In:
American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 295, No. 5 ( 2008-11), p. L756-L766
Kurzfassung:
Cardiac defects associated with increased pulmonary blood flow result in pulmonary vascular dysfunction that may relate to a decrease in bioavailable nitric oxide (NO). An 8-mm graft (shunt) was placed between the aorta and pulmonary artery in 30 late gestation fetal lambs; 27 fetal lambs underwent a sham procedure. Hemodynamic responses to ACh (1 μg/kg) and inhaled NO (40 ppm) were assessed at 2, 4, and 8 wk of age. Lung tissue nitric oxide synthase (NOS) activity, endothelial NOS (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), and heat shock protein 90 (HSP90), lung tissue and plasma nitrate and nitrite (NO x ), and lung tissue superoxide anion and nitrated eNOS levels were determined. In shunted lambs, ACh decreased pulmonary artery pressure at 2 wk ( P 〈 0.05) but not at 4 and 8 wk. Inhaled NO decreased pulmonary artery pressure at each age ( P 〈 0.05). In control lambs, ACh and inhaled NO decreased pulmonary artery pressure at each age ( P 〈 0.05). Total NOS activity did not change from 2 to 8 wk in control lambs but increased in shunted lambs (ANOVA, P 〈 0.05). Conversely, NO x levels relative to NOS activity were lower in shunted lambs than controls at 4 and 8 wk ( P 〈 0.05). eNOS protein levels were greater in shunted lambs than controls at 4 wk of age ( P 〈 0.05). Superoxide levels increased from 2 to 8 wk in control and shunted lambs (ANOVA, P 〈 0.05) and were greater in shunted lambs than controls at all ages ( P 〈 0.05). Nitrated eNOS levels were greater in shunted lambs than controls at each age ( P 〈 0.05). We conclude that increased pulmonary blood flow results in progressive impairment of basal and agonist-induced NOS function, in part secondary to oxidative stress that decreases bioavailable NO.
Materialart:
Online-Ressource
ISSN:
1040-0605
,
1522-1504
DOI:
10.1152/ajplung.00146.2007
Sprache:
Englisch
Verlag:
American Physiological Society
Publikationsdatum:
2008
ZDB Id:
1477300-4
SSG:
12
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