About

Dr. Ryan M. Broxterman, Ph.D., is an Assistant Professor of Internal Medicine in the Division of Geriatrics and an Adjunct Assistant Professor in the Department of Nutrition & Integrative Physiology at the University of Utah. He is also a Research Health Scientist at the Salt Lake City Veterans Affairs Geriatric Research, Education, and Clinical Center. His research broadly focuses on the integration of vascular, metabolic, and neuromuscular function as determinants of health and physical function. This includes assessing vascular function, oxygen transport and utilization, exercise tolerance, and skeletal muscle bioenergetics in health and disease. Dr. Broxterman has published over 65 peer-reviewed papers in various scientific journals and maintains an extramurally-funded research program. His work aims to understand the physiological mechanisms underlying exercise capacity, vascular health, and aging, with particular attention to how these systems interact in different health conditions and in response to interventions such as exercise and dietary supplementation.

Research topics

• Medicine
• Cardiology
• Internal medicine
• Chemistry
• Endocrinology
• Anesthesia
• Biochemistry

Selected publications

• Age and sex shape plasma lipid associations to skeletal muscle mitochondrial respiration and H2O2 emission

  GeroScience · 2026-01-19

  article
  PublisherDOI

• Chamber oxygen concentration impacts mitochondrial function and hydrogen peroxide appearance in permeabilized human skeletal muscle fibers

  Biochimica et Biophysica Acta (BBA) - Bioenergetics · 2025-08-11 · 1 citations

  articleOpen accessSenior author

  Skeletal muscle mitochondrial respiration is commonly assessed ex vivo using permeabilized fibers in media with high oxygen (O 2 ) concentrations to ensure that O 2 availability does not limit respiration. However, high O 2 concentrations also increase the production of reactive O 2 species that can negatively affect respiration. In this study, we tested the hypotheses that permeabilized fiber mitochondria in a high, compared to low, O 2 concentration would (i) not be different at maximal state 3 respiration rate (V max ), (ii) have lower submaximal respiration rates at submaximal O 2 concentrations, and (iii) have greater total cumulative hydrogen peroxide (H 2 O 2 ) appearance. We continuously monitored mitochondrial state 3 respiration and H 2 O 2 appearance rates using high-resolution respirometry in permeabilized skeletal muscle fibers (12 untrained participants; 22 ± 4 yrs) with either control (~127 mmHg; CON) or high (~327 mmHg; HIGH) partial pressures of O 2 (PO 2 ). V max was not different between conditions (HIGH: 80.7 ± 16.7 vs. CON: 82.3 ± 18.7 pmol/s/mg, p = 0.695). The PO 2 at 80 % V max (P 80 ) was greater in HIGH (73.9 ± 25.5 vs. 28.0 ± 7.1 mmHg, p < 0.001) and respiration rates at 5–60 mmHg PO 2 were lower for HIGH than CON (all p < 0.001). Additionally, the total cumulative H 2 O 2 appearance was greater in HIGH than CON ( n = 11; 51.5 ± 23.2 vs. 18.3 ± 10.3 pmol/mg, p < 0.001), and this difference was directly correlated with the difference in P 80 ( r = 0.655, p = 0.029). The current findings support that a high O 2 concentration, by itself, does not appear to affect V max in the permeabilized skeletal muscle fiber preparation, but the corollary increase in H 2 O 2 exposure may diminish mitochondrial state 3 respiratory function. • High O 2 concentration does not appear to affect maximal state 3 respiration in the permeabilized skeletal muscle fibers. • High O 2 concentration does increase the total cumulative appearance of H 2 O 2 during the respiration protocol. • The increase in H 2 O 2 exposure from increased O 2 levels may diminish mitochondrial state 3 respiratory function over time.

  PublisherDOI

• Skeletal Muscle Fatigue in Rats Is More Consistently Related to Increased Inorganic Phosphate Concentration Than Acidosis

  Acta Physiologica · 2025-07-21 · 4 citations

  articleOpen accessSenior author

  AIM: Distinguish the relative importance of intramuscular acidosis (hydrogen ion) and inorganic phosphate in skeletal muscle fatigue in vivo in rats. METHODS: We used direct sciatic nerve electrical stimulations to evoke twitches at different frequencies of contraction (0.25-, 0.50-, 0.75-, 1-, 2-, and 4-Hz) in the triceps surae to impose a range of intramuscular metabolic perturbations, quantified by phosphorus nuclear magnetic resonance spectroscopy. Linear mixed-effects models were used to analyze the relationships between peak twitch force and intramuscular hydrogen ion or inorganic phosphate concentration (as Z-scores) during the protocols that decreased peak twitch force (2- and 4-Hz). RESULTS: Although intramuscular hydrogen ion and inorganic phosphate concentrations increased with increasing frequencies of contraction, peak twitch force did not begin to decrease until a "threshold" inorganic phosphate concentration was reached. A given hydrogen ion accumulation was associated with a greater decrease in peak twitch force during 4-Hz compared to 2-Hz (β: -1.19 vs. -0.62, p < 0.001). In contrast, the decrease in peak twitch force for a given inorganic phosphate accumulation was not different between 4- and 2-Hz (β: -0.89 vs. -0.85, p = 0.889). CONCLUSIONS: The inconsistent relationship between the decrease in twitch force and intramuscular hydrogen ion accumulation is not congruent with the primary mechanisms by which acidosis is thought to mediate muscle fatigue. In contrast, the discernible twitch force-inorganic phosphate breakpoint and the consistent relationship between the decrease in twitch force and intramuscular inorganic phosphate accumulation are congruent with the concept of a critical concentration beyond which inorganic phosphate mediates muscle fatigue.

  PublisherOA PDFDOI

• Evaluation of Endothelial-Mediated Mechanisms of Passive Leg Movement Hyperemia: Impact of Age and Exercise Training

  Physiology · 2025-05-01

  article

  The hyperemic response to passive leg movement (PLM) is largely (~80%) nitric oxide (NO) mediated in young adults, whereas both the overall response and NO contribution (~20%) are diminished in older adults. A transient hyperemic response remains in both groups after NO blockade, however, the mechanisms contributing to this remaining response are unknown. Vasodilatory substances including prostaglandins (PG) and endothelial derived hyperpolarizing factors (EDHF) are primary candidates contributing to PLM response. Moreover, these underlying mechanisms of the PLM response are likely influenced by exercise training in both young and older adults but this remains to be determined. Thus, we sought to determine if 1) PG and EDHF contribute to the hyperemic response in older adults, and 2) exercise training alters the mechanisms contributing to changes in PLM (i.e., NO, PG, or EDHF). The leg blood flow (LBF) response to PLM was measured by Doppler ultrasound in 9 young (25±4 yr) and 9 older (69±5 yr) adult males. PLM was performed with intra-arterial infusions of saline (control), N G -monomethyl-L-arginine (L-NMMA) to inhibit NOS and NO production, and a combination of L-NMMA, ketorolac tromethamine (KET) to inhibit cyclooxygenase and PG production, and fluconazole (FLUC) to inhibit cytochrome P-450 and EDHF (L-NMMA+KET+FLUC). This PLM and drug infusion protocol were repeated following 8 weeks of single leg knee-extension (KE) exercise training to determine if the vasodilatory mechanisms regulating PLM-induced hyperemia are altered by exercise training. The hyperemic response to PLM (total LBF area under the curve) was significantly attenuated from control with infusion of L-NMMA in young adults (-287±280 mL, p&lt;0.05) but remained unchanged in the older (-55±86 mL, P=0.70). Combined infusion of L-NMMA+KET+FLUC yielded similar results such that PLM decreased to the same degree as L-NMMA in young (-276±108 mL, p&lt;0.05) with no significant change in older adults (-116±81 mL, P=0.36). Following 8 weeks of single leg KE training, maximal power (KE max ) improved in both young (+33±13 W, p&lt;0.05) and older adults (+16±8 W, p&lt;0.05). Despite improvements in KE max , the hyperemic response to PLM only increased in young adults by ~30% (454±194 v. 604±351 mL, p&lt;0.05), while no improvement was observed in older adults (225±142 v. 236±89 mL, P=0.86). The contribution of NO to PLM did not change following exercise training in either young (-238±217 mL, P=0.14) or older (-62±82 mL, P=0.72) adults. Likewise, the contribution of PG and EDHF also did not change in both young (-306±222 mL, P=0.68) and older (-108±116 mL, P=0.77) adults. These findings indicate that PG and EDHF do not have an additive effect to NO on the hyperemic response to PLM in both young and older adults. Therefore, the remaining hyperemic response following combined NO, PG, and EDHF inhibition is likely driven by non-endothelial dependent mechanisms. Moreover, these data indicate that 8 weeks of KE specific exercise training significantly improves the hyperemic response to PLM in young but not older adults. Interestingly, the observed improvements to PLM were not directly mediated through the NO, PG, or EDHF pathways but by some other, currently unidentified, mechanism. National Institutes of Health R01HL142603 (to J.D. Trinity) 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.

  PublisherDOI

• Heart Rate and VO₂Kinetics in Patients with Parkinson’s Disease and Orthostatic Hypotension

  Physiology · 2025-05-01 · 1 citations

  articleSenior author

  During exercise, a lower heart rate (HR) has been identified in people with Parkinson’s disease (PD), which is referred to as “chronotropic incompetence” and is often attributed to disease-related impairments in autonomic function. This autonomic dysfunction is likely to slow HR and oxygen uptake (VO 2 ) during exercise initiation, which would result in utilization of anaerobic metabolism, muscle metabolite accumulation, and compromise resistance to neuromuscular fatigue which all negatively impact exercise tolerance. However, little is known about how HR and VO 2 are affected by more severe PD-related impairments in autonomic function, as observed in PD with orthostatic hypotension (PD+OH). Therefore, we quantified and compared the HR and VO 2 response to locomotor exercise in PD+OH and healthy, age-matched adults (CON) and hypothesized that the kinetics of both are slower in PD+OH. HR and VO 2 data were continuously collected during 6-minute bouts of semi-recumbent leg cycling exercise at 1) moderate (80% of gas exchange threshold) and 2) heavy (30% above gas exchange threshold) intensity work rates. Two trials at each intensity were ensemble averaged and fit with monoexponential curves, from which mean response time was calculated. HR kinetics analysis revealed a slower mean response time to the heavy intensity work rate in PD+OH compared to CON (106 ±41 s vs 75 ±40 s, p=0.032), while moderate intensity did not elicit differences between groups (59 ±20 s vs 49 ±29 s, p=0.155). Analysis of VO 2 data identified a slower mean response time for PD+OH compared to CON in both moderate (74 ±11 s vs 67 ±10 s, p=0.045) and heavy (76 ±22 s vs 61 ±10 s, p=0.021) intensity exercise. The results suggest that, in addition to previously identified chronotropic incompetence, PD+OH also exhibit a slower HR and VO 2 time-course response to exercise, particularly in the heavy intensity domain. Due to the metabolic demand of exercise requiring a prompt increase in oxygen delivery, slower kinetic responses may contribute to higher reliance on anaerobic metabolism and influence exercise tolerance or fatigue. This impairment may be a limiting factor the participation of PD+OH in exercise-based therapies or during repeated cardiovascular stresses during activities of daily living. 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.

  PublisherDOI

• Transcriptomic analyses of peripheral blood mononuclear cells reveal age-specific basal and acute exercise responsiveness differences in humans

  American Journal of Physiology-Endocrinology and Metabolism · 2025-07-23 · 3 citations

  articleOpen access

  This study demonstrates that aging alters the transcriptional landscape of PBMCs at rest and in response to acute high-intensity exercise. Older adults exhibited greater transcriptomic responsiveness to exercise, particularly in pathways related to immune signaling and cellular stress. Notably, exercise elicited shared activation of NK cell-mediated processes across age groups, suggesting a conserved immunomodulatory effect. These findings provide molecular insight into how aging and exercise interact to shape immune cell function.

  PublisherDOI

• The influence of biological sex on the metabolic basis of skeletal muscle fatigue <i>in vivo</i>

  The Journal of Physiology · 2025-09-17 · 6 citations

  article

  Abstract This study in humans was designed to evaluate: (1) the overall relationships between muscle fatigue and inorganic phosphate (Pi) and hydrogen ions (H + ) in women and men, and (2) whether the decline in contractile function for a given change in these intramuscular metabolites differs between sexes (i.e. muscle fatigue sensitivity). Sixteen healthy, young individuals (eight women) performed two consecutive (interspersed by 5 min of rest) intermittent isometric single‐leg knee‐extensor trials (60 maximal voluntary contractions; 3 s contraction, 2 s relaxation). Throughout both trials, intramuscular quadriceps [Pi] and [H + ] were quantified using phosphorus magnetic resonance spectroscopy, and quadriceps twitch force ( Q tw ) was measured using electrical femoral nerve stimulation. The exercise‐induced reduction in Q tw was greater in men than in women in both trials (both P &lt; 0.048). In both sexes, the Q tw –[Pi] relationship was unchanged across trials, while the Q tw –[H + ] relationship shifted downwards. The decline in Q tw for a given increase in [Pi] or [H + ] was not different between men and women. The exercise‐induced reduction in Q tw was strongly associated only with Pi accumulation ( r = 0.761, P &lt; 0.001). These results show that, in both sexes, Q tw is more consistently related to Pi than to H + , and that the decrease in Q tw for a given increase in [Pi] and [H + ] does not differ between women and men. This supports that the in vivo metabolic basis of muscle fatigue is similar across sexes, and that differences in the exercise‐induced reduction in contractile function relate to the extent of metabolic disturbance, rather than to an inherent fatigue resistance. image Key points The decline in muscle contractile function during high‐intensity exercise (i.e. muscle fatigue) is generally less in women than in men. Sex‐related differences in the intrinsic resistance to intramuscular metabolites may explain this divergence. We evaluated (1) the overall relationships between muscle fatigue and inorganic phosphate (Pi) and hydrogen ions (H + ) in women and men, and (2) whether the decline in contractile function for a given change in intramuscular metabolites differs between sexes. In both sexes, intramuscular Pi was more consistently related to muscle fatigue compared with H + . For each metabolite (Pi or H + ), the decrease in contractile function for a given intramuscular accumulation was similar in women and men. In conclusion, in vivo the metabolic basis of muscle fatigue is similar between sexes. Sex differences in the magnitude of fatigue are therefore probably not due to an intrinsic resistance to intramuscular metabolites.

  PublisherDOI

• Differential Effects of PB125 and MitoQ Supplementation and Limb Immobilization on Mitochondrial Respiration and Protein Expression in Skeletal Muscle

  Physiology · 2025-05-01

  article

  Mitochondrial dynamics and respiratory capacity contribute to the regulation of cellular redox state and metabolism. Disuse upregulates reactive oxygen species (ROS), disrupting physiological pathways and impairing mitochondria. This study investigated the effects of PB125 (a nuclear factor erythroid-2-like 2 [Nrf2] activator) and MitoQ (a mitochondria-targeted antioxidant) with two weeks of supplementation and two weeks of limb immobilization on mitochondrial respiration and protein expression. We hypothesized that both supplements would decrease ROS and improve mitochondrial respiration. Twenty-four participants (15F/9M, 27±7 years old) were randomly assigned to Placebo (n=8, 6F/2M), PB125 (n=9, 4F/5M), or MitoQ (n=7, 5F/2M). Skeletal muscle biopsies were taken from the vastus lateralis at baseline (V1), after 2 weeks of supplementation (V2), and after 2 weeks of limb immobilization with supplementation (V3). Mitochondrial respiration and ADP sensitivity (apparent K m ) were measured in permeabilized muscle fibers via high-resolution respirometry. Protein levels of mitochondrial complexes and mitochondrial dynamics were assessed by western blot. Skeletal muscle superoxide levels were assessed by electron paramagnetic resonance spectroscopy using mitoTEMPO-H. After 2 weeks of supplementation (V1-V2), State 3 complex I respiration (7.0±2.4 pmol/s/mg to 12.4±3.7 pmol/s/mg, p=0.030) and maximal respiration (59.1±12.5 pmol/s/mg to 73.8±14.5 pmol/s/mg, p=0.050) were enhanced with MitoQ, with no effect in PB125 or placebo (both, p&gt;0.05). There was a differential effect of supplementation on K m , where those receiving placebo had an increase in K m from V1 to V3 (237±85 to 406±194 µM ADP, p=0.032), MitoQ had a decrease from V2 to V3 (612±259 to 345±88 µM ADP, p=0.032), and there was no effect on PB125 (p&gt;0.05). From V1-V2, both PB125 and MitoQ improved only one mitochondrial protein. PB125 supplementation increased Drp1 (10.7%, p=0.031), while MitoQ supplementation increased complex I (30.0%, p=0.036). Following disuse (V2-V3), both PB125 and MitoQ saw a decrease in multiple mitochondrial proteins. PB125 had a decrease in Mfn2 (-20.0%, p=0.012), complex III (-50.7%, p=0.035), and complex V (-34.0%, p=0.046), while with MitoQ, there was a decline in PGC1α (-24.5%, p=0.035), Parkin (-10.2%, p=0.009), and complex IV (-10.7%, p=0.037). No significant changes in mitochondrial superoxide were observed for any supplementation (all, p&gt;0.05). MitoQ supplementation enhanced mitochondrial respiration, likely through complex I upregulation, however, neither PB125 nor MitoQ fully protected against reductions in mitochondrial proteins following disuse. R01HL142603VA Merit I01CX001999 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.

  PublisherDOI

• α‐Adrenergic regulation of skeletal muscle blood flow during exercise in patients with heart failure with preserved ejection fraction

  The Journal of Physiology · 2024-06-06 · 9 citations

  articleOpen access

  Abstract Heart failure with preserved ejection fraction (HFpEF) has been characterized by lower blood flow to exercising limbs and lower peak oxygen utilization (), possibly associated with disease‐related changes in sympathetic (α‐adrenergic) signaling. Thus, in seven patients with HFpEF (70 ± 6 years, 3 female/4 male) and seven controls (CON) (66 ± 3 years, 3 female/4 male), we examined changes (%Δ) in leg blood flow (LBF, Doppler ultrasound) and leg to intra‐arterial infusion of phentolamine (PHEN, α‐adrenergic antagonist) or phenylephrine (PE, α 1 ‐adrenergic agonist) at rest and during single‐leg knee‐extension exercise (0, 5 and 10 W). At rest, the PHEN‐induced increase in LBF was not different between groups, but PE‐induced reductions in LBF were lower in HFpEF (−16% ± 4% vs . −26% ± 5%, HFpEF vs . CON; P &lt; 0.05). During exercise, the PHEN‐induced increase in LBF was greater in HFpEF at 10 W (16% ± 8% vs . 8% ± 5%; P &lt; 0.05). PHEN increased leg in HFpEF (10% ± 3%, 11% ± 6%, 15% ± 7% at 0, 5 and 10 W; P &lt; 0.05) but not in controls (−1% ± 9%, −4% ± 2%, −1% ± 5%; P = 0.24). The ‘magnitude of sympatholysis’ (PE‐induced %Δ LBF at rest – PE‐induced %Δ LBF during exercise) was lower in patients with HFpEF (−6% ± 4%, −6% ± 6%, −7% ± 5% vs . −13% ± 6%, −17% ± 5%, −20% ± 5% at 0, 5 and 10 W; P &lt; 0.05) and was positively related to LBF, leg oxygen delivery, leg , and the PHEN‐induced increase in LBF ( P &lt; 0.05). Together, these data indicate that excessive α‐adrenergic vasoconstriction restrains blood flow and limits of the exercising leg in patients with HFpEF, and is related to impaired functional sympatholysis in this patient group. image Key points Sympathetic (α‐adrenergic)‐mediated vasoconstriction is exaggerated during exercise in patients with heart failure with preserved ejection fraction (HFpEF), which may contribute to limitations of blood flow, oxygen delivery and oxygen utilization in the exercising muscle. The ability to adequately attenuate α 1 ‐adrenergic vasoconstriction (i.e. functional sympatholysis) within the vasculature of the exercising muscle is impaired in patients with HFpEF. These observations extend our current understanding of HFpEF pathophysiology by implicating excessive α‐adrenergic restraint and impaired functional sympatholysis as important contributors to disease‐related impairments in exercising muscle blood flow and oxygen utilization in these patients.

  PublisherOA PDFDOI

• The effcacy of short-term tetrahydrobiopterin administration to improve locomotor muscle microvascular function in heart failure with preserved ejection fraction

  Physiology · 2024-05-01

  article

  Background: Patients with heart failure with preserved ejection fraction (HFpEF) exhibit locomotor muscle microvascular dysfunction due partly to reduced nitric oxide (NO) bioavailability. Tetrahydrobiopterin (BH 4 ) is a requisite cofactor for the enzymatic production of NO by NO synthase (NOS). BH 4 insuffciency promotes NOS uncoupling, which reduces NO production and augments cellular oxidative stress. Given the potential of BH 4 to improve NO bioavailability, we tested the hypothesis that short-term BH 4 administration would improve locomotor muscle microvascular function in patients with HFpEF. Methods: Eight patients with HFpEF (74±7 years; 31.3±4.9 kg/m 2 ) participated in a randomized, double-blind, crossover study, having consumed either BH 4 (Sapropterin, 10 mg/kg) or placebo for 10 days, separated by a 14-day washout period. Locomotor muscle microvascular function was assessed as leg blood flow (LBF) and leg vascular conductance (LVC) responses to passive leg movement (PLM) before (pre) and after (post) each treatment. PLM-induced LBF and LVC responses were expressed as peak change (Δpeak) or total hyperemic response (area under the curve above baseline; AUC). Results: LBF Δpeak did not change following BH 4 (267 ± 136 mL/min vs. 250 ± 101 mL/min) or placebo (317 ± 119 mL/min vs. 269 ± 97 mL/min) administration (pre vs. post; p&gt;0.05). Similarly, LVC Δpeak was unchanged following either BH 4 (396 ± 165 mL/min/100mmHg vs. 465 ± 180 mL/min/100mmHg) or placebo (579 ± 238 mL/min/100mmHg vs. 496 ± 185 mL/min/100mmHg) administration (pre vs. post; p&gt;0.05). The changes in LBF AUC and LVC AUC were not affected by either treatment (LBF AUC ; BH 4 : Δ91 ± 103 mL vs. Δ82 ± 69 mL; placebo: Δ148 ± 119 mL vs. Δ87 ± 81 mL; LVC AUC ; BH 4: Δ65 ± 55 mL/100mmHg vs. Δ98 ± 78 mL/100mnHg; placebo: Δ182 ± 127 mL/100mmHg vs. Δ105 ± 94 mL/100mmHg) (pre vs. post; p&gt;0.05). Conclusion: Short-term BH 4 administration did not improve locomotor muscle microvascular function in patients with HFpEF. This project was funded, in part, by the National Institutes of Health (HL118313, D.W.W.; T32HL139451, K.B.; the U.S. Department of Veterans Affairs (I01RX001311, D.W.W.; IK2RX003670, to K.B.), and the American Heart Association (18POST33960192; K.B.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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Frequent coauthors

• Russell S. Richardson

  University of Utah

  227 shared

• Joel D. Trinity

  University of Utah

  113 shared

• D. Walter Wray

  University of Utah

  74 shared

• Jesse C. Craig

  University of Utah

  72 shared

• Catherine L. Jarrett

  Geriatric Research Education and Clinical Center

  66 shared

• Jayson R. Gifford

  62 shared

• Stephen M. Ratchford

  University of Utah

  59 shared

• Thomas J. Barstow

  Kansas State University

  53 shared

Labs

• Utah Vascular Research Laboratory (UVRL)PI

Education

• Ph.D.

  University of Utah