Oxidative stress and endothelial dysfunction in pulmonary arteries of aged rats.
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 gp91(phox) (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.
Podlutsky
Andrej
A
Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Ballabh
Praveen
P
Csiszar
Anna
A
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D000109:Acetylcholine