Shrikhande Gautam, Khaodhiar Lalita, Scali Salvatore, Lima Christina, Hubbard Matthew, Dudley Katherine, Ganda Om, Ferran Christiane, Veves Aristidis
Immunobiology Research Center and Division of Vascular Surgery, Harvard Medical School, Boston, Massachusetts.
J Vasc Surg. 2006 Apr;43(4):760-70; discussion 770-1. doi: 10.1016/j.jvs.2005.12.059.
To examine the effect of a 12-week daily treatment with 160 mg of valsartan, an angiotensin II receptor blocker, on the microcirculation and macrocirculation of type 2 diabetic patients (T2DM) and healthy subjects.
This was a prospective, randomized, double-blind, placebo-controlled crossover study. Thirteen T2DM with no severe complications and 13 healthy subjects completed the trial.
Treatment with valsartan in T2DM improved the resting forearm skin blood flow and increased the resting brachial artery diameter but had no effects on arterial blood pressure, large vessel vascular reactivity, or carotid intima-media thickness. Resting skin blood flow increased by 60% (2%-90%; median and 25th-75th percentiles) during valsartan treatment and by only 2% (-22% to 27%) during placebo treatment (P < .05). No changes were observed in the nondiabetic subjects. Immunostaining studies of forearm skin biopsy samples from T2DM and healthy subjects showed that valsartan reduced poly(adenosine diphosphate-ribose) polymerase (PARP) activity in 50% (6/12) of the subjects. PARP activity remained unchanged in placebo-treated subjects (P < .02). In addition, valsartan treatment increased CD31 staining in 33% (4/12) of the subjects, whereas no change was noted in sequential skin biopsy samples of placebo-treated subjects (P = .057). Valsartan had no effect on the biochemical markers of endothelial cell activation and other cytokines, including CAMs, interleukin 6, tumor necrosis factor alpha, C-reactive protein, adiponectin, and plasma activator inhibitor 1.
Valsartan increases the resting skin blood flow in T2DM, likely through reduction of PARP activity.
研究血管紧张素II受体阻滞剂缬沙坦每日160mg治疗12周对2型糖尿病患者（T2DM）和健康受试者微循环及大循环的影响。
这是一项前瞻性、随机、双盲、安慰剂对照的交叉研究。13例无严重并发症的T2DM患者和13例健康受试者完成了试验。
T2DM患者使用缬沙坦治疗可改善静息状态下前臂皮肤血流，增加静息状态下肱动脉直径，但对动脉血压、大血管血管反应性或颈动脉内膜中层厚度无影响。缬沙坦治疗期间静息皮肤血流增加60%（2%-90%；中位数和第25-75百分位数），而安慰剂治疗期间仅增加2%（-22%至27%）（P<.05）。非糖尿病受试者未观察到变化。对T2DM患者和健康受试者前臂皮肤活检样本的免疫染色研究表明，缬沙坦使50%（6/12）的受试者多聚（二磷酸腺苷-核糖）聚合酶（PARP）活性降低。安慰剂治疗的受试者PARP活性保持不变（P<.02）。此外，缬沙坦治疗使33%（4/12）的受试者CD31染色增加，而安慰剂治疗的受试者连续皮肤活检样本中未观察到变化（P=.057）。缬沙坦对内皮细胞活化的生化标志物和其他细胞因子，包括细胞黏附分子、白细胞介素6、肿瘤坏死因子α、C反应蛋白、脂联素和血浆纤溶酶原激活物抑制剂1无影响。
缬沙坦可能通过降低PARP活性增加T2DM患者的静息皮肤血流。
