Nitric oxide deficiency in chronic kidney disease

Abstract

The overall production of nitric oxide (NO) is decreased in chronic kidney disease (CKD) which contributes to cardiovascular events and further progression of kidney damage. There are many likely causes of NO deficiency in CKD and the areas surveyed in this review are: 1. Limitations on substrate (l-Arginine) availability, probably due to impaired renal l-Arginine biosynthesis, decreased transport of l-Arginine into endothelial cells and possible competition between NOS and competing metabolic pathways, such as arginase. 2. Increased circulating levels of endogenous NO synthase (NOS) inhibitors, in particular asymmetric dimethylarginine (ADMA). Increased methylation of proteins and their subsequent breakdown to release free ADMA may contribute but the major culprit is probably reduced ADMA catabolism by the enzymes dimethylarginine dimethylaminohydrolases. 3. Reduced renal cortex abundance of the neuronal NOS (nNOS)α protein correlates with injury while increasing nNOSβ abundance may provide a compensatory, protective response. Interventions that can restore NO production by targeting these various pathways are likely to reduce the cardiovascular complications of CKD as well as slowing the rate of progression.

Ethnicity-specific differences in L-arginine status in South African men

“…48 Our analysis supports this observation by revealing a negative association of L-arginine with serum urea in Caucasian but not African men. The differences in L-arginine metabolism between these groups warrant tentative speculation on potential contributing factors in the light of relevant studies by other researchers.…”

“…L-arginine has been reported to enhance kidney function, including the excretion of urea, via the generation of NO. 48 This is supported by our observation in Caucasian males of a significant negative linear relationship (single and partial correlations) of urea with L-arginine. In contrast, a weaker association of L-arginine with ADMA (partial regression) in African men, compared with that in Caucasians, and no significant association with SDMA may indicate a reduced regulation of NO production in these Africans.…”

Apparent Treatment-Resistant Hypertension and Chronic Kidney Disease: Another Cardiovascular-Renal Syndrome?

“…49 Patients with CKD are also known to have reduced NO bioavailability as a result of inflammation, oxidative stress, and uremic toxins. 50 Because NO is responsible for tonic inhibition of the SNS, NO deficiency is thought to cause sympathetic overactivity and increased asymmetric dimethylarginine in patients with CKD, thus potentially contributing to hypertension. Notably, asymmetric dimethylarginine levels correlate with plasma norepinephrine levels, left ventricular hypertrophy, and left ventricular dysfunction.…”

“…Notably, asymmetric dimethylarginine levels correlate with plasma norepinephrine levels, left ventricular hypertrophy, and left ventricular dysfunction. 50 Thus, over time, multiple mechanisms of chronic SNS stimulation play a role in the development of hypertension.…”

Nitric oxide releasing-dendrimers: an overview

“…Due to the properties outlined above, an exogenous NO deliver is a potential therapeutic agent, inasmuch deficiencies in NO biosynthesis are related to some diseases (Baylis, 2008;Luiking, Engelen, Deutz, 2010). NO can be administered in gaseous form (respiratory route) in specific cases (Serafim et al, 2012), but this compound is known to react with a wide number of molecules (proteins, thiols, heme proteins, metals and others) and also can be oxidized in solution to NO 2 by O 2 (Fukuto et al, 2012;Toledo, Augusto, 2012).…”