PDE5A x SERT

We previously reported a study on 288 broiler (Gallus gallus) chicks who received caffeine in water between days 3 and 42, at levels of 0, 6.25, 12.5, 25, 50 and 100 mg/kg body weight (BW)/day. In the previous report, we found that caffeine caused pulmonary hypertension (PH)-associated mortality in a significant minority (20%-30%) of birds, including right ventricular hypertrophy and ascites. We have also shown a significant upregulation of the serotonin transporter (SERT), troponin T2, adenosine A₁ receptor (ADORA1) and phosphodiesterase 5A (PDE5) in chicken suffering from PH. Here, we examine the resistant (survived) chicks from the first study that had not died due to acute heart failure and did not have clinical signs of pulmonary hypertension. Our goal was to determine whether birds who lacked overt signs of disease had subclinical manifestations, including similar changes in gene expression, growth rates and altered systemic haemodynamics. We found that growth was significantly increased by caffeine consumption (p < 0.01) at low doses; however, dosage over 50 mg/BW/d had remarkable adverse effects on growth (p < 0.01). Blood pressure, troponin T2 and PDE5 gene expression were not significantly altered by caffeine administration (p > 0.05). However, SERT gene expression linearly increased with increasing caffeine dosage (p < 0.01). The impact of caffeine on ADORA1 gene expression was dose dependent and nonlinear. In conclusion, despite the significant effects of caffeine on birds' growth, no significant negative effects of caffeine were observed on the cardiovascular function of resistant chickens. This work provides valuable information for further study on different dosage of caffeine in an animal model.

Pulmonary hypertension (PH), remains a challenging disease with a large impact on both humans and meat-type chickens. PH is characterized by the onset of idiopathic pulmonary arterial hypertension leading to right ventricular failure. In this experiment relative gene expression of adenosine A₁ receptor (ADORA1), serotonin transporter (SERT), phosphodiesterase 5A (PDE5) and troponin T2 were compared in hearts from broilers with acute right ventricular failure and from healthy birds. There were major increases in adenosine A₁ receptor (177%) and serotonin transporter (475%), and more modest but significant increases in PDE5 (146%) and troponin T2 (140%) gene expressions in broilers with right ventricular failure compared to healthy birds (P<0.01). This novel report shows that pulmonary hypertension related gene expression in broilers is similar to that in humans. This molecular similarity between PH in broilers and human patients suggests, first, that they will make a suitable animal model for study PH in humans, but also that the literature on PH in humans may be profitably applied to the study of PH in broilers.