Background: Pulmonary hypertension is a deadly and debilitating disease characterized by high blood pressure in the pulmonary vasculature. Patients who suffer from pulmonary hypertension experience reduced exercise capacity, fatigue and shortness of breath. Advances in diagnosis and treatment of pulmonary hypertension have been made but many patients still suffer from idiopathic pulmonary hypertension. Previously, we created a miR-200b knockout mouse and determined that these mice have pulmonary hypertension. We also determined that miR-200b could regulate the expression of endothelin receptor A which is known to play a role in vasoconstriction in the lungs. I hypothesized that the endothelin family is involved in the development of pulmonary hypertension observed in miR-200b KO mice.

Methods: To determine the role of endothelin signalling in miR-200b KO mice we treated mice with an endothelin receptor antagonist, bosentan, for three weeks. Pulmonary hypertension was evaluated using echocardiography and graded maximal exercise tests were conducted on a metabolic treadmill to evaluate exercise ability.

Results: Echocardiography measurements of pulmonary acceleration time (PAT) and PAT/pulmonary ejection (PET) time improved in miR-200b KO mice after three weeks of treatment (p=0.4777 and 0.5136 respectively). Bosentan treated miR-200b KO mice also showed no difference in PAT or PAT/PET comparted to WT mice after three weeks of treatment (p=0.9985 and 0.7398 respectively). Bosentan treated miR-200b KO mice also increased their run time by an average of 110 seconds after three weeks of treatment.

Conclusion: Bosentan treated miR-200b KO mice showed reduced pulmonary hypertension and increased exercise ability after three weeks of treatment with bosentan, an endothelin receptor antagonist. This suggests that decreases in miR-200b could lead to dysregulation of the endothelin family and the development of pulmonary hypertension.