RED-BLOOD-CELL SODIUM-PROTON EXCHANGE IN HYPERTENSIVE BLACKS WITH INSULIN-RESISTANT GLUCOSE DISPOSAL

To define the potential pathogenic role of hyperinsulinemia as a media tor of alterations in sodium transport, we have examined red blood cel l Na+-H+ and Na+-Li+ exchanges in a young adult black population chara cterized for blood pressure and insulin-mediated glucose disposal. Nor motensive 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 hy perinsulinemic clamp (molar index of insulin sensitivity, M/I=moles gl ucose 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 no rmotensive subjects, 18 were insulin sensitive (M/I = 9.37 +/- 0.6 x 1 0(4)) and 4 were insulin resistant (M/1=3.64 +/- 0.6 x 10(4)). In the hypertensive subjects, 4 were insulin sensitive (M/1=9.15 +/- 1.1 x 10 (4)) and 16 were insulin resistant (M/1=3.02 +/- 0.3 x 10(4)). The max imum rate of Na+-H+ exchange was significantly higher in all hypertens ive vs normotensive individuals (35 +/- 3 vs 23 +/- 3 U, P<.005). Na+- H+ exchange activity was higher in insulin-resistant vs insulin-sensit ive hypertensive subjects (40 +/- 3 vs 20 +/- 2 U, P<.001) but not in insulin-resistant normotensive subjects. Na+-Li+ exchange was not diff erent in hypertensive and normotensive individuals but was higher in a ll insulin-resistant compared with all insulin-sensitive subjects (0.2 6 +/- 0.03 vs 0.16 +/- 0.02 U, P<.01). Na+-Li+ exchange also was highe r in insulin-resistant vs insulin-sensitive normotensive subjects (0.3 5 +/- 0.03 vs 0.15 +/- 0.02 U, P<.001) and in insulin-resistant hypert ensive subjects vs insulin-sensitive normotensive subjects (0.24 +/- 0 .03 vs 0.15 +/- 0.02 U, P<.001). A stepwise multiple regression analys is for all variables revealed that with Na+-H+ exchange as a dependent variable the main determinant was blood pressure, which in turn had i nsulin sensitivity as the main determinant. In conclusion, these resul ts indicate that in hypertensive blacks, insulin-resistant glucose dis posal is strongly associated with elevated red blood cell Na+-H+ excha nge activity. Thus, despite impaired insulin-mediated glucose disposal , cellular Na+ gain via enhanced activity of Na+-H+ exchange is not bl unted in hypertensive blacks.