Granado Miriam, Rubio Carmen, Amor Sara, Monge Luis, Fernández Nuria, Carreño-Tarragona Gonzalo, Carrascosa José M, García-Villalón Ángel Luis
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, 28029 Madrid, Spain; CIBER Fisiopatología de Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
Centro de Biología Molecular Severo Ochoa, UAM-CSIC, Facultad de Ciencias, Universidad Autónoma, 28049 Madrid, Spain.
Exp Gerontol. 2014 Dec;60:183-9. doi: 10.1016/j.exger.2014.10.018. Epub 2014 Nov 1.
Aging is associated with alterations in the cardiovascular system such as increased vasoconstriction and decreased vasodilatation. Some of these changes are partially reversed by caloric restriction. Endothelin-1 is a potent vasoconstrictor which levels increased with age. The aim of this study is to analyze the role of endothelin-1 in the cardiac and coronary changes induced by age and whether these changes may be attenuated by a three-month caloric restriction.
Hearts from young (3 months old), aged (24 months old) and aged rats after 3 months of caloric restriction were perfused according to the Langendorff technique. Coronary vasoconstriction to endothelin-1 was reduced in old rats, and endothelin-1 increased myocardial contractility (dP/dt) and heart rate in old but not in young rats. These changes observed in old rats were partly reversed by caloric restriction. Also, in the myocardial tissue of old rats the gene expression of endothelin-1, inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-a) was increased, and the gene expression of endothelin ETB receptors and endothelial nitric oxide syntase (eNOS) was reduced, compared with young rats. Aging induced changes in the expression of ETB receptors and eNOS were reversed by caloric restriction.
These results suggest that aging produces alterations in myocardial and coronary responses to endothelin-1, that may be related to changes in expression of nitric oxide synthases and/or endothelin receptor subtypes, with some of these changes being prevented by caloric restriction.
衰老与心血管系统的改变相关，如血管收缩增强和血管舒张减弱。热量限制可部分逆转其中一些变化。内皮素 -1 是一种强效血管收缩剂，其水平随年龄增长而升高。本研究的目的是分析内皮素 -1 在衰老诱导的心脏和冠状动脉变化中的作用，以及这些变化是否可通过三个月的热量限制得到缓解。
根据 Langendorff 技术对年轻（3 个月大）、老年（24 个月大）以及热量限制 3 个月后的老年大鼠的心脏进行灌注。老年大鼠对内皮素 -1 的冠状动脉收缩反应减弱，内皮素 -1 可增加老年大鼠的心肌收缩力（dP/dt）和心率，而对年轻大鼠无此作用。热量限制可部分逆转老年大鼠中观察到的这些变化。此外，与年轻大鼠相比，老年大鼠心肌组织中内皮素 -1、诱导型一氧化氮合酶（iNOS）和肿瘤坏死因子α（TNF -a）的基因表达增加，内皮素 ETB 受体和内皮型一氧化氮合酶（eNOS）的基因表达减少。热量限制可逆转衰老诱导的 ETB 受体和 eNOS 表达变化。
这些结果表明，衰老会导致心肌和冠状动脉对内皮素 -1 的反应发生改变，这可能与一氧化氮合酶和/或内皮素受体亚型的表达变化有关，其中一些变化可通过热量限制来预防。
