The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine

Abstract

Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA) ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS) and thereby nitric oxide (NO), respectively. Methods: Rabbits were fed either an arginine diet (group A, n = 9), standard rabbit chow plus atorvastatin (group S, n = 8), standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8) or standard rabbit chow (group C, n = 9) as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. Results: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. Discussion: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques.

SGLT2 inhibition with empagliflozin improves coronary microvascular function and cardiac contractility in prediabetic ob/ob−/− mice

“…The main site of action of SGLT2 inhibitors is the kidney, and the extent of the pleiotropic effects that this class of drugs have been still unknown. It is known that l -arginine is a physiological precursor to the formation of NO in endothelium-dependent vasodilation; and NO has several intracellular effects that lead to vasorelaxation, endothelial regeneration, inhibition of leukocyte chemotaxis, and platelet adhesion [62]. In the ob/ob −/− mice, decreased cardiac NO production and increased oxidative stress have previously been demonstrated [63].…”

Acute cocoa Flavanols intake has minimal effects on exercise-induced oxidative stress and nitric oxide production in healthy cyclists: a randomized controlled trial

“…As intracellular ADMA and arginine compete for NOS binding, ADMA and arginine levels regulate NO production [ 33 ]. In addition, extracellular ADMA and arginine also compete for cell transport (CAT-2) [ 34 ]. Thus, the higher the arginine/ADMA-ratio, the more arginine may be expected to be available as a substrate for eNOS to produce NO.…”

Circulating Concentrations of Key Regulators of Nitric Oxide Production in Undernourished Sheep Carrying Single and Multiple Fetuses

“…For example, in humans, high ADMA concentrations have been consistently shown to correlate with cardiovascular diseases and preeclampsia [4]. The L-arginine to ADMA ratio can thus be used to assess altered NOS activity due to alterations of this axis [5].…”