ATP and serotonin effects on vascular resistance and mitogenic pathways in broilers susceptible to idiopathic pulmonary arterial hypertensio

The purpose of this study was to determine the effects of a high tryptophan diet and the drugs serotonin (5-HT) and ATP on the pulmonary vasculature in broilers. Broilers were fed a high tryptophan (HT) diet (4X normal level of Trp = 0.88% by weight, n = 50) or a control diet (∼ 0.22% by weight, n = 50). Pulmonary arterial pressures and wedge pressures were measured by the advancement of a silastic catheter while recording using Acqknowledge software to determine broilers pulmonary vascular pressure profiles. The lungs were removed from euthanized broilers where the pulmonary artery (PA) and pulmonary 1A (P1A) and 2A (P2A) arterioles were prepared for wire myography. The drugs 5-HT (10-12 to 10-5M), ATP (10 -7 to 10-3M), 5-HT (10-10) + ATP (10 -7 to 10-3M), and acetylcholine (10-8 to 10-5M) were used to determine PA, P1A, and P2A response. Protein CREB activity was determined in the P1A (n = 3) by western blot protocol. Wedge pressure results demonstrated that broilers fed a HT diet had higher pulmonary arterial pressures than broilers fed a control diet, p < .05. Wire myography results demonstrated that P1A response to 5-HT + ATP was greater in broilers fed the HT than broilers fed a control diet, p < .05. The P1A and P2A showed a greater sensitivity to ATP only when compared to 5-HT + ATP in broilers fed the control diet, p < .05. Results demonstrated that the sensitivity to 5-HT was greater in the P1A compared to the P2A, p < .05. The P1A showed a greater increase in response to ATP as concentrations increased, p < .05. Western blot results showed that pCREB activity is present in the P1A of broilers. These results indicate that broilers fed a high tryptophan diet are more susceptible to idiopathic pulmonary arterial hypertension. The P1A is a greater contributor to vasoconstriction when 5-HT is present. 5-HT in the P1A and P2A of broilers fed a control diet attenuates ATP response.