Oxidative stress and endothelial dysfunction in pulmonary arteries of aged rats

Andrej Podlutsky, Praveen Ballabh, Anna Csiszar

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Aging in the systemic circulation is associated with generalized endothelial dysfunction and increased oxidative stress, which are thought to contribute to the increased morbidity and mortality of cardiovascular diseases in the elderly. Previous studies have shown that pulmonary artery pressure and vascular resistance increase with normal aging in humans, yet age-related functional and phenotypic changes in the pulmonary arteries have not been characterized. To determine whether in the pulmonary circulation aging elicits endothelial dysfunction and oxidative stress, isolated pulmonary arteries of young (3 mo old) and aged (28 mo old) F344 rats were compared. We found that aging in rat pulmonary arteries is associated with impaired acetylcholine- induced relaxation and vascular oxidative stress [assessed by dihydroethidine and 5 (and 6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate-acetyl ester fluorescence assays]. Endothelial dysfunction in the aged pulmonary vessels is reversed by the inhibition of NAD(P)H oxidase. The expressions of gp91phox (both mRNA and protein), NAD(P)H oxidase isoform type 1 (Nox-1; mRNA), and Nox-4 (mRNA) tend to increase in aged vessels; however, only changes in Nox-4 reached statistical significance. In pulmonary arteries of aged rats, the protein expression of endothelial nitric oxide synthase, Cu,Zn-SOD, Mn-SOD, and glutathione peroxidase is unaltered, whereas the expression of catalase is significantly decreased. Our results suggest that aging is associated with oxidative stress and endothelial dysfunction in the pulmonary arteries, which may contribute to the age-related functional alterations in the pulmonary circulation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume298
Issue number2
DOIs
StatePublished - 2010
Externally publishedYes

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Pulmonary Artery
Oxidative Stress
Pulmonary Circulation
NADPH Oxidase
manganese peroxidase
Messenger RNA
Nitric Oxide Synthase Type III
Inbred F344 Rats
Glutathione Peroxidase
Vascular Resistance
Catalase
Acetylcholine
Superoxide Dismutase
Blood Vessels
Protein Isoforms
Esters
Proteins
Cardiovascular Diseases
Fluorescence
Morbidity

Keywords

  • Free radical
  • Lung
  • Pulmonary circulation
  • Reactive oxygen species
  • Senescence

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Oxidative stress and endothelial dysfunction in pulmonary arteries of aged rats. / Podlutsky, Andrej; Ballabh, Praveen; Csiszar, Anna.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 298, No. 2, 2010.

Research output: Contribution to journalArticle

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