The Influence of Muscle Sympathetic Nerve Activity on Sympathetic Transduction in Humans

Journal Title
Journal ISSN
Volume Title
University of Guelph

Background: The sympathetic nervous system plays an integral role in blood pressure (BP) regulation, but the resting level of sympathetic outflow directed towards skeletal muscle is poorly related to resting BP. These findings suggest counterregulatory mechanisms that could mitigate the effects of elevated sympathetic outflow. Specifically, downregulation of adrenergic sensitivity has been proposed, though the relationship between sympathetic outflow and sympathetic neurovascular transduction remains poorly understood.
Purpose: This thesis examined the association between sympathetic outflow and sympathetic-BP transduction. The overarching hypothesis is that resting MSNA will be negatively associated with sympathetic-BP transduction due to methodological limitations of the signal-averaging technique, baroreflex mechanisms governing MSNA burst occurrence, and α-adrenoreceptor responsiveness. Methods: Heart rate, BP, and muscle sympathetic nerve activity (MSNA) were quantified using electrocardiography, finger photoplethysmography, and fibular nerve microneurography, respectively. Signal-averaging was used to track and calculate the peak rise in BP following an MSNA burst, and the nadir change in BP following non-burst cardiac cycles. Results: We observed moderate negative correlations between MSNA and sympathetic-BP transduction in a large sample of normotensive adults. Further, we developed a log-linear normalization approach to correct for MSNA during cross-sectional comparisons of sympathetic-BP transduction. In addition, the timing of MSNA burst occurrence relative to cyclic oscillations in BP appears to be a key determinant of the sympathetic-BP transduction, considering the paradoxical reductions in BP following MSNA bursts firing distinctly above the mean BP set-point. Reflex sympathoexcitation using baroreceptor unloading increased MSNA but not the proportion of MSNA bursts firing above the mean BP set-point, highlighting distinct differences between tonic vs. reflex sympathetic outflow on sympathetic-BP transduction. Lastly, applying findings to patients with treated HFrEF revealed that patients present with lower sympathetic-BP transduction compared to healthy controls. These findings persisted after employing the correction approach to control for differences in resting MSNA, and when comparing a subset of patients with similar resting activity. Conclusions: The negative association between sympathetic outflow and sympathetic-BP transduction was largely governed by the proportion of MSNA bursts firing above the mean BP set-point, highlighting baroreflex mechanisms contributing to the reductions in sympathetic-BP transduction in individuals with elevated sympathetic outflow.

Blood pressure, Sympathetic nervous system, Sympathetic transduction, Baroreflex, Microneurography
Nardone M, Incognito AV, Kathia MM, Omazic LJ, Lee JB, Teixeira AL, Xie S, Vianna LC, Millar PJ. Signal-averaged resting sympathetic transduction of blood pressure: is it time to account for prevailing muscle sympathetic burst frequency? Am J Physiol Regul Integr Comp Physiol. 2021. 321(3):R484-R494. doi: 10.1152/ajpregu.00131.2021.
Nardone M, Katerberg C, Incognito AV, Teixeira AL, Vianna LC, Millar PJ. Blood pressure oscillations impact signal-averaged sympathetic transduction of blood pressure: implications for the association with resting sympathetic outflow. Am J Physiol Heart Circ Physiol. 2021. 321(4):H798-H806. doi: 10.1152/ajpheart.00422.2021.
Nardone M, Katerberg C, Teixeira AL, Lee JB, Bommarito JC, Millar PJ. Sympathetic transduction of blood pressure during graded lower body negative pressure in young healthy adults. Am J Physiol Regul Integr Comp Physiol. 2022. 322(6):R620-R628.doi: 10.1152/ajpregu.00034.2022.
Nardone M, Notarius CF, Badrov MB, Millar PJ, Floras JS. Attenuated sympathetic blood pressure transduction in patients with treated heart failure with reduced ejection fraction. Hypertension. 2022. 79(12): 2764-2773. doi: 10.1161/HYPERTENSIONAHA.122.19850.