Bruno Rosa Maria, Duranti Emiliano, Ippolito Chiara, Segnani Cristina, Bernardini Nunzia, Di Candio Giulio, Chiarugi Massimo, Taddei Stefano, Virdis Agostino
From the Histology Unit (C.I., C.S., N.B.), Internal Medicine Unit (R.M.B., E.D., S.T., A.V.) of Department of Clinical and Experimental Medicine, Emergency Surgery Unit (M.C.) of Department of Surgery, Medical, Molecular, and Critical Area Pathology, and General Surgery Unit (G.D.C.) of Department of Oncology Transplantation and New Technologies, University of Pisa, Italy.
Hypertension. 2017 Jan;69(1):71-78. doi: 10.1161/HYPERTENSIONAHA.116.08041. Epub 2016 Oct 31.
We evaluated whether vascular remodeling is present in physiological aging and whether hypertension accelerates the aging process for vascular function and structure. Small arteries from 42 essential hypertensive patients (HT) and 41 normotensive individuals (NT) were dissected after subcutaneous biopsy. Endothelium-dependent vasodilation (pressurized myograph) was assessed by acetylcholine, repeated under the nitric oxide synthase inhibitor N-nitro-l-arginine methylester or the antioxidant tempol. Structure was evaluated by media-lumen ratio (M/L). Intravascular oxidative generation and collagen deposition were assessed. Inhibition by N-nitro-l-arginine methylester on ACh was inversely related to age in both groups (P<0.0001) and blunted in HT versus NT for each age range. In NT, tempol enhanced endothelial function in the oldest subgroup; in HT, the potentiating effect started earlier. HT showed an increased M/L (P<0.001) versus control. In both groups, M/L was directly related to age (P<0.0001). M/L was greater in HT, starting from 31 to 45 years range. A significant age-hypertension interaction occurred (P=0.0009). In NT, intravascular superoxide emerged in the oldest subgroup, whereas it appeared earlier among HT. Among NT, aged group displayed an increment of collagen fibers versus young group. In HT, collagen deposition was already evident in youngest, with a further enhancement in the aged group. In small arteries, ageing shows a eutrophic vascular remodeling and a reduced nitric oxide availability. Oxidative stress and fibrosis emerge in advanced age. In HT, nitric oxide availability is early reduced, but the progression rate with age is similar. Structural alterations include wide collagen deposition and intravascular reactive oxygen species, and the progression rate with age is steeper.
我们评估了生理性衰老过程中是否存在血管重塑,以及高血压是否会加速血管功能和结构的衰老进程。对42例原发性高血压患者(HT)和41例血压正常个体(NT)进行皮下活检后,解剖其小动脉。通过乙酰胆碱评估内皮依赖性血管舒张功能(压力肌动描记法),并在一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯或抗氧化剂tempol作用下重复进行评估。通过中膜-管腔比(M/L)评估血管结构。评估血管内氧化产物生成和胶原沉积情况。N-硝基-L-精氨酸甲酯对乙酰胆碱的抑制作用在两组中均与年龄呈负相关(P<0.0001),且在每个年龄范围内,HT组相对于NT组的抑制作用减弱。在NT组中,tempol在年龄最大的亚组中增强了内皮功能;在HT组中,增强作用开始得更早。与对照组相比,HT组的M/L增加(P<0.001)。在两组中,M/L均与年龄呈正相关(P<0.0001)。HT组的M/L从31至45岁年龄段开始就高于NT组。存在显著的年龄-高血压交互作用(P=0.0009)。在NT组中,血管内超氧化物在年龄最大的亚组中出现,而在HT组中出现得更早。在NT组中,老年组相对于年轻组胶原纤维增加。在HT组中,最年轻组就已出现明显的胶原沉积,老年组进一步增加。在小动脉中,衰老表现为营养性血管重塑和一氧化氮可用性降低。氧化应激和纤维化在老年期出现。在HT组中,一氧化氮可用性早期降低,但随年龄的进展速率相似。结构改变包括广泛的胶原沉积和血管内活性氧,且随年龄的进展速率更陡峭。