The effect of peroxisome proliferator-activated receptor gamma (PPARγ) as a mediator of dietary fatty acids and thiazolidinedione in pulmonary arterial hypertension induced by cold stress of broilers.

The objective of this experiment was to evaluate the effects of dietary fish oil and pioglitazone as peroxisome proliferators-activated receptor gamma (PPARγ) activating ligands on the reduction of cold-induced ascites in broiler chickens. A total of 480 one-day-old (Ross 308) male chicks were randomly allocated to four treatment groups with eight replicates of 15 birds each. The following treatments were used: 1) ambient temperature (negative control), with basal diet; 2) cold-induced ascites (positive control), with basal diet; 3) cold-induced ascites, with basal diet +10 mg/kg/day pioglitazone and 4) cold-induced ascites, with basal diet +1% of fish oil. When compared with the positive control, body weight gain was higher (P ≤ 0.05) for broilers fed diets containing fish oil and pioglitazone at 28, 42, and 0-42 d. Broilers under cold-induced ascites had the highest blood pressure at 21 and 42 d, while fish oil and pioglitazone treatment reduced the blood pressure (P ≤ 0.05). Red blood cells, white blood cells, hematocrit, erythrocyte osmotic fragility, bursa of Fabricius and spleen weights were improved (P ≤ 0.05) for chickens fed fish oil diets and pioglitazone compared to the cold-induced ascites (positive control). Exposure to cold temperature resulted in an increase in plasma T3 and T3/T4 ratio and decline in plasma T4 (P ≤ 0.05). In conclusion, PPARγ agonist pioglitazone and fish oil as source of omega-3 polyunsaturated fatty acid could be used as a strategy to reduce the negative effects of pulmonary arterial hypertension and ascites in broiler chickens.

Hypoxia induces an increase in intestinal permeability and pulmonary arterial pressures in neonatal Holstein calves despite feeding the flavonoid rutin.

The purposes of this study were to determine whether the naturally occurring flavonoid quercetin, as its glucorhamnoside rutin, reduces intestinal permeability and susceptibility to hypoxia-induced pulmonary hypertension in neonatal Holstein calves. A 2 × 2 between-subjects factorial design was conducted using Holstein steers (n = 16). Factors included oxygen level (simulated altitude of 4,572 m vs. 975 m) and quercetin supplementation as its glucorhamnoside rutin (4 g of quercetin per day vs. 0 g per day). Two days after arrival (d 0 of study) the calves were blocked by body mass into treatment groups, and treatments were initiated. Pulmonary arterial pressure, echocardiography, and serum concentrations of orally administered lactulose (0.45 g/kg) and mannitol (0.15 g/kg) were measured on d 12, 13, and 14, respectively. Calves were euthanized on d 15 and pulmonary tissues collected for semiquantitative scoring of histological lesions. Data were analyzed using linear regression, generalized estimating equations, and 2-sample proportion tests. Hypoxia, but not rutin, was found to be associated with intestinal permeability. The lactulose-mannitol ratio was 0.54 ± 0.13 (standard error) in hypoxic calves and 0.02 ± 0.13 in normoxic controls. Hypoxia increased mean pulmonary arterial pressure. Calves fed rutin under hypoxic conditions tended to have a lower mean pulmonary arterial pressure (59 ± 7 mmHg) than control calves (80 ± 7 mmHg) but similar pressures under normoxic conditions. Paradoxically, however, a greater proportion of calves fed rutin had histological evidence of pulmonary arteriolar medial hypertrophy and adventitial hyperplasia than did controls. In conclusion, the findings of this study indicate that hypoxia increased intestinal permeability in neonatal calves. The flavonoid quercetin, as its glucorhamnoside rutin, had no protective effect on intestinal permeability, and, although it tended to reduce the severity of hypoxia-induced pulmonary hypertension, a greater proportion of calves fed rutin had histological lesions consistent with pulmonary arteriolar remodeling.

Calcium-Sensing Receptor Arbitrates Hypoxia-Induced Proliferation of Pulmonary Artery Smooth Muscle Cells via the G Protein-PLC-IP3 Pathway.

Pulmonary arterial hypertension (PAH), also known as broilers ascites syndrome, is characterized by hypoxia, pulmonary artery pressure, and right heart failure. However, less information is available about the molecular mechanisms of PAH. We evaluated the mediation of calcium-sensing receptor by inducing hypoxia for the possible proliferation of pulmonary artery smooth muscle cells via the G protein pathway. For this purpose, we used an in vitro trial of chicken cell culture and confirmed our results by using immunohistochemistry, immunofluorescence staining, quantitative real-time polymerase chain reaction assay, and Western blotting analysis. Our results showed that the mRNA and protein expression levels of calcium-sensing receptor (CaSR) were significantly upregulated in cells when co-incubated with CaCl2. However, the levels of mRNA and protein were obviously decreased when supplemented with blocking agents (NiCl2, 2-APB, and D609). Furthermore, the experimentally induced hypoxia also upregulated the expression of CaSR gene as compared to CaSR gene expression in control cells. Together, these results indicate that hypoxia plays an important role in the expression of CaSR gene in pulmonary artery smooth muscle cells and reveals new targets for the CaSR excited hypothesis to prevent and control PAH in chickens.