Silpa Chinnakotla
Pronouns:
Research Mentor(s): Patrick Robichaud
Research Mentor School/College/Department: Internal Medicine – Cardiology Research / Medicine
Program: UROP
Session: Session 5 (2:40pm – 3:30pm)
Authors: Silpa Chinnakotla, Patrick Robichaud
Abstract
This study looks to explore the underlying mechanisms of the diuretic spironolactone to treat patients with pulmonary arterial hypertension (PAH). PAH is a rare and often idiopathic condition that primarily affects women, and a highly effective treatment is yet to be discovered. This study was done using a SUGEN-hypoxia (SuHx) rat model, which is a method of using growth factor receptor agonist Sugen 5416 and hypoxia conditions to induce PAH into rats. The PAH results in phenotypes similar to those in humans diagnosed with PAH. To complete this study, four different experiments were completed: (1) the right ventricular systolic pressure and pulmonary arterial pressure were taken for SuHx rats and non-SuHx rats with and without spironolactone treatment, (2) human pulmonary arterial cell cultures, blood samples, and tissue samples were analyzed using PCR and an ATP assay, and (3) a an analysis of lung histology of the rat models. Throughout all of these experiments, we also use different amounts of spironolactone to determine the appropriate dosage. Our analysis reveals that spironolactone treatment will result in a mean arterial pressure and blood tests in SuHx rats at near-normal levels while having no negative effect on the rats without SuHx treatment. We also determined how spironolactone impacts ATP production and purinergic signaling, or the binding of purine compounds (such as ATP) to pulmonary arterial cell membranes to change cell proliferation rates. In addition, we determined how six different target genes are impacted as a result of these changes in purinergic signaling pathways. Lastly, we visualized amounts of inflammation in pulmonary arteries within the rat lung samples from rats treated with and without spironolactone. With these results, it is possible to further describe the mechanism by which spironolactone works to reduce PAH complications.
