INSULIN-RESISTANCE, HYPERINSULINEMIA AND HYPERTENSION

Association between insulin resistance and hypertension: Insulin resis tance and reactive hyperinsulinemia occur not only with obesity, impai red glucose tolerance or non-insulin-dependent (type 2) diabetes melli tus, but also in many non-obese, non-diabetic patients with essential hypertension and their currently normotensive, lean young offspring an d in some other conditions known to promote hypertension. Insulin resi stance impairs glucose tolerance, while insulin resistance and/or hype rinsulinemia promote dyslipidemia, body fat deposition and probably at herogenesis. Therefore, the common coexistence of a genetic predisposi tion for hypertension with insulin resistance helps to explain the fre quent, although temporally often dissociated, occurrence of hypertensi on as well as dyslipidemia, obesity and type 2 diabetes in a given sub ject. Pathogenetic mechanisms: In the pathogenesis of hypertension, in appropriate vasoconstriction (due to dysbalance of vasoactive substanc es and/or raised cytosolic Ca2+) and/or a structural vasculopathy is a very important ultimate causative event. In the presumed mosaic of pa rticipating presser mechanisms, distinct Na+ retention is almost oblig atory with diabetes mellitus, while essential and particularly obesity -associated hypertension probably involves a tendency for sympathetic activation. Development of insulin resistance: Insulin resistance may develop as a consequence of an intracellular excess of Ca2+ or decreas e in Mg2+, an impaired insulin-mediated rise in skeletal muscle blood flow, increased sympathetic activity or being overweight. Acute hyperi nsulinemia on the one hand causes arterial vasodilation and on the oth er hand enhances renal sodium reabsorption and sympathetic activity. C hronically, hyperinsulinemia may promote cardiovascular muscle cell pr oliferation and atherogenesis, and it has been proposed that insulin r esistance in certain transmembranous cation exchange systems may eleva te cytosolic Ca2+. Nevertheless, whether insulin resistance and/or hyp erinsulinemia itself contribute to the pathogenesis of hypertension is still unclear.