β3-肾上腺素能受体对心血管系统一氧化氮的调节。
Beta 3-adrenoreceptor regulation of nitric oxide in the cardiovascular system.
机构信息
Johns Hopkins University School of Medicine, Division of Cardiology, Baltimore, MD 21205, USA.
出版信息
J Mol Cell Cardiol. 2010 Jun;48(6):1088-95. doi: 10.1016/j.yjmcc.2010.02.011. Epub 2010 Feb 23.
Abstract
The presence of a third beta-adrenergic receptor (beta 3-AR) in the cardiovascular system has challenged the classical paradigm of sympathetic regulation by beta1- and beta2-adrenergic receptors. While beta 3-AR's role in the cardiovascular system remains controversial, increasing evidence suggests that it serves as a "brake" in sympathetic overstimulation - it is activated at high catecholamine concentrations, producing a negative inotropic effect that antagonizes beta1- and beta2-AR activity. The anti-adrenergic effects induced by beta 3-AR were initially linked to nitric oxide (NO) release via endothelial NO synthase (eNOS), although more recently it has been shown under some conditions to increase NO production in the cardiovascular system via the other two NOS isoforms, namely inducible NOS (iNOS) and neuronal NOS (nNOS). We summarize recent findings regarding beta 3-AR effects on the cardiovascular system and explore its prospective as a therapeutic target, particularly focusing on its emerging role as an important mediator of NO signaling in the pathogenesis of cardiovascular disorders.
摘要
心血管系统中存在第三种β肾上腺素受体（β3-AR），这对经典的β1 和β2 肾上腺素受体介导的交感神经调节范式提出了挑战。虽然β3-AR 在心血管系统中的作用仍存在争议，但越来越多的证据表明，它作为一种“刹车”来对抗交感神经过度刺激——在高儿茶酚胺浓度下被激活，产生负性变力作用，拮抗β1 和β2-AR 活性。β3-AR 诱导的抗肾上腺素作用最初与内皮型一氧化氮合酶（eNOS）介导的一氧化氮（NO）释放有关，尽管最近的研究表明，在某些条件下，它可以通过另外两种NOS 同工酶，即诱导型 NOS（iNOS）和神经元型 NOS（nNOS），增加心血管系统中的 NO 产生。我们总结了最近关于β3-AR 对心血管系统影响的发现，并探讨了其作为治疗靶点的潜力，特别是特别关注它作为心血管疾病发病机制中重要的 NO 信号转导介质的新兴作用。
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