Electronic Thesis and Dissertation Repository


Master of Science




Dr. J. Kevin Shoemaker


This study examined the cardiac and vasomotor responses to submaximal handgrip exercise and beta-adrenergic control in carriers (n = 6) and non-carriers (n = 4) of a genetic variant of adenylyl cyclase 6 (AC S674). Rhythmic handgrip contractions (1 minute bout; 2 second contraction-relaxation period) were performed at three different intensities (20, 40, and 60% of maximal voluntary contraction force) to test the vasodilatory response to exercise. Additionally, two 5 minute infusions of isoproterenol (0.01 and 0.02 µg·kg-1·min-1 diluted in 5% dextrose) and one 10 minute infusion of propranolol (0.1 mg·kg-1 diluted in 0.9% saline) were used to examine beta-adrenergic mediated cardiovascular responses. Ascending aorta and brachial artery mean blood flow velocities (pulsed Doppler ultrasound) and brachial artery blood pressure (Finometer) were continuously measured during handgrip and pharmacological protocols. Vascular mechanics of the forearm were calculated using a three-element lumped windkessel model. At baseline, AC S674 carriers have decreased systemic vascular conductance and forearm vascular bed compliance, as well as increased pulse pressure. However, AC S674 carriers did not exhibit altered cardiac or vasomotor control during handgrip exercise, isoproterenol infusion, or propranolol infusion. These results indicate that expression of the dysfunctional genetic variant AC S674 has profound effects on systemic hemodynamics at rest. Chronic elevation in vascular contractile state may result in vascular stiffening and enhanced pulse pressures with detrimental long-term consequences for cardiovascular health.