Dengel D R, Goldberg A P, Mayuga R S, Kairis G M, Weir M R
Department of Medicine, University of Maryland School of Medicine, USA.
Hypertension. 1996 Jul;28(1):127-32. doi: 10.1161/01.hyp.28.1.127.
The development of insulin resistance may be an early step in the development of hypertension; however, the mechanism for this process is not known. The worsening of insulin resistance and hypertension could increase both systemic and glomerular capillary pressures and predispose an individual to renal injury. The purpose of this study was to examine the relationship of insulin resistance to glomerular hemodynamics and dietary salt intake in 10 older (68 +/- 6 years), obese (body mass index, 31 +/- 4 kg/m2), mildly hypertensive (151 +/- 8/82 +/- 2 mm Hg), sedentary subjects without clinical evidence of diabetes or renal disease. They were studied on separate days with radioisotopic renal clearances (glomerular filtration rate by 99mTc-diethylenetriaminepentaacetic acid urinary clearance; renal plasma flow by 131I-hippuran serum disappearance) and a two-dose (40 and 100 mU/m2 per minute) hyperinsulinemic euglycemic clamp for measurement of glucose disposal after 2 weeks of a 3-g and 2 weeks of a 10-g sodium diet. Glomerular filtration rate (68.1 +/- 7.7 to 78.0 +/- 6.6 mL/min per 1.73 m2, P = .08) and glomerular filtration fraction (0.21 +/- 0.02 to 0.22 +/- 0.02, P = .5) did not change significantly after dietary salt was increased. During low dietary salt intake, there was an inverse relationship between glomerular filtration fraction and glucose disposal rate (milligrams per kilogram fat-free mass per minute) at both low (r = -.70, P = .04) and high (r = -.83, P = .006) insulin levels. However, these relationships were attenuated during salt loading. This suggests that a greater degree of insulin resistance, not increased dietary salt, may predispose older mildly hypertensive subjects to renal injury by worsening renal hemodynamics through the elevation of glomerular filtration fraction and resultant glomerular hyperfiltration.
胰岛素抵抗的发展可能是高血压发生的早期步骤；然而，这一过程的机制尚不清楚。胰岛素抵抗和高血压的恶化会增加全身和肾小球毛细血管压力，并使个体易患肾损伤。本研究的目的是在10名年龄较大（68±6岁）、肥胖（体重指数，31±4kg/m²）、轻度高血压（151±8/82±2mmHg）、久坐不动且无糖尿病或肾脏疾病临床证据的受试者中，研究胰岛素抵抗与肾小球血流动力学及饮食盐摄入量之间的关系。在分别的日子里，对他们进行放射性核素肾清除率测定（用99mTc-二乙三胺五乙酸尿清除率测定肾小球滤过率；用131I-马尿酸血清消失率测定肾血浆流量），并在3g钠饮食2周和10g钠饮食2周后，采用双剂量（每分钟40和100mU/m²）高胰岛素正常血糖钳夹技术测量葡萄糖处置情况。饮食盐增加后，肾小球滤过率（每1.73m²从68.1±7.7降至78.0±6.6mL/min，P=0.08）和滤过分数（从0.21±0.02降至0.22±0.02，P=0.5）无显著变化。在低饮食盐摄入期间，无论低（r=-0.70，P=0.04）胰岛素水平还是高（r=-0.83，P=0.006）胰岛素水平，肾小球滤过分数与葡萄糖处置率（每千克去脂体重每分钟毫克数）之间均呈负相关。然而，在盐负荷期间这些关系减弱。这表明，更大程度的胰岛素抵抗而非增加的饮食盐，可能通过提高肾小球滤过分数和导致肾小球高滤过来恶化肾脏血流动力学，从而使老年轻度高血压受试者易患肾损伤。
