Insulin, nitric oxide and the sympathetic nervous system: at the crossroads of metabolic and cardiovascular regulation

Epidemiological studies demonstrate an association between insulin resistan ce, hypertension and cardiovascular morbidity, Over the past decade, eviden ce has accumulated indicating that short-term insulin administration, in ad dition to its metabolic effects, also has important cardiovascular actions. The sympathetic nervous system and the L-arginine-nitric oxide pathway hav e emerged as central players in the mediation of insulin's cardiovascular a ctions. The underlying mechanisms and the factors that may govern the inter action between insulin and these two major cardiovascular regulatory system s have been studied extensively in healthy people and insulin-resistant sub jects, Here we summarize the current understanding and gaps in knowledge on insulin's cardiovascular actions in humans, and discuss possible pathophys iological consequences of their alteration. Based on recent new insight, we propose that a genetic and/or acquired defect of nitric oxide synthesis co uld represent a central defect triggering many of the metabolic, vascular a nd sympathetic abnormalities characteristic of insulin-resistant states, al l of which may predispose to cardiovascular disease. (C) Lippincott William s & Wilkins.