The vascular effects of L-Arginine in humans. The role of endogenous insulin.

Abstract

This study aimed at evaluating whether increased availability of the natural precursor of nitric oxide, L -arginine, could influence systemic hemodynamic and rheologic parameters in humans and whether the effects of L -arginine are mediated by endogenous insulin. 10 healthy young subjects participated in the following studies: study I, infusion of L -arginine (1 g/min for 30 min); study II, infusion of L -arginine plus octreotide (25 g as i.v. bolus ϩ 0.5 g/min) to block endogenous insulin and glucagon secretion, plus replacement of basal insulin and glucagon; study III, infusion of L -arginine plus octreotide plus basal glucagon plus an insulin infusion designed to mimic the insulin response of study I. L -Arginine infusion significantly reduced systolic (11 Ϯ 3, mean Ϯ SE) and diastolic (8 Ϯ 2 mmHg, P Ͻ 0.001) blood pressure, platelet aggregation (20 Ϯ 4%), and blood viscosity (1.6 Ϯ 0.2 centipois, P Ͻ 0.01), and increased leg blood flow (97 Ϯ 16 ml/min), heart rate, and plasma catecholamine levels ( P Ͻ 0.01). In study II, plasma insulin levels remained suppressed at baseline; in this condition, the vascular responses to L -arginine were significantly reduced, except for plasma catecholamines which did not change significantly. In study III, the plasma insulin response to L -arginine was reestablished; this was associated with hemodynamic and rheologic changes following L -arginine not significantly different from those recorded in study I. These findings show that systemic infusion of L -arginine in healthy subjects induces vasodilation and inhibits platelet aggregation and blood viscosity. These effects are mediated, in part, by endogenous released insulin.

Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox

“…This term has been used to refer to situations in which exogenous L-arginine concentrations apparently determine the level of NO production even when intracellular levels of L-arginine are available in excess. Data supporting other explanations for this paradox have been put forward by other investigators (17,21,36,39). For example, Giugliano et al (39) demonstrated that i.v.…”

Antihypertensive effect of insulin via nitric oxide production in the Zucker diabetic fatty rat, an animal model for non-insulin-dependent diabetes mellitus

“…Insulin has vasodilative and hypotensive effects (3)(4)(5)(6)(7)(8)(9). It has been reported that hypertension was improved by insulin treatment in patients with DM (10)(11)(12).…”

l-Arginine: An Ultradian-Regulated Substrate Coupled With Insulin Oscillations in Healthy Volunteers

“…Over the past years, there has been considerable interest in the involvement of L-arginine in the release of insulin through NO pathways (4 -7,23), which may explain the hemodynamic and vascular effects of insulin (8,9). The coupling of L-arginine, insulin, and glucose in a rhythmic way sheds new light on this complex interplay that might be significant in pathological states.…”

“…One other putative mechanism is the formation of nitric oxide (NO) from Larginine by the action of NO synthase in pancreatic ␤-cells (4 -7). It has been reported that systemic infusion of Larginine induces vasodilation, inhibits platelet aggregation, and reduces blood viscosity and that these effects are mediated by NO release (8,9). Although there might be a dietary need for L-arginine, it is produced endogenously from the turnover of the urea cycle within the liver and via conversion of citrulline to arginine in the renal proximal tubule (10,11).…”