Department of Internal Medicine, Catholic University, Rome, Italy.
Department of Internal Medicine, Tor Vergata University, Rome, Italy.
Acta Physiol (Oxf). 2017 Jan;219(1):124-137. doi: 10.1111/apha.12630. Epub 2015 Dec 12.
Hyperpolarization causing smooth muscle relaxation contributes to the maintenance of vascular homeostasis, particularly in small-calibre arteries and arterioles. It may also become a compensatory vasodilator mechanism upregulated in states with impaired nitric oxide (NO) availability. Bioassay of vascular hyperpolarization in the human circulation has been hampered by the complexity of mechanisms involved and the limited availability of investigational tools. Firm evidence, however, supports the notion that hyperpolarization participates in the regulation of resting vasodilator tone and vascular reactivity in healthy subjects. In addition, an enhanced endothelium-derived hyperpolarization contributes to both resting and agonist-stimulated vasodilation in a variety of cardiovascular risk conditions and disease. Thus, hyperpolarization mediated by epoxyeicosatrienoic acids (EETs) and H O has been observed in coronary arterioles of patients with coronary artery disease. Similarly, ouabain-sensitive and EETs-mediated hyperpolarization has been observed to compensate for NO deficiency in patients with essential hypertension. Moreover, in non-hypertensive patients with multiple cardiovascular risk factors and in hypercholesterolaemia, K channel-mediated vasodilation appears to be activated. A novel paradigm establishes that perivascular adipose tissue (PVAT) is an additional regulator of vascular tone/function and endothelium is not the only agent in vascular hyperpolarization. Indeed, some PVAT-derived relaxing substances, such as adiponectin and angiotensin 1-7, may exert anticontractile and vasodilator actions by the opening of K channels in smooth muscle cells. Conversely, PVAT-derived factors impair coronary vasodilation via differential inhibition of some K channels. In view of adipose tissue abnormalities occurring in human obesity, changes in PVAT-dependent hyperpolarization may be relevant for vascular dysfunction also in this condition.
超极化引起平滑肌松弛有助于维持血管内环境稳定，尤其是在小动脉和小动脉中。在一氧化氮（NO）供应受损的情况下，它也可能成为一种代偿性血管舒张机制。由于涉及的机制复杂，以及研究工具的有限可用性，人类循环中超极化的生物测定一直受到阻碍。然而，有确凿证据支持这样一种观点，即超极化参与了健康受试者静息血管舒张张力和血管反应性的调节。此外，增强的内皮衍生超极化有助于各种心血管风险条件和疾病中的静息和激动剂刺激血管舒张。因此，在患有冠状动脉疾病的患者的冠状动脉小动脉中观察到由环氧二十碳三烯酸（EETs）和 H O 介导的超极化。同样，在患有原发性高血压的患者中观察到对钠泵敏感和 EETs 介导的超极化以补偿 NO 缺乏。此外，在患有多种心血管危险因素和高胆固醇血症的非高血压患者中，似乎激活了 K 通道介导的血管舒张。一个新的范例确立了血管周围脂肪组织（PVAT）是血管张力/功能的另一个调节剂，内皮并不是血管超极化的唯一调节剂。事实上，一些源自 PVAT 的舒张物质，如脂联素和血管紧张素 1-7，可能通过平滑肌细胞中 K 通道的开放发挥抗收缩和血管舒张作用。相反，源自 PVAT 的因子通过差异抑制某些 K 通道来损害冠状动脉舒张。鉴于人类肥胖中发生的脂肪组织异常，PVAT 依赖性超极化的变化在这种情况下也可能与血管功能障碍有关。
