Last Friday, Mark Bilodeau, a fifth year PhD candidate in the Program in Experimental and Molecular Medicine (PEMM), presented his future research on a possible contributor to hypertension in people suffering from chronic heart failure. Hypertension contributes to hypertrophy of the left ventricle and progression of the disease in heart failure patients. Bilodeau is studying a component of the blood pressure regulation pathway called the Mas receptor, which is present on specialized cells called astrocytes in the brain stem. Bilodeau explained that current treatment for heart failure patients with hypertension is focused on treating the effects of elevated sympathetic activity, rather than on cutting off stimulation of the sympathetic nervous system at its source: the brain stem.
The Mas receptor is important because it is considered a potential “choke point” for sympathetic activation. A small peptide called ANG 1-7 is known to bind to the Mas receptor. Moreover, previous studies have indicated that ANG 1-7 increases blood pressure when it is introduced into the rostral ventrolateral medulla (RVLM), a portion of the brain stem involved in propagating the sympathetic nervous response as it flows down the spine and diverges to the rest of the body.
Bilodeau plans to investigate sympathetic tone and blood pressure in a mouse model for heart failure in which Mas receptor expression has been knocked down in the astrocytes of the RVLM. He hypothesizes that the absence of the Mas receptor will prevent overstimulation of the sympathetic nervous system by ANG 1-7. Bilodeau has created an experimental setup to study the sympathetic response, which includes a viral based delivery to knockdown the Mas receptor. He described going on what he termed a “fishing expedition” to locate the RVLM for injections. Using the neurotransmitter glutamate, a known sympathetic stimulator, as “bait,” Bilodeau will probe the brain until he sees a sympathetic response to know he is in the right spot. Bilodea and his advisor, Jay Leiter, a physiology professor at Dartmouth’s medical school look forward to the exciting potential of these experiments to change the direction of treatment for patients suffering from chronic heart failure.
