α-adrenergic receptor blocker doxazosin on the effects of nifedipine on arterial elasticity was examined. An antihypertensive dose of nifedipine (300 µg/kg, administered intravenously) was found to increase the aortic β but hardly affected the femoral β. An antihypertensive dose of cilnidipine (30 µg/kg, administered intravenously) increased the aortic β but decreased the femoral β. Interestingly, nifedipine decreased the femoral β in the presence of the α-adrenoceptor blocker doxazosin (1 mg/kg, administered intravenously). These effects suggest that L-type Ca channel blockers essentially increase vascular elasticity via the decrement in arterial stiffness in the femoral artery segment, which is modified by the presence or absence of the inhibitory effect of each drug on reflex sympathetic nerve activity, while decreasing vascular elasticity via the increment in arterial stiffness in the aortic segment independently of sympathetic nerve activity.
钙通道阻滞剂具有强大的血管扩张作用,并能有效地保持器官血流。这些血液动力学作用可能部分受到导血管功能硬度的控制。在这项研究中,我们评估了 L 型钙通道阻滞剂硝苯地平对麻醉兔主动脉和股动脉僵硬(分别称为主动脉β和股β)的影响。为了进一步阐明自主神经系统的参与,我们比较了硝苯地平与 L/N 型钙通道阻滞剂西尼地平的作用。此外,还研究了α-肾上腺素能受体阻滞剂多沙唑嗪对硝苯地平对动脉弹性影响的作用。发现抗高血压剂量的硝苯地平(300μg/kg,静脉注射)增加了主动脉β,但几乎不影响股β。抗高血压剂量的西尼地平(30μg/kg,静脉注射)增加了主动脉β,但降低了股β。有趣的是,在存在α-肾上腺素能受体阻滞剂多沙唑嗪(1mg/kg,静脉注射)的情况下,硝苯地平降低了股β。这些结果表明,L 型钙通道阻滞剂通过降低股动脉段的动脉僵硬来增加血管弹性,这是由每种药物对反射性交感神经活动的抑制作用的存在与否来调节的,而通过增加主动脉段的动脉僵硬来降低血管弹性,而不依赖于交感神经活动。