Effects of novel therapies for pulmonary arterial hypertension - do they exert the effect we think they do?

Pulmonary arterial hypertension (PAH), i.e. high blood pressure in the lung, is a lethal condition. Novel therapies have shown promising pressure-lowering results, but their exact effects are unknown. In particular, one of the new drugs has been observed to induce symptoms similar to the ones of a genetic disorder, hereditary hemorrhagic telangiectasia (HHT). Patients with HHT can develop larger connections (shunts) between arteries and veins in the lung. If the same happens in PAH patients treated with the drugs, intrapulmonary shunts could explain the pressure-lowering effect; however, they might also dangerously lower the oxygen level if they become significant. Our goal is to map the microscopic 3D effects of two novel PAH therapies (in rat models), and to compare their effects with the vascular changes seen in human HHT and mouse models of HHT. Our results will lead to a better understanding of these novel PAH drugs, which is of great importance for the safety of patients.