Mourmoura Evangelia, Couturier Karine, Hininger-Favier Isabelle, Malpuech-Brugère Corinne, Azarnoush Kasra, Richardson Melanie, Demaison Luc
Laboratoire de Bioénergétique Fondamentale et Appliquée, INSERM U1055, Université Joseph Fourier, BP 53, 38041, Grenoble cedex 09, France.
Age (Dordr). 2014;36(4):9670. doi: 10.1007/s11357-014-9670-z. Epub 2014 Jul 4.
This study was aimed at characterizing the functional progression of the endothelial (ECs) and smooth muscle cells (SMCs) of the coronary microvasculature between youth and old age, as well as at determining the mechanisms of the observed changes on the basis of the glucose tolerance, mitochondrial energy metabolism, and oxidative stress. Male rats were divided into four age groups (3, 6, 11, and 17 months for the young (Y), young adult (YA), middle-aged (MA), and old (O) animals). The cardiac mechanical function, endothelial-dependent dilatation (EDD) and endothelial-independent dilatation (EID) of the coronary microvasculature were determined in a Langendorff preparation. The mitochondrial respiration and H2O2 production were evaluated and completed by ex vivo measurements of oxidative stress. EDD progressively decreased from youth to old age. The relaxation properties of the SMCs, although high in the Y rats, decreased drastically between youth and young adulthood and stabilized thereafter, paralleling the reduction of mitochondrial oxidative phosphorylation. The ECs dilatation activity, low at youth, was stimulated in YA animals and returned to their initial level at middle age. That parameter followed faithfully the progression of the amount of active cardiac endothelial nitric oxide synthase and whole body glucose intolerance. In conclusion, the progressive decrease in EDD occurring with aging is due to different functional behaviors of the ECs and SMCs, which appear to be associated with the systemic glucose intolerance and cardiac energy metabolism.
本研究旨在描述青年和老年之间冠状动脉微血管内皮细胞（ECs）和平滑肌细胞（SMCs）的功能进展情况，并基于葡萄糖耐量、线粒体能量代谢和氧化应激来确定所观察到变化的机制。雄性大鼠被分为四个年龄组（3个月、6个月、11个月和17个月，分别对应青年（Y）、青年成年（YA）、中年（MA）和老年（O）动物）。在Langendorff离体心脏灌流装置中测定心脏机械功能、冠状动脉微血管的内皮依赖性舒张（EDD）和非内皮依赖性舒张（EID）。通过体外氧化应激测量来评估和完成线粒体呼吸及过氧化氢生成情况。EDD从青年到老年逐渐降低。SMCs的舒张特性在Y组大鼠中虽较高，但在青年和青年成年之间急剧下降，此后趋于稳定，这与线粒体氧化磷酸化的降低情况平行。ECs的舒张活性在青年时较低，在YA组动物中受到刺激，并在中年时恢复到初始水平。该参数忠实地跟随活性心脏内皮型一氧化氮合酶量的变化以及全身葡萄糖不耐受情况。总之，随着年龄增长EDD的逐渐降低是由于ECs和SMCs的不同功能行为所致，这些行为似乎与全身葡萄糖不耐受和心脏能量代谢有关。
