Obesity-associated hypertension: Hyperinsulinemia and renal mechanisms

Hyperinsulinemia and insulin resistance have been postulated to link obesity and hypertension. Evidence supporting this concept derives mainly from epidemiologkal studies showing a correlation between insulin resistance, hyperinsulinemia, and blood pressure and from short-term studies suggesting that insulin has renal and cardiovascular actions that, if sustained, could elevate blood pressure. However, a cause-and-effect relation between insulin and hypertension has not been clearly established. Recent studies indicate that chronic hyperinsulinemia, similar to that found in obese hypertensive patients, did not raise blood pressure in normal dogs, even when renal excretory capability was reduced by prior removal of kidney mass. Chronic insulin infusion also failed to elevate blood pressure in dogs maintained on a high sodium intake and did not potentiate the long-term blood pressure responses to angjotensin II or norepinephrine. The presence or absence of insulin resistance may not be a major factor in determining the blood pressure response to hyperinsulinemia since chronic insulin infusion also failed to cause hypertension in obese, insulin-resistant dogs. Although hyperinsulinemia causes transient sodium retention, sustained decreases in renal excretory capability sufficient to cause chronic hypertension did not occur in dogs. In rats, insulin infusion causes small increases in blood pressure, although several characteristics of the hypertension (e.g., salt-sensitivity) differ from those observed in obese human hypertensive patients. Whether humans more closely resemble dogs or rats with respect to their longterm cardiovascular responses to insulin remains to be determined. However, very high insulin levels in humans with insulinoma do not cause hypertension, and several studies suggest that there is only a weak correlation between plasma insulin concentration and blood pressure in normal humans. Therefore, additional factors besides hyperinsulinemia per se may be responsible for a major component of obesity-associated hypertension.