UC Davis

Hypertension is considered to be the largest modifiable risk factor for cardiovascular disease. Even with the longstanding recognition of hypertension as a disease, there is still poor understanding of the observable differences in men and women responses to antihypertensive agents. The necessity of treating hypertension to prevent premature death has led to the urgent need to develop new approaches for revealing sex-specific mechanisms of hypertension and predicting how drugs will alter vascular function. The smooth muscle cells that line the walls of small resistance arteries and arterioles have been the subject of investigation for decades due to their important role in regulating blood flow and blood pressure. This dissertation focuses on formulating an in silico model of the vascular smooth muscle cell incorporating new electrophysiological and Ca2+ signaling data suggesting key sex-specific differences in male and female arterial myocytes. The model highlights the importance of sex-specific differences in Cav1.2 and Kv2.1 channels. The Cav1.2 and Kv2.1 channels have previously been associated with remodeling in the pathogenesis of hypertension and model predictions described herein also suggest differential responses to antihypertensive agents. The work covered in this dissertation provides insights into sex-specific differences in arterial smooth muscle cell physiology and has the potential to expand our understanding for how sex-dependent differences in the expression, spatial organization, and function of key important ion channels are involved in the regulation of vascular smooth muscle.