D. Walter Wray
· ProfessorVerifiedUniversity of Utah · Geriatrics
Active 1975–2026
About
D. Walter Wray, PhD, MSc, joined the Division of Geriatrics at the University of Utah as a Research Assistant Professor in 2008. He is a founding member of the Utah Vascular Research Laboratory, a consortium affiliated with the University of Utah and the Salt Lake City Veterans Administration Medical Center Geriatrics, Research, Education and Clinical Center. Dr. Wray maintains an active, extramurally-funded research program broadly focused on vascular and autonomic physiology, with an emphasis on aging and age-related diseases such as heart failure. His current projects include studies examining neurohumoral control of muscle blood flow at rest and during acute exercise, as well as investigations into the causes and consequences of chronic sympathoexcitation in heart failure. His research aims to understand the mechanisms underlying vascular dysfunction and autonomic regulation in aging and cardiovascular diseases, contributing valuable insights into potential therapeutic targets for these conditions.
Research topics
- Medicine
- Internal medicine
- Cardiology
Selected publications
American Journal of Physiology-Heart and Circulatory Physiology · 2026-01-30
articleOpen accessSenior authorWild-type transthyretin amyloidosis (wtATTR) is a unique cause of heart failure typically associated with orthostatic hypotension, likely implicating baroreflex dysfunction; however, this is yet to be investigated. Using the lower-body negative pressure technique to simulate orthostatic stress, we have identified impaired peripheral vascular responsiveness, which occurred in tandem with an inability to arterial blood pressure, suggesting that diminished sympathetic vasomotor responsiveness likely contributes to baroreflex dysfunction and impaired blood pressure regulation in patients with wtATTR.
Physiology · 2025-05-01
articleBackground: The subendocardial viability ratio (SEVR), derived from pulse wave analysis (PWA), provides a non-invasive estimate of myocardial perfusion. Lower SEVR predicts all-cause mortality in various patient populations including those with hypertension, type 2 diabetes mellitus and chronic kidney disease. Recent evidence indicates that SEVR is lower in patients with heart failure with preserved ejection fraction (HFpEF) and is influenced by several factors such as obesity, biological sex, and wave reflection parameters. Obesity is a prevalent comorbid condition associated with HFpEF-related pathophysiology, but its influence on SEVR in patients with HFpEF is unknown. Thus, the current study sought to examine the role of obesity on SEVR in patients with HFpEF, and to explore the impact of biological sex on this relationship. Methods: Twenty-seven (14M/13F, age 70±7 y, body mass index [BMI] 33±5 kg/m 2 ) patients with HFpEF underwent assessments of cardiovascular hemodynamics (PWA) and myocardial perfusion (SEVR). Results: Compared to males, females had higher supine brachial systolic blood pressure (SBP, 131±14 vs 120±8 mmHg), brachial pulse pressure (PP, 59±12 vs 48±8 mmHg), aortic (central) SBP (117±9 vs 109±7 mmHg), aortic PP (45±8 vs 37±7 mmHg), augmentation pressure (AP, 14±7 vs 9±5 mmHg), augmentation index normalized to heart rate of 75 bpm (AIxHR75, 26±10 vs 18±12 %), systolic pressure time integral (SPTI, 2,389±242 vs 2,113±206 mmHg.s.min), ejection duration (ED, 38±3 vs 35±3 %), forward (Pf, 31±7 vs 25±3 mmHg), and reflected (Pb, 19±3 vs 15±3 mmHg) pulse height and lower SEVR (126±16 vs 147±19 %) (all, p<0.05). Importantly, BMI was associated with SEVR (r = -0.48), SPTI (r = 0.42), ED (r = 0.39) and Pf (r = 0.34) (all, p<0.05) in the whole cohort. When data were examined by biological sex, BMI was associated with SEVR (r = -0.64) and SPTI (r = 0.52) (both, p<0.05) in females but not males (SEVR, r = -0.37; SPTI, r = 0.32, both, p>0.05) with HFpEF. Conclusion: These preliminary data provide novel insight into the influence of obesity on myocardial perfusion in adults with HFpEF in a sex-dependent manner. VA Advanced Fellowship in Geriatrics (N.A.C.) NIH (HL170007 & HL162856, D.W.W.) U.S Department of Veterans Affairs (CX002152, D.W.W; IK2RX003670, 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.
Circulation Heart Failure · 2025-04-24
articleSenior authorBACKGROUND: Peripheral microvascular dysfunction is a hallmark feature of both heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) pathophysiology, due partly to impairments in nitric oxide signaling secondary to tetrahydrobiopterin (BH 4 ) deficiency and oxidative stress. METHODS: Using a randomized, double-blind, placebo-controlled crossover design, this study examined the impact of enteral BH 4 (10 mg/kg), an antioxidant cocktail (AOx), and coadministration of these 2 agents (BH 4 +AOx) on microvascular function in patients with HFrEF (n=14, 64±10 years) and HFpEF (n=19, 74±9 years). Passive limb movement was utilized to assess locomotor muscle microvascular function, and biomarkers of inflammation and oxidative damage were measured. RESULTS: Compared with placebo, the peak change in leg blood flow was not statistically different after AOx administration (HFrEF, P =0.60; HFpEF, P =0.61), but improved following BH 4 ( P =0.033) and BH 4 +AOx ( P =0.019) in both HFrEF (placebo: 234±31; BH 4 : 357±45; BH 4 +AOx: 355±49 mL/min) and HFpEF (placebo: 269±33; BH 4 : 367±47; BH 4 +AOx: 394±65 mL/min). The total hyperemic response to passive limb movement (leg blood flow area under the curve) was not statistically different across treatments in patients with HFrEF ( P =0.29), but increased following BH 4 ( P =0.016) and BH 4 +AOx ( P =0.040) in the HFpEF group. CRP (C-reactive protein) was lower following BH 4 ( P =0.007) and BH 4 +AOx ( P =0.007) in HFpEF (placebo: 4268±547; BH 4 : 2721±391; BH 4 +AOx: 2779±376 ng/mL), but was not statistically different in HFrEF ( P =0.39). CONCLUSIONS: Together, these results provide new evidence for the efficacy of acute BH 4 administration to improve some aspects of locomotor muscle microvascular function in patients with HFrEF and HFpEF, with no apparent benefit of AOx administration, alone or in combination with BH 4 , in either group. These findings lend further conceptual support for the nitric oxide pathway as a modifiable target in the treatment of heart failure.
American Journal of Physiology-Heart and Circulatory Physiology · 2025-09-17 · 1 citations
editorialOpen accessPhysiological Reports · 2025-02-27 · 6 citations
articleOpen accessHeightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) is not fully understood. This study tested the hypothesis that elevated MSNA diminishes the vasodilatory response to PLM in healthy young males (n = 11, 25 ± 2 yr). Post exercise circulatory occlusion (PECO) following 2 min of isometric handgrip (HG) exercise performed at 25% (ExPECO 25%) and 40% (ExPECO 40%) maximum voluntary contraction was used to incrementally engage the metaboreceptors and augment MSNA. Control trials were performed without PECO (ExCON 25% and ExCON 40%) to account for changes due to HG exercise. PLM was performed 2 min after exercise and hemodynamics were assessed. MSNA was recorded by microneurography in the peroneal nerve (n = 8). Measures of MSNA (i.e., burst incidences) increased during ExPECO 25% (+15 ± 5 burst/100 bpm) and ExPECO 40% (+22 ± 4 burst/100 bpm) and returned to pre-HG levels during ExCON trials. Leg vascular conductance (vasodilation) during PLM was reduced by 16% and 44% during ExPECO 25% and ExPECO 40%, respectively. These findings indicate elevated MSNA attenuates the vasodilatory response to PLM and the magnitude of reduction in vasodilation during PLM is graded with the degree of sympathoexcitation.
Journal of Applied Physiology · 2025-08-21
reviewOpen accessHeart failure with preserved ejection fraction (HFpEF) is a complex multiorgan clinical syndrome representing ∼50% of all heart failure-related cases nationwide. HFpEF is more prevalent in women, yet both men and women with HFpEF present with distinct clinical phenotypes and prognosis that may be attributable, in part, to sex differences in anatomical, physiological, and/or hormonal characteristics. Of particular interest is the role of sex hormones, namely, estrogen, as a contributing factor to sex differences in vascular health in patients with HFpEF. This mini review provides a summary of recent evidence regarding sex differences in coronary microvascular function, peripheral vascular function, and central arterial stiffness in patients with HFpEF. Focus will also be given to potential mechanisms by which age-related loss of estrogen may alter these aspects of physiology in women with HFpEF and provide potential future directions related to implications for women's health in adults with HFpEF.
Physiology · 2025-05-01
articleSenior authorBackground: 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.
Physiology · 2025-05-01
articleSenior authorIntroduction: Post-traumatic stress disorder (PTSD) may increase the risk of cardiovascular disease (CVD). Greater levels of daily stress and exaggerated cardiovascular responses to stress with PTSD may contribute to high allostatic load, or the cumulative physiological effects accompanying chronic stress, and subsequently lead to elevated blood pressure and CVD. The purpose of this study was to compare levels of daily stress, systolic blood pressure (SBP) responses during acute stress, and 24-hour SBP values in PTSD and control (CON) subjects, and the relationships between these variables. We hypothesized greater levels of daily stress, SBP responses during acute stress and 24-hour SBP values in PTSD, as well as positive relationships between SBP responses during acute mental and physical stressors, levels of daily stress, and 24-hour SBP values. Methods: In PTSD ( n = 4, 31±8 yrs) and CON subjects ( n = 8, 34±7 yrs), we measured SBP changes (Δ; Finapres) during separate 3-minutes of mental arithmetic (MA) and static handgrip exercise (SHG) at 40% of their maximal voluntary contraction. Over 7-days, subjects kept a daily log of stressful events (DLSE). Last, subjects underwent ambulatory blood pressure monitoring (ABPM) for 24 hours. Group differences were assessed using unpaired t -tests and simple linear regression was performed to explore relationships between variables. Results: Peak ΔSBP was greater in PTSD compared to CON during MA (18±7 vs. 10±4, mmHg, P =0.03) and SHG (51±9 vs. 31±11 mmHg, P =0.01). In PTSD, compared to CON, there was a greater number of stressors/day (5±2 vs. 2±1, no., P <0.01), mean stressor severity (3±1 vs. 2±0, 1-5 scale, P <0.01), and sum stressor severity (SSS) over 7 days (104±37 vs. 31±16, a.u., P =0.01). 24-hr SBP and awake SBP were not different between groups (125±14 vs. 113±7, mmHg, P =0.06 and 125±13 vs. 118±8, mmHg; P =0.21, respectively), although asleep SBP was greater in PTSD compared to CON (112±10 vs. 101±7 mmHg, P =0.04). Amongst all subjects, no significant relationships existed between the peak ΔSBP during MA and ABPM or DLSE variables. No significant relationships existed between ΔSBP during SHG and ABPM variables. Significant relationships were noted between peak ΔSBP during SHG and SSS (R=0.60, P =0.05) and between SSS and 24-hr SBP (R=0.62, P =0.05) Conclusion: These data indicate peak ΔSBP during acute mental and physical stressors are exaggerated in PTSD. Along with greater levels of stress over a 7-day period, those with PTSD may experience higher SBP, particularly while asleep. Although a relationship existed between peak ΔSBP during SHG and SSS, as well as 24-hr SBP and SSS, these data do not clearly indicate significant relationships between ΔSBP during acute stress, DLSE and ABPM variables. In all, exaggerated ΔSBP during acute stress and elevated levels of daily stress may be important factors contributing to increased allostatic load and CVD risk, though further investigation is needed to clearly define these relationships. This project was funded by 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.
Dissecting the exercise pressor reflex in heart failure: A multi-step failure
Autonomic Neuroscience · 2025-03-13 · 2 citations
reviewOpen accessThe contribution of neural feedback originating from exercising limb muscles to the cardiovascular response to exercise was first recognized nearly 100 years ago. Today, it is well established that this influence is initiated by the activation of group III and IV sensory neurons with terminal endings located within contracting skeletal muscle. During exercise, these sensory neurons project feedback related to intramuscular mechanical and metabolic perturbations to medullary neural circuits which reflexively evoke decreases in parasympathetic and increases in sympathetic nervous system activity with the purpose of optimizing central and peripheral hemodynamics. Considerable evidence from animal and human studies suggests that the function of this regulatory control system, known as the exercise pressor reflex (EPR), is abnormal in heart failure and exaggerates sympatho-excitation which impairs the hemodynamic response to exercise and contributes to the functional limitations characterizing these patients. This review briefly introduces the key determinants of EPR control in health and covers the impact of heart failure on the integrity of each of its components and overall function. These include the sensitivity of group III/IV muscle afferents, afferent signal transmission in the spinal cord, and the central integration and processing of sensory feedback within the brainstem. Importantly, although most data relevant for this review come from studies in HFrEF, the limited HFpEF-specific insights are included when available. While arguably not part of the EPR, we also discuss the impact of heart failure on the exercise-induced increase of intramuscular stimuli of group III/IV muscle afferents and end-organ responsiveness to sympathetic/neurochemical stimulation.
Medicine & Science in Sports & Exercise · 2024-09-16
articleSenior authorINTRODUCTION: Patients with post-traumatic stress disorder (PTSD) have an increased risk of developing cardiovascular disease (CVD). The physiological underpinnings contributing to increased CVD risk with PTSD are poorly understood but may involve maladaptive changes in blood pressure regulation during stress. Elevated pressor responses during physical stress, such as exercise, often characterize populations with CVD and may predict future CVD in otherwise healthy adults. Some data suggests aberrant pressor responses during either acute physical or mental stress in PTSD, but evidence is limited, and it is unclear how pressor responses may manifest during combined stimuli. PURPOSE: To investigate pressor responses during acute physical and mental stress, alone and in combination, and to what extent these responses may be exaggerated in patients with PTSD compared to control (CON) subjects. METHODS: In patients with PTSD (n = 2, 34 ± 5 yrs) and CON subjects (n = 2, 33 ± 1 yrs) arterial blood pressure (Finapres) was determined at rest and during static handgrip exercise (SHG, 3 mins, 40% MVC), followed by post-exercise-circulatory-occlusion (PECO, 2 mins). Each condition (rest, SHG, PECO) was also performed with or without Mental arithmetic (MA). RESULTS: Resting mean arterial pressure (MAP) was greater in PTSD vs. CON (91 ± 4 vs. 75 ± 1 mmHg; P = 0.03). The average increase in mean arterial pressure (MAP) during MA was greater in PTSD vs. CON (8 ± 1 vs. 3 ± 1 mmHg; P = 0.03). The increase in MAP at the end of SHG was greater in PTSD vs. CON (44 ± 3 vs. 25 + 3 mmHg; P = 0.01). The increase in MAP during PECO was significantly greater in PTSD vs. CON (31 ± 2 vs. 16 ± 12 mmHg; P = 0.01). MA increased the MAP response during SHG in PTSD (3 ± 1 mmHg; P = 0.02), but not in CON (-2 ± 5 mmHg; P = 0.73). The MAP response during PECO was variably influenced by MA in PTSD and CON (4 ± 3 vs. 3 ± 7 mmHg; P = 0.11). CONCLUSIONS: These preliminary data suggest that pressor responses during acute physical (SHG, PECO) and mental (MA) stress are exaggerated in PTSD. Additionally, it appears that in PTSD, acute mental stress may further augment pressor responses to acute physical stress (SHG + MA). Taken together, these exaggerated pressor responses during acute physical and mental stress may represent a physiological maladaptation that could increase CVD risk in this patient group. Funded in part by grants from the U.S. Veterans Administration (CX002152) and the National Institutes of Health (HL162856)
Recent grants
Peripheral Vasoconstriction in Heart Failure: Mechanisms & Modulatory Influences
NIH · $1.9M · 2014–2020
Overcoming Exercise Intolerance in Veterans with Heart Failure: The Role of NO.
NIH · 2017–2021
Contribution of Endothelin-1 to Exercise Intolerance in HF
NIH · 2014–2016
Cardiovasomobility Research Training Program
NIH · $1.4M · 2018–2024
Frequent coauthors
- 543 shared
Russell S. Richardson
University of Utah
- 187 shared
Stephen J. Ives
Skidmore College
- 173 shared
Melissa A. H. Witman
University of Delaware
- 134 shared
Joel D. Trinity
University of Utah
- 114 shared
Zachary Barrett‐O’Keefe
Mayo Clinic in Arizona
- 113 shared
Stephen M. Ratchford
University of Utah
- 109 shared
John McDaniel
Kent State University
- 107 shared
Ryan S. Garten
Virginia Commonwealth University
Labs
Utah Vascular Research LaboratoryPI
Education
Ph.D., Internal Medicine
University of Utah
M.S., Internal Medicine
University of Utah
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