Tofovic S P, Jackson E K
Center for Clinical Pharmacology, Department of Medicine, University of Pittsburgh Medical Center, Pennsylvania 15213-2582, USA.
J Cardiovasc Pharmacol. 1999 Mar;33(3):360-6. doi: 10.1097/00005344-199903000-00003.
Our previous studies supported the hypothesis that prolonged administration of caffeine to animals with high-renin hypertension causes progressive deterioration of renal function. However, thus far this hypothesis has been tested with only a few animal models of hypertension. The aim of this study was to test this hypothesis further by investigating the effects of long-term caffeine consumption on renal function in adult spontaneously hypertensive heart failure (SHHF/Mcc-fa(cp)) rats, another model of high-renin hypertension. Lean, male, 9-month-old SHHF/Mcc-fa(cp) rats were randomized to receive either normal drinking water (control group) or drinking water containing 0.1% caffeine (caffeine group) for 20 weeks. No changes in body weight, food and fluid intake, urine volume, and sodium and potassium excretion were found in conscious SHHF/Mcc-fa(cp) rats after 10 or 20 weeks of caffeine treatment. However, caffeine treatment accelerated the time-related decline in renal function and augmented urinary protein excretion. Ten weeks into the protocol, creatinine clearance was 3.6+/-0.4 and 5.7+/-0.9 L/kg/day in the caffeine group and control group, respectively (p<0.02), whereas 20 weeks into the study, creatinine clearance was similarly diminished in both groups. Proteinuria was greater in the caffeine group compared with the control group at both 10 (928+/-131 vs. 439+/-21 mg/kg/day, respectively; p<0.02) and 20 weeks (1,202+/-196 vs. 603+/-30 mg/kg/day, respectively; p<0.01) into the protocol. After 20 weeks, all animals were anesthetized and instrumented. Caffeine treatment for 20 weeks had no effects on blood pressure, heart rate, or vascular resistance in four examined vascular beds (abdominal aorta and renal, carotid, and mesenteric arteries). No changes in renal hemodynamics and electrolyte excretion were found, whereas significantly lower glomerular filtration rate (GFR; inulin clearance) and creatinine clearance (p<0.05) were observed in caffeine-treated animals. These data support our hypothesis that prolonged consumption of caffeine has adverse effects on renal function, in high-renin hypertension.
我们之前的研究支持这样一种假说，即对高肾素性高血压动物长期给予咖啡因会导致肾功能进行性恶化。然而，迄今为止，这一假说仅在少数高血压动物模型中得到验证。本研究的目的是通过研究长期摄入咖啡因对成年自发性高血压心力衰竭（SHHF/Mcc-fa(cp)）大鼠（另一种高肾素性高血压模型）肾功能的影响，进一步验证这一假说。将瘦的、雄性、9月龄的SHHF/Mcc-fa(cp)大鼠随机分为两组，一组给予正常饮用水（对照组），另一组给予含0.1%咖啡因的饮用水（咖啡因组），持续20周。在咖啡因处理10周或20周后，清醒的SHHF/Mcc-fa(cp)大鼠的体重、食物和液体摄入量、尿量以及钠和钾排泄均未发现变化。然而，咖啡因处理加速了肾功能随时间的下降，并增加了尿蛋白排泄。在实验方案进行到10周时，咖啡因组和对照组的肌酐清除率分别为3.6±0.4和5.7±0.9 L/kg/天（p<0.02），而在研究进行到20周时，两组的肌酐清除率均同样降低。在实验方案进行到10周（分别为928±131和439±21 mg/kg/天；p<0.02）和20周（分别为1202±196和603±30 mg/kg/天；p<0.01）时，咖啡因组的蛋白尿均高于对照组。20周后，所有动物均被麻醉并进行仪器监测。咖啡因处理20周对所检测的四个血管床（腹主动脉、肾动脉、颈动脉和肠系膜动脉）的血压、心率或血管阻力均无影响。未发现肾血流动力学和电解质排泄有变化，而在咖啡因处理的动物中观察到肾小球滤过率（GFR；菊粉清除率）和肌酐清除率显著降低（p<0.05）。这些数据支持了我们的假说，即在高肾素性高血压中，长期摄入咖啡因对肾功能有不良影响。
