l-Arginine and its metabolites in kidney and cardiovascular disease

Abstract

L-Arginine is a semi essential amino acid synthesised from glutamine, glutamate and proline via the intestinal-renal axis in humans and most mammals. L-Arginine degradation occurs via multiple pathways initiated by arginase, nitric-oxide synthase, Arg: glycine amidinotransferase, and Arg decarboxylase. These pathways produce nitric oxide, polyamines, proline, glutamate, creatine and agmatine with each having enormous biological importance. Several disease are associated to an L-arginine impaired levels and/or to its metabolites: in particular various L-arginine metabolites may participate in pathogenesis of kidney and cardiovascular disease. L-Arginine and its metabolites may constitute both a marker of pathology progression both the rationale for manipulating L-arginine metabolism as a strategy to ameliorate these disease. A large number of studies have been performed in experimental models of kidney disease with sometimes conflicting results, which underlie the complexity of Arg metabolism and our incomplete knowledge of all the mechanisms involved. Moreover several lines of evidence demonstrate the role of L-arg metabolites in cardiovascular disease and that L-arg administration role in reversing endothelial dysfunction, which is the leading cause of cardiovascular diseases, such as hypertension and atherosclerosis. This review will discuss the implication of the mains L-arginine metabolites and L-arginine-derived guanidine compounds in kidney and cardiovascular disease considering the more recent literature in the field.

Inflammation and Oxidative Stress in Chronic Kidney Disease—Potential Therapeutic Role of Minerals, Vitamins and Plant-Derived Metabolites

“…High levels of metabolic end-products-the uremic toxins-have become clinically relevant in CKD progression and are tightly related to many CKD-associated complications [5][6][7][8][9][10][11]. CKD patients tend to suffer from many complications, such as hypertension, cardiovascular diseases, anemia, metabolic acidosis [12], altered immune response, mineral and bone disturbances and neurological complications [13].…”

l-Arginine Enhances Resistance against Oxidative Stress and Heat Stress in Caenorhabditis elegans

“…More recently, a growing interest has been focused on the natural antioxidant compounds present in plants, animals, and even microbes [5,6,7]. As a semi-essential amino acid, l -Arg is readily available from a variety of food sources and has many important functions in living organisms as well as in various diseases [8,9,10]. Since l -Arg is used as a biosynthetic precursor of nitric oxide (NO) in mammals, it has been extensively studied and used to develop a variety of bioactive compounds.…”

Former very preterm infants show alterations in plasma amino acid profiles at a preschool age

“…In Zucker diabetic fatty rats, a citrulline-rich diet and subsequent increased arginine availability ameliorated the phenotype of metabolic syndrome, thus suggesting a beneficial effect of relative citrulline-and argininemia (26). One of the quantitatively most relevant catabolic pathways of arginine is its metabolism to ornithine and urea via arginase (27). Interestingly, ornithine concentrations were significantly lower in VPI whereas urea levels did not significantly differ between groups (mean ± SD, term 23.…”

“…Articles 0.124, Mann-Whitney U-test, not shown). Ornithine can be further metabolized to polyamines (putrescine, spermidine, and spermine), which are involved in various cellular functions including cell proliferation and differentiation (27). Even though the catalyzing enzyme, ornithine decarboxylase, is rate-controlling for this step, also ornithine availability is considered a limiting factor (28).…”

“…Even though the catalyzing enzyme, ornithine decarboxylase, is rate-controlling for this step, also ornithine availability is considered a limiting factor (28). As deregulation of polyamine pathways has been implicated in various pathological conditions such as stroke, and recent data suggest cardioprotection by spermidine supplementation (27,29), longitudinal assessment of the relevance of this finding in regard to future cardiovascular health of VPI seems advisable. In addition, former VPI displayed elevated glutamine and diminished glutamate plasma concentrations.…”