Canessa M, Falkner B, Hulman S
Endocrine-Hypertension Division, Brigham and Women's Hospital, Boston, MA 02115.
Hypertension. 1993 Aug;22(2):204-13. doi: 10.1161/01.hyp.22.2.204.
To define the potential pathogenic role of hyperinsulinemia as a mediator of alterations in sodium transport, we have examined red blood cell Na(+)-H+ and Na(+)-Li+ exchanges in a young adult black population characterized for blood pressure and insulin-mediated glucose disposal. Normotensive and mildly hypertensive blacks (blood pressure, 120 +/- 2/76 +/- 2 and 139 +/- 3/94 +/- 2 mm Hg, respectively) with a mean age of 26.1 years were studied for insulin sensitivity with the euglycemic hyperinsulinemic clamp (molar index of insulin sensitivity, M/I = moles glucose metabolized/insulin in milliliters of plasma). Na(+)-H+ exchange (U = mmol/L cell.h) was measured before and after the insulin clamp as a function of cell pH to determine the maximum transport rate. In the normotensive subjects, 18 were insulin sensitive (M/I = 9.37 +/- 0.6 x 10(4)) and 4 were insulin resistant (M/I = 3.64 +/- 0.6 x 10(4)). In the hypertensive subjects, 4 were insulin sensitive (M/I = 9.15 +/- 1.1 x 10(4)) and 16 were insulin resistant (M/I = 3.02 +/- 0.3 x 10(4)). The maximum rate of Na(+)-H+ exchange was significantly higher in all hypertensive vs normotensive individuals (35 +/- 3 vs 23 +/- 3 U, P < .005). Na(+)-H+ exchange activity was higher in insulin-resistant vs insulin-sensitive hypertensive subjects (40 +/- 3 vs 20 +/- 2 U, P < .001) but not in insulin-resistant normotensive subjects. Na(+)-Li+ exchange was not different in hypertensive and normotensive individuals but was higher in all insulin-resistant compared with all insulin-sensitive subjects (0.26 +/- 0.03 vs 0.16 +/- 0.02 U, P < .01). Na(+)-Li+ exchange also was higher in insulin-resistant vs insulin-sensitive normotensive subjects (0.35 +/- 0.03 vs 0.15 +/- 0.02 U, P < .001) and in insulin-resistant hypertensive subjects vs insulin-sensitive normotensive subjects (0.24 +/- 0.03 vs 0.15 +/- 0.02 U, P < .001). A stepwise multiple regression analysis for all variables revealed that with Na(+)-H+ exchange as a dependent variable the main determinant was blood pressure, which in turn had insulin sensitivity as the main determinant. In conclusion, these results indicate that in hypertensive blacks, insulin-resistant glucose disposal is strongly associated with elevated red blood cell Na(+)-H+ exchange activity. Thus, despite impaired insulin-mediated glucose disposal, cellular Na+ gain via enhanced activity of Na(+)-H+ exchange is not blunted in hypertensive blacks.
为了确定高胰岛素血症作为钠转运改变介质的潜在致病作用，我们在一个以血压和胰岛素介导的葡萄糖处置为特征的年轻成年黑人人群中，研究了红细胞的Na(+)-H+和Na(+)-Li+交换。对平均年龄为26.1岁的血压正常和轻度高血压黑人（血压分别为120±2/76±2和139±3/94±2 mmHg），采用正常血糖高胰岛素钳夹技术研究胰岛素敏感性（胰岛素敏感性摩尔指数，M/I = 代谢的葡萄糖摩尔数/血浆毫升中的胰岛素）。在胰岛素钳夹前后，根据细胞pH值测量Na(+)-H+交换（U = mmol/L细胞·小时），以确定最大转运速率。在血压正常的受试者中，18人胰岛素敏感（M/I = 9.37±0.6×10(4)），4人胰岛素抵抗（M/I = 3.64±0.6×10(4)）。在高血压受试者中，4人胰岛素敏感（M/I = 9.15±1.1×10(4)），16人胰岛素抵抗（M/I = 3.02±0.3×10(4)）。所有高血压个体的Na(+)-H+交换最大速率显著高于血压正常个体（35±3 vs 23±3 U，P <.005）。胰岛素抵抗的高血压受试者的Na(+)-H+交换活性高于胰岛素敏感的高血压受试者（40±3 vs 20±2 U，P <.001），但胰岛素抵抗的血压正常受试者中并非如此。高血压和血压正常个体的Na(+)-Li+交换无差异，但所有胰岛素抵抗受试者的Na(+)-Li+交换高于所有胰岛素敏感受试者（0.26±0.03 vs 0.16±0.02 U，P <.01）。胰岛素抵抗的血压正常受试者与胰岛素敏感的血压正常受试者相比，Na(+)-Li+交换也更高（0.35±0.03 vs 0.15±0.02 U，P <.001），胰岛素抵抗的高血压受试者与胰岛素敏感的血压正常受试者相比也是如此（0.24±0.03 vs 0.15±0.02 U，P <.001）。对所有变量进行逐步多元回归分析显示，以Na(+)-H+交换为因变量时，主要决定因素是血压，而血压又以胰岛素敏感性为主要决定因素。总之，这些结果表明，在高血压黑人中，胰岛素抵抗的葡萄糖处置与红细胞Na(+)-H+交换活性升高密切相关。因此，尽管胰岛素介导的葡萄糖处置受损，但高血压黑人中通过增强Na(+)-H+交换活性导致的细胞内Na+增加并未减弱。
