Electronic Thesis and Dissertation Repository


Master of Science


Physiology and Pharmacology


Gros, Robert


Cardiovascular disease is one of the leading causes of death in Canada. Treatment currently focuses on preventing the increase of sympathetic signaling seen in heart failure. However, it has recently been noted that cardiac function is dependent on parasympathetic tone. Previous studies have demonstrated the development of heart failure when cholinergic targets are knocked out in cardiomyocytes. Transgenic mouse models that have increased cholinergic transmission show protection against cardiovascular insults. We have shown that transgenic mice overexpressing vesicular acetylcholine transporter in cholinergic cells show cardiovascular protection in response to ex vivo insults. As well, this protection is seen when cholinergic signaling was increased using acetylcholinesterase inhibition. Moreover, although no differences on cardiovascular parameters were seen in response to in vivo acetylcholinesterase inhibition alone, it was found to re-establish hemodynamic parameters and prevent cardiac hypertrophy and fibrosis in response to a hyper-sympathetic mouse model. In conclusion, increasing cholinergic transmission provides protection against cardiovascular insults.