This summer, I received an American Physiological Society Short-Term Research Education Program to Increase Diversity in Health-Related Research (APS STRIDE) fellowship. This fellowship, funded by APS and a grant from the National Heart, Lung and Blood Institute, allowed me to do 10 weeks of research at the University of Missouri. I focused on how aldosterone can decrease adenosine-induced coronary vasodilation, an important cardioprotective mechanism. Aldosterone is a steroid hormone which is associated with activation of the renin-angiotensin-aldosterone system (RAAS) (Klabunde, 2016), and adenosine is an important compound which has numerous roles in the body. This concept becomes important during heart attacks when adenosine would ideally increase dilation (widening) of heart blood vessels to increase blood delivery to damaged areas (Chen et al., 2013). Increased RAAS activation increases levels of aldosterone which ultimately decreases this protective mechanism, and the infarcted areas do not receive the blood they need in order to be protected. I will be exploring how aldosterone performs this action and whether it acts on one of the two main adenosine receptors in question: A_2A and A_2B. Individuals with high RAAS activation have higher levels of plasma aldosterone as well as a higher risk for heart attack, so understanding this pathway can be beneficial for those individuals. I used mice as an animal model and I am hoping that a better understanding of this mechanism can help humans with heart damage.

We increased plasma aldosterone in the mice by implanting osmotic mini pumps that infused aldosterone over a course of 4 weeks. Afterwards, we dissected coronary artery rings and measured vasodilatory (vessel widening) responses to a few vasodilators and specific agonists of the A_2A and A_2B receptors. This was done by mounting the rings in a muscle force measuring machine (wire myograph) and collecting data on their isometric tension production. We followed up these experiments with PCR (Polymerase Chain Reaction used to amplify segments of DNA), DHE staining (Dihydroethidium used to detect reactive oxygen species), and western blotting (identification and measurement of proteins).

Spending the summer as a STRIDE fellow was a really amazing experience for me. I’ve always been very passionate and interested in research and this summer was a reaffirmation of that. I enjoyed being involved in the project and working as a part of a team. This fellowship was incredibly helpful because we were able to network with other fellows from all over the country. We also completed regular assignments that strengthened our critical thinking, writing, and communication skills. I express my sincerest thanks to APS and the Bender lab for this opportunity!

References

1. Chen, J. F., Eltzschig, H. K., & Fredholm, B. B. (2013, April). Adenosine receptors as drug targets–what are the challenges? Retrieved July 28, 2017, from https://www.ncbi.nlm.nih.gov/pubmed/2353593
2. Klabunde, R. E. (2016, December 8). Renin-Angiotensin-Aldosterone System. Retrieved July 28, 2017, from http://www.cvphysiology.com/Blood%20Pressure/BP015

Maloree Khan is a senior majoring in Biochemistry at the University of Missouri. She is a 2017 APS STRIDE fellow working in Dr. Shawn Bender’s Lab at the University of Missouri Department of Biomedical Sciences. Khan’s fellowship is funded by the APS and a grant from the National Heart, Lung and Blood Institute.