Exploring the Relationship Between Muscle Sympathetic Nerve Activity and Endothelial Function in Heart Failure with Reduced Ejection Fraction

Kanokwan Bunsawat; Stephen Ratchford; Jeremy Alpenglow; Jarred Iacovelli; Josef Stehlik; D. Walter Wray

doi:10.1152/physiol.2025.40.S1.0178

Abstract only Background: The sympathetic nervous system (SNS) and endothelial function are thought to contribute to cardiovascular homeostasis in an inverse, reciprocal manner, such that elevations in SNS activity are accompanied by attenuated endothelium-dependent vasodilation. Patients with heart failure with reduced ejection fraction (HFrEF) represent a clinical population that is characterized by both SNS overactivation and decrements in vascular function, though the relationship between these aspects of HFrEF pathophysiology has not been examined. Thus, the purpose of the present study was to determine the relationship between gold-standard assessments of SNS activity (microneurography) and endothelial function (flow-mediated vasodilation, FMD) in patients with HFrEF. We hypothesized that an inverse relationship would be evident, such that patients with the highest resting SNS activity would demonstrate the lowest %FMD values. Methods: To test this hypothesis, NYHA Class II and III patients with HFrEF ( n = 15, 70 ± 8 years, 29.0 ± 3.5 kg/m 2 ) underwent assessments of resting muscle sympathetic nerve activity (MSNA) and brachial artery FMD testing. MSNA was quantified as burst frequency (bursts/min) and burst incidence (bursts/100 heartbeats). FMD was quantified as the peak change in vessel diameter following cuff release and was expressed as a percentage increase from pre-occlusion values (%FMD) and as %FMD normalized for shear rate area-under-the-curve (s -1 ; %FMD/SR). Simple linear regression was performed to explore the relationship between MSNA and FMD. Data were reported as mean ± standard deviation. Results: Resting MSNA burst frequency and burst incidence were 42 ± 9 bursts/min (range: 31 - 62 bursts/min) and 65 ± 16 bursts/100 heartbeats (range: 42 - 94 bursts/100 heartbeats), respectively. %FMD and %FMD/SR were 3.4 ± 1.1% (range: 1.5 - 5.8%) and 0.10 ± 0.03 a.u. (range: 0.06 - 0.16 a.u.). MSNA burst frequency was not related to %FMD ( r = 0.-45, slope = -0.054, p = 0.095) but was inversely related to %FMD/SR ( r = 0.-58, slope = -0.002, p = 0.022). MSNA burst incidence was not related to %FMD ( r = 0.-49, slope = -0.033, p = 0.066) but was inversely related to %FMD/SR ( r = 0.-55, slope = -0.001, p = 0.036). Conclusion: These initial data partially support our hypothesis that disease-related elevations in SNS activity are accompanied by lower endothelial function in patients with HFrEF. Interestingly, the relationship between the SNS and endothelial function became more apparent when shear rate was taken into consideration. This distinction is important, as the increase in brachial artery shear rate is the physiological stimulus for endothelium-dependent vasodilation during the FMD test. Taken together, these initial data demonstrate, for the first time, the relationship between the SNS and endothelial function in patients with HFrEF and highlight the potential for designing an intervention that targets both pathways to better improve the treatment of HFrEF. The National Institutes of Health (HL118313, D.W.W.) and the U.S. Department of Veterans Affairs (I01RX001311, D.W.W.; IK2RX003670, to K.B.). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Exploring the Relationship Between Muscle Sympathetic Nerve Activity and Endothelial Function in Heart Failure with Reduced Ejection Fraction

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