Postdoctoral Research Fellow
Dept. of Health and Human Physiology
Training Mentor: Gary L. Pierce, MD
email: seth-holwerda@uiowa.edu
Research Project
Role of sympathetic nerve activation on vascular function in humans with Moderate/High Anxiety
Anxiety disorders are the most common mental health problems in the US, and are independently related to increased cardiovascular disease risk. Study aims: 1) determine the extent to which elevated sympathetic nerve activity (microneurography) and altered autonomic function (e.g., baroreflex) is associated with reduced vascular function (e.g., inflammation, stiffness) in adults with high compared with low levels of anxiety, and 2) determine the extent to which a validated anxiety-lowering therapy can lower sympathetic nerve activity and arterial stiffness and lead to improvement in autonomic function in individuals with moderate/high anxiety. The overall hypothesis is that high levels of anxiety promote elevations in sympathetic nerve activity and contributes to vascular inflammation, impaired large elastic artery function, and impaired cardiac baroreflex sensitivity. Current efforts also include the examination of the potential interaction between anxiety and obesity because obese individuals are more likely to suffer from anxiety and depression and exhibit elevations in systemic inflammation. Studies are ongoing. We hypothesize that having a lean rather than obese phenotype may be protective to an extent against anxiety-related changes in autonomic and vascular function.
Acute increases in sympathetic nerve activity, such as during mental stress, can lead to transiently greater large elastic artery stiffness. Also, in healthy humans, acute mental stress induces transient endothelial dysfunction, an important modulator of arterial stiffness. In addition to studies described above, we are also investigating whether greater cardiovascular risk in individuals with high anxiety is related to augmented vasoconstrictor responses to sympathoexcitation. These studies include simultaneous recordings of muscle sympathetic nerve activity (microneurography) and brachial artery blood flow calculated from artery diameter and blood velocity (Doppler ultrasound) during stress (mental math or cold pressor test).
Elevated sympathetic nerve activity mediates increases in large central elastic artery stiffness independent of changes in blood pressure in humans
Evidence suggests that elevated sympathetic nerve activity may contribute to increase large central elastic artery stiffness (i.e., carotid, aorta), a robust independent predictor of cardiovascular disease. However, experimental manipulations involving increased (e.g., handgrip exercise) or decreased (e.g., ganglionic blockade) sympathetic nerve activity in humans also evoke concomitant changes in arterial blood pressure making interpretation difficult. We are focused on whether acute and/or chronic elevations in muscle sympathetic nerve activity increase central artery stiffness independent of blood pressure in humans. We assess carotid and aortic stiffness and muscle sympathetic nerve activity (microneurography) at baseline and during lower body negative pressure, a stimulus known to cause cardiopulmonary baroreceptor-mediated increases in muscle sympathetic nerve activity without major changes in blood pressure. The relative changes muscle sympathetic nerve activity and carotid and aortic stiffness during lower body negative pressure are being examined to determine whether sympathetic nerve activity can directly mediate increases in large central elastic artery stiffness. Using a cross-sectional approach in a larger sample of healthy participants, we are also determining the extent to which resting muscle sympathetic nerve activity is related to large central elastic artery stiffness. Studies are ongoing. We hypothesize that lower tonic levels of resting muscle sympathetic nerve activity are associated with preserved carotid and aortic function.