Experimental research Effect of experimentally induced metabolic acidosis on aortic endothelial permeability and serum nitric oxide concentration in normal and high-cholesterol fed rabbits

Abstract

IntroductionMetabolic acidosis is present in end stage renal disease. There is a link between enhanced endothelial permeability and accelerated atherosclerosis. In this study, we investigated the effect of experimentally induced metabolic acidosis on aortic endothelial permeability and serum nitric oxide (NO) concentration in normal and high-cholesterol fed rabbits.Material and methodsTwenty-four male rabbits were divided into four groups: normal, hypercholesterolemic, acidemic, and hypercholesterolemic plus acidemic. Acidosis and hypercholesterolemia were induced by drinking water containing ammonium chloride (NH4Cl), and cholesterol-rich animal chow (1%), respectively. After 6 weeks, blood samples were taken and endothelial permeability was measured using the Evans blue dye injection method.ResultsHypercholesterolemic animals had higher aortic endothelial permeability compared with normal groups (16.18 ±0.91 µg EB/g tissue vs. 12.89 ±0.66 µg EB/g tissue, p < 0.05). Acidosis significantly increased endothelial permeability in the normal group (17.10 ±0.56 µg/g tissue vs. 12.89 ± 0.66 µg/g tissue; p < 0.05) but did not further increase endothelial permeability in hypercholesterolemic animals (16.18 ±0.91 µg EB/g tissue vs. 17.29 ±0.46 µg EB/g tissue; p > 0.05). Serum total cholesterol, low density lipoprotein (LDL) and NO concentrations in hypercholesterolemic animals were significantly higher than the normal group and acidosis could not change them either in the normal or in the high-cholesterol diet group.ConclusionsAlterations of serum lipids and NO are not the main mechanism for accelerated atherosclerosis during metabolic acidosis. Acidosis increases aortic endothelial permeability at least in a normal diet which may be a possible mechanism for progression of atherosclerosis processes in end-stage renal disease.

Ameliorative effect of statin therapy on oxidative damage in heart tissue of hypercholesterolemic rabbits

“…In the present study, serum and tissue NO of the cholesterol-rich-diet group was higher than normal-diet groups, while NO was decreased in group 4. Hypercholesterolemic animals had higher serum NO compared with normal-diet animals, which supports the results of previous studies [22][23][24][25][26]. The novelty of the present study lies in the fact that increased NO production in circulating and heart tissue worsens atherogenic conditions.…”

“…Atorvastatin treatment caused a decrease in MDA, whereas the high-cholesterol diet increased MDA of blood and heart tissue in cholesterol-rich diet-induced rabbits. Hypercholesterolemic animals had higher serum NO compared with normal-diet animals, which supports the results of previous studies [22][23][24][25][26]. Hypercholesterolemia might be attributed to LPO and excessive MDA production has been associated with atherogenesis.…”

Hypoxia in atherosclerosis and inflammation

“…In fact, elevated blood lactate has recently been associated with increased carotid atherosclerotic wall thickness in humans, although this was partially related to insulin resistance [68]. As plaque and systemic acidification are proatherogenic [69,70], enhanced lactate due to increased glycolysis may contribute to atherogenesis.…”