Leloup Arthur, De Moudt Sofie, Van Hove Cor, Fransen Paul
Laboratory of Physiopharmacology, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
Laboratory of Pharmacology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Front Physiol. 2017 Oct 30;8:858. doi: 10.3389/fphys.2017.00858. eCollection 2017.
Large, elastic arteries buffer the pressure wave originating in the left ventricle and are constantly exposed to higher amplitudes of cyclic stretch (10%) than muscular arteries (2%). As a crucial factor for endothelial and smooth muscle cell function, cyclic stretch has, however, never been studied in aortic segments of mice. To investigate the effects of cyclic stretch on vaso-reactivity of mouse aortic segments, we used the Rodent Oscillatory Tension Set-up to study Arterial Compliance (ROTSAC). The aortic segments were clamped at frequencies of 6-600 bpm between two variable preloads, thereby mimicking dilation as upon left ventricular systole and recoiling as during diastole. The preloads corresponding to different transmural pressures were chosen to correspond to a low, normal or high amplitude of cyclic stretch. At different time intervals, cyclic stretch was interrupted, the segments were afterloaded and isometric contractions by α-adrenergic stimulation with 2 μM phenylephrine in the absence and presence of 300 μM L-NAME (eNOS inhibitor) and/or 35 μM diltiazem (blocker of voltage-gated Ca channels) were measured. As compared with static or cyclic stretch at low amplitude (<10 mN) or low frequency (0.1 Hz), cyclic stretch at physiological amplitude (>10 mN) and frequency (1-10 Hz) caused better conservation of basal NO release with time after mounting. The relaxation of PE-precontracted segments by addition of ACh to stimulate NO release was unaffected by cyclic stretch. In the absence of basal NO release (hence, presence of L-NAME), physiological in comparison with aberrant cyclic stretch decreased the baseline tension, attenuated the phasic contraction by phenylephrine in the absence of extracellular Ca and shifted the smaller tonic contraction more from a voltage-gated Ca channel-mediated to a non-selective cation channel-mediated. Data highlight the need of sufficient mechanical activation of endothelial and vascular smooth muscle cells to maintain basal NO release and low intracellular Ca in the smooth muscle cells in large arteries. Both phenomena may play a vital role in maintaining the high compliance of large arteries.
大的弹性动脉缓冲源自左心室的压力波，并且比肌性动脉持续暴露于更高幅度的周期性拉伸（10%）（肌性动脉为2%）。然而，作为内皮细胞和平滑肌细胞功能的关键因素，周期性拉伸从未在小鼠主动脉段中进行过研究。为了研究周期性拉伸对小鼠主动脉段血管反应性的影响，我们使用啮齿动物振荡张力装置来研究动脉顺应性（ROTSAC）。将主动脉段在两个可变预负荷之间以6 - 600次/分钟的频率夹紧，从而模拟左心室收缩期的扩张和舒张期的回弹。选择对应于不同跨壁压力的预负荷，以对应低、正常或高幅度的周期性拉伸。在不同时间间隔，中断周期性拉伸，对主动脉段进行后负荷，并在不存在和存在300 μM L - NAME（内皮型一氧化氮合酶抑制剂）和/或35 μM地尔硫䓬（电压门控钙通道阻滞剂）的情况下，用2 μM去氧肾上腺素进行α - 肾上腺素能刺激来测量等长收缩。与低幅度（<10 mN）或低频（0.1 Hz）的静态或周期性拉伸相比，生理幅度（>10 mN）和频率（1 - 10 Hz）的周期性拉伸在安装后随时间能更好地保持基础一氧化氮释放。通过添加乙酰胆碱刺激一氧化氮释放来使去氧肾上腺素预收缩的段舒张不受周期性拉伸的影响。在不存在基础一氧化氮释放（即存在L - NAME）的情况下，与异常的周期性拉伸相比，生理性的周期性拉伸降低了基线张力，在无细胞外钙时减弱了去氧肾上腺素的相性收缩，并使较小的强直性收缩更多地从电压门控钙通道介导转变为非选择性阳离子通道介导。数据突出了充分机械激活内皮细胞和血管平滑肌细胞以维持大动脉中基础一氧化氮释放和平滑肌细胞中低细胞内钙的必要性。这两种现象可能在维持大动脉的高顺应性中起至关重要的作用。
