Endothelial dysfunction and body mass index: is there a role for plasma peroxynitrite?

Theresa Chikopela; Douglas C Heimburger; Longa Kaluba; Pharaoh Hamambulu; Newton Simfukwe; Wilbroad Mutale; John R Koethe; Fastone Goma

doi:10.1186/s43088-020-00092-6

Endothelial dysfunction and body mass index: is there a role for plasma peroxynitrite?

Beni Suef Univ J Basic Appl Sci. 2021;10(1):4. doi: 10.1186/s43088-020-00092-6. Epub 2021 Jan 14.

Authors

Theresa Chikopela¹, Douglas C Heimburger^{2

3}, Longa Kaluba⁴, Pharaoh Hamambulu¹, Newton Simfukwe⁵, Wilbroad Mutale⁶, John R Koethe⁷, Fastone Goma⁵

Affiliations

¹ Department of Human Physiology, Faculty of Medicine, Lusaka Apex Medical University, Lusaka, Zambia.
² Vanderbilt Institute for Global Health and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
³ Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia.
⁴ School of Medicine, Cavendish University, Lusaka, Zambia.
⁵ Department of Physiological Sciences, School of Medicine, University of Zambia, Lusaka, Zambia.
⁶ Department of Health Policy and Management, School of Public Health, University of Zambia, Lusaka, Zambia.
⁷ Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA.

Abstract

Background: Endothelial 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 in underweight persons, oxidative stress contributes to the conversion of nitric oxide to peroxynitrite (measured as nitrotyrosine in vivo). 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 hours post lipopolysaccharide (LPS) treatment, as were aortic ring tension changes. Acetylcholine (ACh) and sodium nitroprusside (SNP) challenges were used to observe endothelial dependent and independent vascular relaxation after pre-constriction of aortic rings with phenylephrine.

Results: Nitrotyrosine 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, R_max (percentage reduction in aortic tension) was lowest in overweight rats (112%). In response to SNP, there was an insignificantly lower R_max in the underweight (106%) compared to the normal weight (112%). Overweight rats had a significant decrease in R_max (83%) in response to SNP, signifying involvement of a more chronic process in tension reduction changes. A lower R_max accompanied an increase in peroxynitrite after acetylcholine challenge in all weight-groups.

Conclusions: Endothelial 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.

Keywords: body mass index; endothelial dysfunction; endothelial-dependent vascular relaxation; nitrotyrosine; peroxynitrite.

Abstract

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