The antinatriuretic effect of insulin: An unappreciated mechanism for hypertension associated with insulin resistance?

Insulin resistance is proposed to be causally related to the metabolic syndrome disorders, but a direct cause-and-effect relationship between insulin resistance and hypertension was not originally obvious. Previous data suggested that insulin promotes sodium retention from the kidney, and thus research efforts focused on this action among several other possible pathways connecting insulin resistance and hyperinsulinemia with hypertension. A review of numerous studies provides evidence that this antinatriuretic effect of insulin is preserved in states of metabolic insulin resistance, representing a major mechanism for blood pressure elevation. More recent experimental and clinical studies have added data about the exact tubular sites of this insulin action, its relation with the respective insulin action on potassium handling, its possible role in the development of salt sensitivity in essential hypertension, as well as the involvement of oxidant stress in these associations. This review summarizes the current state of knowledge in this area and attempts to highlight an important but rather overlooked pathway for hypertension development in the metabolic syndrome, the influence of high insulin levels leading to volume expansion. Copyright (c) 2007 S. Karger AG, Basel.