Abstract
BackgroundEndothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances. The endothelium ability to produce nitric oxide is one of the most crucial mechanisms in regulating vascular tone. An increase in inducible nitric oxide synthase contributes to endothelial dysfunction in overweight persons, while oxidative stress contributes to the conversion of nitric oxide to peroxynitrite (measured as nitrotyrosine in vivo) in underweight persons. The objective of this study was to elucidate the interaction of body composition and oxidative stress on vascular function and peroxynitrite. This was done through an experimental design with three weight groups (underweight, normal weight and overweight), with four treatment arms in each. Plasma nitrotyrosine levels were measured 15–20 h post lipopolysaccharide (LPS) treatment, as were aortic ring tension changes. Acetylcholine (ACh) and sodium nitroprusside (SNP) challenges were used to observe endothelial-dependent and endothelial-independent vascular relaxation after pre-constriction of aortic rings with phenylephrine.ResultsNitrotyrosine levels in saline-treated rats were similar among the weight groups. There was a significant increase in nitrotyrosine levels between saline-treated rats and those treated with the highest lipopolysaccharide doses in each of the weight groups. In response to ACh challenge, Rmax (percentage reduction in aortic tension) was lowest in overweight rats (112%). In response to SNP, there was an insignificantly lower Rmax in the underweight rats (106%) compared to the normal weight rats (112%). Overweight rats had a significant decrease in Rmax (83%) in response to SNP, signifying involvement of a more chronic process in tension reduction changes. A lower Rmax accompanied an increase in peroxynitrite after acetylcholine challenge in all weight groups.ConclusionsEndothelial dysfunction, observed as an impairment in the ability to reduce tension, is associated with increased plasma peroxynitrite levels across the spectrum of body mass. In higher-BMI rats, an additional role is played by vascular smooth muscle in the causation of endothelial dysfunction.
Highlights
Endothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances
The normal function of the endothelium depends on the balance of these factors, and a mechanism leading to endothelial dysfunction is reduced production of nitric oxide
After treatment with ACh, the underweight rat aortic rings had an Percentage reduction in aortic tension (Rmax) of 137%, and in the normal weight group, an Rmax of 121% was observed (P = 0.03)
Summary
Endothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances. The objective of this study was to elucidate the interaction of body composition and oxidative stress on vascular function and peroxynitrite. This was done through an experimental design with three weight groups (underweight, normal weight and overweight), with four treatment arms in each. The normal function of the endothelium depends on the balance of these factors, and a mechanism leading to endothelial dysfunction is reduced production of nitric oxide. In certain disease states, such as HIV infection, atherosclerosis and other inflammatory conditions [7], there is an increase in oxidative stress This results from a disturbance in the balance between the production of reactive oxygen species (free radicals) and antioxidant defences. O2- non-enzymatically reacts with nitric oxide to produce peroxynitrite, a highly aggressive oxidant [1, 8]
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