Insulin, Prostaglandins, and the Pathogenesis of Hypertension

Hypertension is associated with hyperinsulinemia in the presence or absence of obesity or glucose intolerance. Physiological concentrations of insulin decrease the catecholamine-induced production of prostaglandin I₂ (PGI₂; prostacyclin) and PGE₂, two potent vasodilators, in adipose tissue, one of the largest organs in the body. This finding suggests that hyperinsulinemia increases peripheral vascular resistance and blood pressure by inhibiting the stimulatory effect of adrenergic agonists (and perhaps other agonists) on the production of PGI₂ and PGE₂ in adipose tissue (and perhaps other tissues). This concept is supported by evidence that PGI₂ and PGE₂ modulate vascular reactivity in states of health and disease. For example, during insulin deficiency, i.e., in diabetic ketoacidosis, PGI₂ and PGE₂ production by adipose tissue are increased, and peripheral vascular resistance and blood pressure are decreased. This hypothesis is also supported by evidence that blood flow through rat and human adipose tissue is decreased in obesity and that insulin decreases the blood flow through adipose tissue in nonobese rats. Thus, insulin may regulate PGI₂ and PGE₂ production by adipose tissue (and possibly other tissues) through a wide range of concentrations with important physiological and clinical consequences.