Exaggerated Exercise Pressor Reflex in Type 2 Diabetes: Potential Role of Oxidative Stress

Overview

Journal Auton Neurosci

Publisher Elsevier

Specialty Neurology

Date 2019 Nov 1

PMID 31669797

Citations 13

Authors

Ann-Katrin Grotle

Audrey J Stone

Affiliations

Soon will be listed here.

Abstract

Type 2 diabetes mellitus (T2DM) leads to exaggerated cardiovascular responses to exercise, in part due to an exaggerated exercise pressor reflex. Accumulating data suggest excessive oxidative stress contributes to an exaggerated exercise pressor reflex in cardiovascular-related diseases. Excessive oxidative stress is also a primary underlying mechanism for the development and progression of T2DM. However, whether oxidative stress plays a role in mediating the exaggerated exercise pressor reflex in T2DM is not known. Therefore, this review explores the potential role of oxidative stress leading to increased activation of the afferent arm of the exercise pressor reflex. Several lines of evidence support direct and indirect effects of oxidative stress on the exercise pressor reflex. For example, intramuscular ROS may directly and indirectly (by attenuating contracting muscle blood flow) increase group III and IV afferent activity. Oxidative stress is a primary underlying mechanism for the development of neuropathic pain, which in turn is associated with increased group III and IV afferent activity. These are the same type of afferents that evoke muscle pain and the exercise pressor reflex. Furthermore, oxidative stress-induced release of inflammatory mediators may modulate afferent activity. Collectively, these alterations may result in a positive feedback loop that further amplifies the exercise pressor reflex. An exaggerated reflex increases the risk of adverse cardiovascular events. Thus, identifying the contribution of oxidative stress could provide a potential therapeutic target to reduce this risk in T2DM.

Citing Articles

Brazilian Guideline for Exercise Test in the Adult Population - 2024.

Carvalho T, Freitas O, Chalela W, Hossri C, Milani M, Buglia S Arq Bras Cardiol. 2024; 121(3):e20240110.

PMID: 38896581 PMC: 11656589. DOI: 10.36660/abc.20240110.

Lower vascular conductance responses to handgrip exercise are improved following acute antioxidant supplementation in young individuals with post-traumatic stress disorder.

Weggen J, Darling A, Autler A, Hogwood A, Decker K, Richardson J Exp Physiol. 2024; 109(6):992-1003.

PMID: 38711207 PMC: 11140166. DOI: 10.1113/EP091762.

Exercise training modalities in prediabetes: a systematic review and network meta-analysis.

Zhang H, Guo Y, Hua G, Guo C, Gong S, Li M Front Endocrinol (Lausanne). 2024; 15:1308959.

PMID: 38440785 PMC: 10911289. DOI: 10.3389/fendo.2024.1308959.

Neural control of the circulation during exercise in heart failure with reduced and preserved ejection fraction.

Bunsawat K, Skow R, Kaur J, Wray D Am J Physiol Heart Circ Physiol. 2023; 325(5):H998-H1011.

PMID: 37682236 PMC: 10907034. DOI: 10.1152/ajpheart.00214.2023.

Blood flow restriction training activates the muscle metaboreflex during low-intensity sustained exercise.

Mannozzi J, Al-Hassan M, Kaur J, Lessanework B, Alvarez A, Massoud L J Appl Physiol (1985). 2023; 135(2):260-270.

PMID: 37348015 PMC: 10393340. DOI: 10.1152/japplphysiol.00274.2023.

References

Kaufman M, Rotto D, Rybicki K . Pressor reflex response to static muscular contraction: its afferent arm and possible neurotransmitters. Am J Cardiol. 1988; 62(8):58E-62E. DOI: 10.1016/s0002-9149(88)80013-4. View

Sandstrom M, Zhang S, Bruton J, Silva J, Reid M, Westerblad H . Role of reactive oxygen species in contraction-mediated glucose transport in mouse skeletal muscle. J Physiol. 2006; 575(Pt 1):251-62. PMC: 1819411. DOI: 10.1113/jphysiol.2006.110601. View

Hansen J, Sander M, Thomas G . Metabolic modulation of sympathetic vasoconstriction in exercising skeletal muscle. Acta Physiol Scand. 2000; 168(4):489-503. DOI: 10.1046/j.1365-201x.2000.00701.x. View

Janig W . Mechanical allodynia generated by stimulation of unmyelinated afferent nerve fibres. J Physiol. 2011; 589(Pt 18):4407-8. PMC: 3208212. DOI: 10.1113/jphysiol.2011.217083. View

Muller M, Drew R, Blaha C, Mast J, Cui J, Reed A . Oxidative stress contributes to the augmented exercise pressor reflex in peripheral arterial disease patients. J Physiol. 2012; 590(23):6237-46. PMC: 3530129. DOI: 10.1113/jphysiol.2012.241281. View

Fadel P, Farias Iii M, Gallagher K, Wang Z, Thomas G . Oxidative stress and enhanced sympathetic vasoconstriction in contracting muscles of nitrate-tolerant rats and humans. J Physiol. 2011; 590(2):395-407. PMC: 3285073. DOI: 10.1113/jphysiol.2011.218917. View

Scott J, Coombes J, Prins J, Leano R, Marwick T, Sharman J . Patients with type 2 diabetes have exaggerated brachial and central exercise blood pressure: relation to left ventricular relative wall thickness. Am J Hypertens. 2008; 21(6):715-21. DOI: 10.1038/ajh.2008.166. View

OConnor E, Green S, Kiely C, OShea D, Egana M . Differential effects of age and type 2 diabetes on dynamic vs. peak response of pulmonary oxygen uptake during exercise. J Appl Physiol (1985). 2015; 118(8):1031-9. DOI: 10.1152/japplphysiol.01040.2014. View

Gliemann L, Nyberg M, Hellsten Y . Nitric oxide and reactive oxygen species in limb vascular function: what is the effect of physical activity?. Free Radic Res. 2013; 48(1):71-83. DOI: 10.3109/10715762.2013.835045. View

10.

Hanna R, Kaufman M . Role played by purinergic receptors on muscle afferents in evoking the exercise pressor reflex. J Appl Physiol (1985). 2002; 94(4):1437-45. DOI: 10.1152/japplphysiol.01011.2002. View

11.

Womack L, Peters D, Barrett E, Kaul S, Price W, Lindner J . Abnormal skeletal muscle capillary recruitment during exercise in patients with type 2 diabetes mellitus and microvascular complications. J Am Coll Cardiol. 2009; 53(23):2175-83. PMC: 2722783. DOI: 10.1016/j.jacc.2009.02.042. View

12.

Crecelius A, Kirby B, Voyles W, Dinenno F . Nitric oxide, but not vasodilating prostaglandins, contributes to the improvement of exercise hyperemia via ascorbic acid in healthy older adults. Am J Physiol Heart Circ Physiol. 2010; 299(5):H1633-41. PMC: 2993219. DOI: 10.1152/ajpheart.00614.2010. View

13.

Kingwell B, Formosa M, Muhlmann M, Bradley S, McConell G . Type 2 diabetic individuals have impaired leg blood flow responses to exercise: role of endothelium-dependent vasodilation. Diabetes Care. 2003; 26(3):899-904. DOI: 10.2337/diacare.26.3.899. View

14.

Goodpaster B, Bertoldo A, Ng J, Azuma K, Pencek R, Kelley C . Interactions among glucose delivery, transport, and phosphorylation that underlie skeletal muscle insulin resistance in obesity and type 2 Diabetes: studies with dynamic PET imaging. Diabetes. 2013; 63(3):1058-68. PMC: 3931396. DOI: 10.2337/db13-1249. View

15.

Copp S, Kim J, Ruiz-Velasco V, Kaufman M . The mechano-gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in decerebrate rats. J Physiol. 2015; 594(3):641-55. PMC: 4930067. DOI: 10.1113/JP271714. View

16.

Sanderson B, Rollins K, Hopkins T, Butenas A, Felice K, Ade C . GsMTx4 reduces the reflex pressor response during dynamic hindlimb skeletal muscle stretch in decerebrate rats. Physiol Rep. 2019; 7(1):e13974. PMC: 6328922. DOI: 10.14814/phy2.13974. View

17.

Mittleman M, Siscovick D . Physical exertion as a trigger of myocardial infarction and sudden cardiac death. Cardiol Clin. 1996; 14(2):263-70. DOI: 10.1016/s0733-8651(05)70279-4. View

18.

Eriksson J, Lindstrom J, Tuomilehto J . Potential for the prevention of type 2 diabetes. Br Med Bull. 2002; 60:183-99. DOI: 10.1093/bmb/60.1.183. View

19.

Thaning P, Bune L, Hellsten Y, Pilegaard H, Saltin B, Rosenmeier J . Attenuated purinergic receptor function in patients with type 2 diabetes. Diabetes. 2009; 59(1):182-9. PMC: 2797920. DOI: 10.2337/db09-1068. View

20.

Dib-Hajj S, Cummins T, Black J, Waxman S . Sodium channels in normal and pathological pain. Annu Rev Neurosci. 2010; 33:325-47. DOI: 10.1146/annurev-neuro-060909-153234. View