It has been proposed, therefore, that hyperinsulinemia may favor the development of hypertension through sodium retention, sympathetic nervous system activation, and vascular hypertrophy. In insulin-resistant hypertensive subjects, insulin infusion during euglycemic clamp promotes a transient sodium retention by stimulating proximal tubular Na+ reabsorption, but chronic hypertension usually is not associated with extracellular fluid and plasma volume expansion. In essential hypertensive subjects, intracellular potassium is decreased and intracellular sodium increased, which is consistent with insulin resistance. The latter is also associated with high red blood cell Li+/Na+ exchange, and chronic insulin treatment in insulin-dependent diabetics induces a slight increase in Li+/Na+ CT. This is a functioning mode of the Na+/H+ exchange, and its increase may reflect either an increased number of transport units or abnormal kinetic properties. Experiments in vitro and in vivo suggested that any change in insulin concentration and insulin sensitivity may affect Li+/Na+ and Na+/H+ counter-transport. 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 potentiates the effects of other agonists (eg, thromboxane A2, angiotensin II) on vascular contraction and cell growth. These data indicate that insulin may play a role in the pathogenesis of hypertension and its major complications by amplifying the effects of sodium, vasoconstrictors, and growth factors.