INTERACTIONS BETWEEN INSULIN AND SODIUM HOMEOSTASIS IN ESSENTIAL-HYPERTENSION

It has been proposed, therefore, that hyperinsulinemia may favor the d evelopment of hypertension through sodium retention, sympathetic nervo us system activation, and vascular hypertrophy. In insulin-resistant h ypertensive subjects, insulin infusion during euglycemic clamp promote s a transient sodium retention by stimulating proximal tubular Na+ rea bsorption, but chronic hypertension usually is not associated with ext racellular fluid and plasma volume expansion. In essential hypertensiv e subjects, intracellular potassium is decreased and intracellular sod ium increased, which is consistent with insulin resistance. The latter is also associated with high red blood cell Li+/Na+ exchange, and chr onic insulin treatment in insulin-dependent diabetics induces a slight increase in Li+/Na+ CT. This is a functioning mode of the Na+/H+ exch ange, and its increase may reflect either an increased number of trans port units or abnormal kinetic properties, Experiments in vitro and in vivo suggested that any change in insulin concentration and insulin s ensitivity may affect Li+/Na+ and Na+/H+ countertransport. High Li+/Na + and Na+/H+ CT are associated with a significant cardiac and vascular remodeling in essential hypertension, insulin-dependent diabetes, and familiar hypertrophic cardiomyopathy. Reduced insulin sensitivity is associated with salt-sensitive hypertension. Finally, insulin potentia tes the effects of other agonists (eg, thromboxane A2, angiotensin II) on vascular contraction and cell growth. These data indicate that ins ulin may play a role in the pathogenesis of hypertension and its major complications by amplifying the effects of sodium, vasoconstrictors, and growth factors.