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Loss of Bioavailable NO with Enhanced iNOS Expression and Oxidative Stress Increase Pulmonary Arteriolar Tone in Aged Mice
Author(s) -
Drinovac Robert,
Jagadapillai Rekha,
Gozal Evelyne,
Lin Xingyu,
Vaishnav Radhika,
Friedland Robert P.,
Roberts Andrew M.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.728.5
Subject(s) - oxidative stress , lung , endothelial dysfunction , nitric oxide , medicine , nitric oxide synthase , hypoxic pulmonary vasoconstriction , microcirculation , pulmonary hypertension , endocrinology , vasoconstriction , pathology
Aging impairs blood vessel function and leads to cardiovascular disease. Vascular dysregulation with aging, caused by endothelial dysfunction in numerous vascular beds, has been reported as a consequence of decreased bioavailable nitric oxide (NO). However, the effect of endothelial dysfunction with aging on pulmonary microcirculation is not well characterized. We hypothesized that aging causes pulmonary microvascular dysfunction by decreasing lung NO bioavailability, resulting in the constriction of pulmonary arterioles. To determine if decreased NO bioavailability in the lung, as occurs in aging, affects pulmonary vascular function, we assessed the effect of aging on pulmonary arteriolar responses in C57BL/6J mice (11–32 months old). Pulmonary microvascular diameters (ranging from 25–54 μm) were examined in the right lungs of anesthetized mice with open chest by intra‐vital microscopy before and after the nitric oxide synthase (NOS) inhibitor, L‐NAME, was administered (0.1mg/g body wt) to produce acute NOS inhibition. Pulmonary arteriolar tone in the older mice (> 2 years 4 months) did not significantly increase (1.4 ± 2.8%, mean ± S.D, n=4) after L‐NAME treatment, suggesting that NO synthesis is decreased in aging mice. In contrast, in the younger mice (≤ 2 years 4 months), pulmonary arteriolar tone increased by 11.5 ± 9.4% (n=4, P < 0.05) after L‐NAME. Expression of inducible NOS (iNOS) and TNF‐α in lung tissue increased with the age of the mice indicating a greater level of oxidative stress and inflammation. These results suggest that, with aging, a loss in the bioavailability of NO and increased oxidative stress could impair the lung's ability to maintain a low microvascular resistance, which could affect alveolar perfusion.