EFFECTS OF AGING ON THE INSULIN ACTIONS FOR THE GLUCOSE-METABOLISM AND RENAL-FUNCTION IN NORMOTENSIVES AND ESSENTIAL HYPERTENSIVES

It has been suggested that hyperinsulinemia compensating insulin resis tance in glucose metabolism may be a pathogenic factor in essential hy pertension. On the other hand, age-associated increases in the prevale nce of glucose intolerance and hypertension are also well established. The aim of this study is to clarify the influence of aging on insulin sensitivity in glucose metabolism and on renal sodium handling under hyperinsulinemia, which may relate to high blood pressure in insulin-r esistant subjects. Fifty-two normotensive subjects and 61 patients wit h essential hypertension were evaluated in this study. The subjects of these groups were divided into young (<40 years old) and middle-elder ly (greater than or equal to 40 years old): young normotensives (Y-NT, n = 22); middle-elderly normotensives (ME- NT, n : = 30); young hyper tensives (Y-HT, n = 9); and middle-elderly hypertensives (ME-HT, n = 5 2). Using the euglycemic hyperinsulinemic glucose clamp, insulin sensi tivity was assessed as M. value. Just before the start and the termina tion of the glucose clamp, creatinine clearance (Ccr) and urinary excr etion of sodium (UNaV) were measured. In addition, renal plasma now as sessed as para-aminohippuric acid clearance was also measured at the s ame time in several subjects; 8 Y-NT, 8 MF-NT, 3 Y-HT, and 10 ME-PIT. The M value was significantly lower in ME-NT, Y-HT, and ME-FIT, compar ed to Y-NT, although blood sugar and immunoreactive insulin levels wer e similar in all four groups. In normotensive subjects, there was a si gnificant negative correlation between age and M value. However, this correlation was not observed in hypertensive patients. UNaV decreased in MF-NT, Y-HT, and ME-PIT, but not in Y-NT under hyperinsulinemia by the glucose clamp, whereas Ccr showed no significant change in any gro up. In all subjects, the change of UNaV (Delta UNaV) correlated signif icantly and positively with the M value. Renal plasma now significantl y increased under hyperinsulinemia by the glucose clamp in only Y-HT, but not in the other groups. There was a significant, positive correla tion between Delta UNaV and the change of renal plasma now under hyper insulinemia by the glucose clamp. These results suggested that both th e impairments of the insulin sensitivity and insulin-induced vasodilat ion at the renal artery with aging may partially contribute to age-rel ated elevation of blood pressure through renal sodium retention by com pensating hyperinsulinemia. On the other hand, it seems reasonable to assume that these abnormalities, which can contribute to high blood pr essure in essential hypertension, already may exist at lower ages in e ssential hypertensive patients. Am J Hypertens 1998;11:1056-1064 (C) 1 998 American Journal of Hypertension, Ltd.