Tsuchida H, Imai G, Shima Y, Satoh T, Owada S
Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki, Japan.
Hypertens Res. 2001 Mar;24(2):127-35. doi: 10.1291/hypres.24.127.
Obesity-related non-insulin dependent diabetes mellitus (NIDDM) is frequently accompanied by hypertension. The present study was designed to clarify this mechanism. We first determined the blood pressure in male Wistar fatty rats (WFR), one of the NIDDM model rats, and in Wistar lean rats (WLR) as the control, with a normal (0.7% NaCl) or high (7% NaCl) salt diet. We observed no difference in systolic and mean blood pressures between WFR and WLR. WFR, however, became extremely hypertensive as a result of ingesting the high salt diet. We next investigated the mechanism for sodium sensitivity in WFR. Although the urinary excretion of dopamine (DA), a potent natriuretic factor, which reflects the ability for renal DA production, was preserved in WFR, the sodium balance with the high salt diet was positive. Moreover, Na-K-ATPase activity in isolated proximal convoluted tubules (PCT) from WFR with a normal salt diet was significantly (p<0.05) higher than that from WLR. A high salt load produced a significant (p<0.05) decrease in Na-K-ATPase activity in WLR but not in WFR. Similarly, Na-K-ATPase activity in WLR with a normal salt diet was significantly (p<0.05) inhibited by DA (10(-5) M), but this was not true in WFR. Furthermore, urinary excretion of norepinephrine in WFR with a high salt diet was the highest among all the groups. These results indicate that WFR tend to develop salt-sensitive hypertension that could be caused by the excessive sodium retention occurring as the results of a defective dopaminergic system in the kidney that fails to inhibit Na-K-ATPase activity. Augmentation of the renal sympathetic nervous system may play some role in this setting.
肥胖相关的非胰岛素依赖型糖尿病（NIDDM）常伴有高血压。本研究旨在阐明其机制。我们首先测定了雄性Wistar肥胖大鼠（WFR）（NIDDM模型大鼠之一）和作为对照的Wistar瘦大鼠（WLR）在正常（0.7%氯化钠）或高盐（7%氯化钠）饮食条件下的血压。我们观察到WFR和WLR之间的收缩压和平均血压没有差异。然而，WFR因摄入高盐饮食而血压极度升高。接下来，我们研究了WFR中钠敏感性的机制。尽管反映肾脏多巴胺（DA）生成能力的强效利钠因子多巴胺的尿排泄在WFR中得以保留，但高盐饮食时的钠平衡为正值。此外，正常盐饮食的WFR分离的近端小管（PCT）中的钠钾ATP酶活性显著（p<0.05）高于WLR。高盐负荷使WLR中的钠钾ATP酶活性显著（p<0.05）降低，但WFR中未出现这种情况。同样，正常盐饮食的WLR中的钠钾ATP酶活性被DA（10⁻⁵ M）显著（p<0.05）抑制，但WFR中并非如此。此外，高盐饮食的WFR中去甲肾上腺素的尿排泄在所有组中最高。这些结果表明，WFR倾向于发生盐敏感性高血压，这可能是由于肾脏中多巴胺能系统缺陷导致钠潴留过多，无法抑制钠钾ATP酶活性所致。肾交感神经系统的增强可能在这种情况下起一定作用。
