The correlation between mtROS formation and acetylcholine-dependent relaxation revealed that mitochondrial radical formation significantly contributes to age-dependent endothelial dysfunction.

No abstract

Chronic nitroglycerin treatment results in development of nitrate tolerance associated with endothelial dysfunction (ED). We sought to clarify how mitochondria- and NADPH oxidase (Nox)-derived reactive oxygen species (ROS) contribute to nitrate tolerance and nitroglycerin-induced ED. Nitrate tolerance was induced by nitroglycerin infusion in male Wistar rats (100 microg/h/4 day) and in C57/Bl6, p47(phox/) and gp91(phox/) mice (50 microg/h/4 day). Protein and mRNA expression of Nox subunits were unaltered by chronic nitroglycerin treatment. Oxidative stress was determined in vascular rings and mitochondrial fractions of nitroglycerin-treated animals by L-012 enhanced chemiluminescence, revealing a dominant role of mitochondria for nitrate tolerance development. Isometric tension studies revealed that genetic deletion or inhibition (apocynin, 0.35 mg/h/4 day) of Nox improved ED, whereas nitrate tolerance was unaltered. Vice versa, nitrate tolerance was attenuated by co-treatment with the respiratory chain complex I inhibitor rotenone (100 microg/h/4 day) or the mitochondrial permeability transition pore blocker cyclosporine A (50 microg/h/4 day). Both compounds improved ED, suggesting a link between mitochondrial and Nox-derived ROS. Mitochondrial respiratory chain-derived ROS are critical for the development of nitrate tolerance, whereas Nox-derived ROS mediate nitrate tolerance-associated ED. This suggests a crosstalk between mitochondrial and Nox-derived ROS with distinct mechanistic effects and sites for pharmacological intervention.

No abstract

1. Movement (frequency of changes) between inside and outside housing areas, time spent in each area, tonic immobility (TI) and differential blood cell counts were studied in relation to feather condition in laying hens of two genotypes, white (LSL) and brown (LT). 2. From 18 weeks of age, LSL and LT were kept in 4 groups of 50 birds in a poultry house with passages to a roofed scratching room and a grassland area with a stocking density of one bird/10 m2. 3. All birds had transponders to record the movements of each hen between inside and outside areas and the time spent in each area during 24 h. Feather scoring was carried out at 6 ages from 20 to 48 weeks. At 44 weeks of age, TI reactions of 40 hens (20 from each genotype) were quantified and blood smears from 20 hens (10 from each genotype) were analysed for differential leucocyte counts. 4. LSL hens moved more frequently to outdoor areas than LT hens (44.66 vs 28.78 least square/d). However, the proportion of time spent on grassland was greater in LT than in LSL hens, whereas time (%) spent by LT hens in the roofed scratching area was less than for LSI hens. 5. In LT hens TI was shorter while heterophil/lymphocyte ratio and basophilia were greater than in LSL hens. 6. Total body feather score was poorer in LSL than in LT hens. Incidence of footpad inflammation was higher in LSL than LT hens. 7. There was a positive association between TI and footpad inflammation. The percentage of time spent on grassland and feather damage were inversely correlated. 8. More movement between the areas, as in LSL hens, was positively associated with fearfulness, whereas long periods on grassland, as in LT hens, were associated with indicators of increased stress. The negative correlation between feather damage and time spent outside suggests that feather pecking risk decreases in birds attracted to grassland.