Bro Susanne, Bollano Entela, Brüel Annemarie, Olgaard Klaus, Nielsen Lars B
Department of Nephrology, Rigshospitalet, Copenhagen, Denmark.
Scand J Clin Lab Invest. 2008;68(7):660-6. doi: 10.1080/00365510802037272.
Kidney dysfunction is often associated with cardiac left ventricular hypertrophy and increased cardiovascular mortality.
The aim of this study was to find out whether this reflects direct effects of uraemia on the heart or is dependent on accompanying hypertension.
Apolipoprotein-E (apoE)-deficient C57BL/6 mice are resistant to development of hypertension after renal mass reduction. To evaluate the impact of uraemia without hypertension on the heart, apoE-deficient mice underwent 5/6 nephrectomy (NX) or sham operation (Sh) and were randomized to treatment with the angiotensin converting enzyme inhibitor enalapril (12 mg kg(-1) d(-1)) or no medication.
NX did not affect systolic blood pressure (BP), but reduced mean creatinine clearance, body weight and blood haemoglobin to 27% (p < 0.01), 82% (p < 0.0001) and 73% (p < 0.0001), respectively, of the values in Sh mice. Thirty-six weeks after NX, heart wet weight, echocardiographic estimates of left ventricular mass and left ventricular diastolic and systolic functions were similar in NX and Sh mice. NX did not increase cardiac fibrosis or cardiac mRNA expression of biglycan, whereas it decreased the mRNA expression of procollagen (p < 0.01). Enalapril reduced BP (p < 0.001), heart wet weight and estimated left ventricular mass in both NX (p < 0.01) and Sh mice (p < 0.05), but did not affect cardiac diastolic or systolic function. Conclusions. The results suggest that uraemia does not impair cardiac structure or function in apoE-deficient mice. Since NX has no effect on BP in apoE-deficient mice, the results may indicate that hypertension is important for development of left ventricular disease in uraemia.
肾功能不全常与心脏左心室肥厚及心血管死亡率增加相关。
本研究旨在查明这是否反映了尿毒症对心脏的直接作用，还是依赖于伴随的高血压。
载脂蛋白E（apoE）缺陷的C57BL/6小鼠在肾质量减少后对高血压的发展具有抗性。为评估无高血压的尿毒症对心脏的影响，对apoE缺陷小鼠进行5/6肾切除术（NX）或假手术（Sh），并随机分为接受血管紧张素转换酶抑制剂依那普利（12 mg kg⁻¹ d⁻¹）治疗或不接受药物治疗。
NX不影响收缩压（BP），但将平均肌酐清除率、体重和血红蛋白分别降至Sh小鼠相应值的27%（p < 0.01）、82%（p < 0.0001）和73%（p < 0.0001）。NX后36周，NX小鼠和Sh小鼠的心脏湿重、左心室质量的超声心动图估计值以及左心室舒张和收缩功能相似。NX未增加双糖链蛋白聚糖的心脏纤维化或心脏mRNA表达，而降低了前胶原的mRNA表达（p < 0.01）。依那普利降低了NX小鼠（p < 0.01）和Sh小鼠（p < 0.05）的BP、心脏湿重和估计的左心室质量，但不影响心脏舒张或收缩功能。结论。结果表明，尿毒症不会损害apoE缺陷小鼠的心脏结构或功能。由于NX对apoE缺陷小鼠的BP无影响，结果可能表明高血压对尿毒症中左心室疾病的发展很重要。
