Our findings suggest that PAR-2 is important in the regulation of blood pressure in vivo. A functional upregulation of PAR-2 by LPS was demonstrated by the activity of concentrations of PAR-2AP that were inactive in normal animals. We conclude that PAR-2 may play an important role in the hypotension associated with endotoxic shock and may represent a new therapeutic target.
Oxidative response regulates many physiological response in human health, but if not properly regulated it could also lead to a number of deleterious effects. The importance of oxidative stress injury depends on the molecular target, the severity of the stress, and the mechanism by which the oxidative stress is imposed: it has been implicated in several diseases including cancer, neurodegenerative diseases, malaria, rheumatoid arthritis and cardiovascular and kidney disease. Most of the common diseases, such as hypertension, atherosclerosis, heart failure, and renal dysfunction, are associated with vascular functional and structural alterations including endothelial dysfunction, altered contractility, and vascular remodeling. Common to these processes is increased bioavailability of reactive oxygen species (ROS), decreased nitric oxide (NO) levels, and reduced antioxidant capacity. Oxidative processes are up-regulated also in patients with chronic renal failure (CRF) and seem to be a cause of elevated risk of morbidity and mortality in these patients. In this review, we highlight the role of oxidative stress in cardiovascular and renal disease.
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.
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