Masuo Kazuko, Katsuya Tomohiro, Sugimoto Ken, Kawaguchi Hideki, Rakugi Hiromi, Ogihara Toshio, Tuck Michael L
Human Neurotransmitter Laboratory, Baker Heart Research Institute, Melbourne, Australia.
Hypertens Res. 2007 Jun;30(6):503-11. doi: 10.1291/hypres.30.503.
Renal injury is common in obesity and hypertension. In the present study, we examined relationships between renal function alterations, plasma norepinephrine (NE), and beta2-adrenoceptor polymorphisms in a longitudinal design over 5 years. In 219 nonobese, normotensive men with entry-normal renal function, we measured serum blood urea nitrogen (BUN), creatinine, creatinine clearance, plasma NE, homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), total body fat mass, and blood pressure (BP) annually for 5 years. beta2 (Arg16Gly, Gln27Glu)-adrenoceptor polymorphisms were determined. The subjects were stable in body weight and BP (<10%) for 5 years. High plasma NE was defined as > or =mean+1 SD at entry. Thirty-seven subjects had entry-high plasma NE and 182 were entry-normal. Entry-high plasma NE subjects had significantly greater total body fat mass and plasma NE and significantly lower creatinine clearance at entry and throughout the study. Increases in BMI, fat mass, BP, plasma NE, BUN, and creatinine, as well as the reduction in creatinine clearance in the 5 years, were significantly greater in entry-high NE subjects. These subjects had significantly higher frequencies of the Gly16 allele of beta2-adrenoceptor polymorphisms. Throughout the study, subjects carrying the Gly16 allele had higher plasma NE, HOMA-IR, and fat mass, and significantly greater reductions in creatinine clearance. Plasma NE at entry was a determinant variable for changes in BUN, creatinine, and creatinine clearance over the 5-year period in multiple regression analysis. In conclusion, high plasma NE at entry, associated with the Gly16 allele of the beta2-adrenoceptor polymorphisms, predict renal function deterioration (seen in elevations of BUN and creatinine and reduction of creatinine clearance) over a 5-year period accompanying further heightened sympathetic nerve activity and deterioration of insulin resistance.
肾损伤在肥胖症和高血压患者中很常见。在本研究中，我们采用纵向设计，对5年期间肾功能改变、血浆去甲肾上腺素（NE）和β2 - 肾上腺素能受体多态性之间的关系进行了研究。在219名肾功能正常的非肥胖、血压正常男性中，我们每年测量血清尿素氮（BUN）、肌酐、肌酐清除率、血浆NE、胰岛素抵抗稳态模型评估（HOMA - IR）、体重指数（BMI）、全身脂肪量和血压（BP），为期5年。测定了β2（Arg16Gly，Gln27Glu）- 肾上腺素能受体多态性。这些受试者在5年内体重和血压保持稳定（变化<10%）。高血浆NE定义为入组时≥均值 + 1个标准差。37名受试者入组时血浆NE高，182名入组时正常。入组时血浆NE高的受试者全身脂肪量和血浆NE显著更高，入组时及整个研究期间肌酐清除率显著更低。在5年中，入组时血浆NE高的受试者BMI、脂肪量、BP、血浆NE、BUN和肌酐的增加以及肌酐清除率的降低显著更大。这些受试者β2 - 肾上腺素能受体多态性的Gly16等位基因频率显著更高。在整个研究过程中，携带Gly16等位基因的受试者血浆NE、HOMA - IR和脂肪量更高，肌酐清除率的降低也显著更大。在多元回归分析中，入组时的血浆NE是5年期间BUN、肌酐和肌酐清除率变化的决定变量。总之，入组时高血浆NE与β2 - 肾上腺素能受体多态性的Gly16等位基因相关，可预测在5年期间肾功能恶化（表现为BUN和肌酐升高以及肌酐清除率降低），同时伴有交感神经活动进一步增强和胰岛素抵抗恶化。
