Mose Frank H, Larsen Thomas, Jensen Janni M, Hansen Annebirthe B, Bech Jesper N, Pedersen Erling B
University Clinic in Nephrology and Hypertension, Department of Medical Research and University of Aarhus.
Scand J Clin Lab Invest. 2014 Jan;74(1):8-19. doi: 10.3109/00365513.2013.855942. Epub 2013 Nov 21.
Statins have beneficial effects on cardiovascular morbidity and mortality independently of reduction of plasma cholesterol.
In patients with type 2 diabetes and nephropathy, chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-NMMA as an inhibitor of NO production. We performed a randomized, placebo-controlled, crossover study, using atorvastatin/placebo treatment for five days with a standardized diet and fluid intake. We measured brachial BP (bBP), central BP (cBP), GFR, urinary output (OU), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary excretion of albumin (UAER and UACR), AQP2 (u-AQP2) and ENaC (u-ENaCγ) and plasma concentrations of vasoactive hormones: renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide.
During atorvastatin and placebo treatment, L-NMMA infusion, changed the effect variables significantly, but to the same extent, i.e. an increase in bBP and cBP, and a decrease in GFR, OU, CH2O, FENa, u-AQP2 and u-ENaCγ. In addition, renin and angiotensin II was reduced, aldosterone increased, and vasopressin, endothelin-1 and brain natriuretic hormone unchanged.
During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, atorvastatin did not change nitric oxide availability in type 2 diabetics with nephropathy.
他汀类药物对心血管疾病的发病率和死亡率具有有益作用，且独立于血浆胆固醇降低之外。
在患有2型糖尿病和肾病（慢性肾脏病II - III期）的患者中，我们使用L - NMMA作为一氧化氮生成抑制剂，检验阿托伐他汀可增加全身和肾脏一氧化氮（NO）可用性的假设。我们进行了一项随机、安慰剂对照、交叉研究，采用阿托伐他汀/安慰剂治疗5天，并控制标准化饮食和液体摄入量。我们测量了肱动脉血压（bBP）、中心血压（cBP）、肾小球滤过率（GFR）、尿量（OU）、自由水清除率（CH2O）、钠分数排泄率（FENa）、尿白蛋白排泄量（UAER和UACR）、水通道蛋白2（u - AQP2）和上皮钠通道（u - ENaCγ），以及血管活性激素的血浆浓度：肾素、血管紧张素II、醛固酮、精氨酸加压素、内皮素 - 1和脑钠肽。
在阿托伐他汀和安慰剂治疗期间，输注L - NMMA显著改变了效应变量，但程度相同，即bBP和cBP升高，GFR、OU、CH2O、FENa、u - AQP2和u - ENaCγ降低。此外，肾素和血管紧张素II降低，醛固酮升高，而加压素、内皮素 - 1和脑钠激素不变。
在阿托伐他汀和安慰剂治疗期间，一氧化氮合成的抑制在肱动脉和中心血压、GFR、肾小管功能和血管活性激素方面引起相同的反应。因此，阿托伐他汀并未改变患有肾病的2型糖尿病患者的一氧化氮可用性。
