Insulin resistance--not hyperinsulinemia--is pathogenic in essential hypertension.

A correlation between essential hypertension and insulin resistance/hyperinsulinemia is well documented, and there is adequate reason to believe that this association is causal. The common presumption that hyperinsulinemia mediates this connection is based on studies demonstrating various pressor effects of insulin, such as sodium retention, activation of the sympathetic nervous system, and stimulation of renin output. However, a consideration of physiological parameters in essential hypertensives indicates that these insulin-mediated pressor effects are unlikely to play a crucial pathogenic role in most cases of essential hypertension. Moreover, physiological elevation of insulin following a meal is typically associated with a reduction of blood pressure in hypertensives and the elderly. Euglycemic insulin clamps tend to reduce blood pressure in elderly subjects, and prolonged maintenance of hyperinsulinemia in animals does not raise blood pressure. In fact, insulin has long been known to have direct vasodilatory or antipressor effects on resistance vessels, and there is recent evidence that insulin reduces vascular resistance in skeletal muscles to facilitate glycogen storage after a meal. I propose that essential hypertensives experience a net deficit of insulin activity in vascular muscle, and that, in conjunction with other genetic or acquired defects of electrolyte transport, this leads to an increase in basal vascular tone and a hypersensitivity to pressor agents. Correction of insulin resistance usually aids blood pressure control, and in addition may mitigate the excess cardiovascular risk associated with hypertension.