Voluntary wheel running improves cardiac function in a rodent model of chronic kidney disease (884.15)

The purpose of this investigation was to determine the effect of 4 wk of voluntary wheel running on cardiac performance in the 5/6 ablation-infarction (AI) rat model of chronic kidney disease (CKD). We hypothesized that voluntary wheel running would be effective in preserving cardiac function in AI. Male Sprague-Dawley rats were divided into three study groups: 1) sham, sedentary nondiseased control; 2) AI-SED, sedentary AI; and 3) AI-WR, wheel-running AI. Animals were maintained over a total period of 8 wk following AI and sham surgery. The 8-wk period included 4 wk of disease development followed by a 4-wk voluntary wheel-running intervention/sedentary control period. Cardiac performance was assessed using an isolated working heart preparation. Left ventricular (LV) tissue was used for biochemical tissue analysis. In addition, soleus muscle citrate synthase activity was measured. AI-WR rats performed a low volume of exercise, running an average of 13 ± 2 km, which resulted in citrate synthase activity not different from that in sham animals. Isolated AI-SED hearts demonstrated impaired cardiac performance at baseline and in response to preload/afterload manipulations. Conversely, cardiac function was preserved in AI-WR vs. sham hearts. LV nitrite + nitrate and expression of LV nitric oxide (NO) synthase isoforms 2 and 3 in AI-WR were not different from those of sham rats. In addition, LV H2O2 in AI-WR was similar to that of sham and associated with increased expression of LV superoxide-dismutase-2 and glutathione peroxidase-1/2. The findings of the current study suggest that a low-volume exercise intervention is sufficient to maintain cardiac performance in rats with CKD, potentially through a mechanism related to improved redox homeostasis and increased NO.

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Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00014.2014 ◽

2014 ◽

Vol 307 (4) ◽

pp. F418-F426 ◽

Cited By ~ 11

Author(s):

Christopher R. Martens ◽

James M. Kuczmarski ◽

Jahyun Kim ◽

John J. Guers ◽

M. Brennan Harris ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Vascular Function ◽

Wheel Running ◽

Area Under The Curve ◽

Maximal Response ◽

Sprague Dawley ◽

Voluntary Wheel Running ◽

Sprague Dawley Rats ◽

Voluntary Wheel

Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor l-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endothelium-dependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent ⅚ ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUN+ARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10−9-10−5 M) as indicated by a reduced area under the curve (AUC; 44.56 ± 9.01 vs 100 ± 4.58, P < 0.05) and reduced maximal response (Emax; 59.9 ± 9.67 vs. 94.31 ± 1.27%, P < 0.05). AUC was not improved by ARG treatment but was significantly improved above SED animals in both RUN and RUN+ARG-treated animals. Maximal relaxation was elevated above SED in RUN+ARG animals only. l-[3H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUN+ARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with l-arginine.

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Skeletal muscle metabolic responses to physical activity are muscle type specific in a rat model of chronic kidney disease

Scientific Reports ◽

10.1038/s41598-021-89120-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Keith G. Avin ◽

Meghan C. Hughes ◽

Neal X. Chen ◽

Shruthi Srinivasan ◽

Kalisha D. O’Neill ◽

...

Keyword(s):

Physical Activity ◽

Skeletal Muscle ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Rat Model ◽

Mitochondrial Respiration ◽

Wheel Running ◽

Muscle Metabolism ◽

Voluntary Wheel Running ◽

Voluntary Wheel

AbstractChronic kidney disease (CKD) leads to musculoskeletal impairments that are impacted by muscle metabolism. We tested the hypothesis that 10-weeks of voluntary wheel running can improve skeletal muscle mitochondria activity and function in a rat model of CKD. Groups included (n = 12–14/group): (1) normal littermates (NL); (2) CKD, and; (3) CKD-10 weeks of voluntary wheel running (CKD-W). At 35-weeks old the following assays were performed in the soleus and extensor digitorum longus (EDL): targeted metabolomics, mitochondrial respiration, and protein expression. Amino acid-related compounds were reduced in CKD muscle and not restored by physical activity. Mitochondrial respiration in the CKD soleus was increased compared to NL, but not impacted by physical activity. The EDL respiration was not different between NL and CKD, but increased in CKD-wheel rats compared to CKD and NL groups. Our results demonstrate that the soleus may be more susceptible to CKD-induced changes of mitochondrial complex content and respiration, while in the EDL, these alterations were in response the physiological load induced by mild physical activity. Future studies should focus on therapies to improve mitochondrial function in both types of muscle to determine if such treatments can improve the ability to adapt to physical activity in CKD.

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The Effect of L‐arginine Supplementation & Voluntary Wheel Running on Vascular Function in Rats with Chronic Kidney Disease

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.1136.13 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Christopher R Martens ◽

James M Kuczmarski ◽

Shannon Lennon‐Edwards ◽

David G Edwards

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Vascular Function ◽

Wheel Running ◽

Voluntary Wheel Running ◽

Arginine Supplementation ◽

Voluntary Wheel

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Voluntary wheel running: a useful rodent model for investigating mechanisms of stress robustness and exercise motivation

Current Opinion in Behavioral Sciences ◽

10.1016/j.cobeha.2019.02.001 ◽

2019 ◽

Vol 28 ◽

pp. 78-84 ◽

Cited By ~ 4

Author(s):

Benjamin N Greenwood ◽

Monika Fleshner

Keyword(s):

Wheel Running ◽

Rodent Model ◽

Exercise Motivation ◽

Voluntary Wheel Running ◽

Voluntary Wheel

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Effects of Voluntary Wheel Running on Cardiac Function in Female Rats Receiving Chemical Ovariectomy

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000273104.40566.2d ◽

2007 ◽

Vol 39 (Supplement) ◽

pp. S53

Author(s):

David S. Hydock ◽

Chia-Ying Lien ◽

Carole M. Schneider ◽

Reid Hayward

Keyword(s):

Cardiac Function ◽

Wheel Running ◽

Female Rats ◽

Voluntary Wheel Running ◽

Voluntary Wheel

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Voluntary Wheel Running Has Beneficial Effects in a Rat Model of CKD-Mineral Bone Disorder (CKD-MBD)

Journal of the American Society of Nephrology ◽

10.1681/asn.2019040349 ◽

2019 ◽

Vol 30 (10) ◽

pp. 1898-1909 ◽

Cited By ~ 1

Author(s):

Keith G. Avin ◽

Matthew R. Allen ◽

Neal X. Chen ◽

Shruthi Srinivasan ◽

Kalisha D. O’Neill ◽

...

Keyword(s):

Kidney Disease ◽

Rat Model ◽

Wheel Running ◽

Serum Biochemistry ◽

Left Ventricular ◽

Cystic Kidney Disease ◽

Cystic Kidney ◽

Voluntary Wheel Running ◽

Exercise Interventions ◽

Voluntary Wheel

BackgroundReduced bone and muscle health in individuals with CKD contributes to their higher rates of morbidity and mortality.MethodsWe tested the hypothesis that voluntary wheel running would improve musculoskeletal health in a CKD rat model. Rats with spontaneous progressive cystic kidney disease (Cy/+ IU) and normal littermates (NL) were given access to a voluntary running wheel or standard cage conditions for 10 weeks starting at 25 weeks of age when the rats with kidney disease had reached stage 2–3 of CKD. We then measured the effects of wheel running on serum biochemistry, tissue weight, voluntary grip strength, maximal aerobic capacity (VO2max), body composition and bone micro-CT and mechanics.ResultsWheel running improved serum biochemistry with decreased creatinine, phosphorous, and parathyroid hormone in the rats with CKD. It improved muscle strength, increased time-to-fatigue (for VO2max), reduced cortical porosity and improved bone microarchitecture. The CKD rats with voluntary wheel access also had reduced kidney cystic weight and reduced left ventricular mass index.ConclusionsVoluntary wheel running resulted in multiple beneficial systemic effects in rats with CKD and improved their physical function. Studies examining exercise interventions in patients with CKD are warranted.

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Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00801.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. H3254-H3264 ◽

Cited By ~ 27

Author(s):

David S. Hydock ◽

Chia-Ying Lien ◽

Carole M. Schneider ◽

Reid Hayward

Keyword(s):

Physical Activity ◽

Cardiac Function ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Cardiac Dysfunction ◽

Wheel Running ◽

Female Rats ◽

Voluntary Wheel Running ◽

Developed Pressure ◽

Voluntary Wheel

Reducing testosterone and estrogen levels with a luteinizing hormone-releasing hormone agonist such as Zoladex (i.e., chemical gonadectomy) is a common treatment for many prostate and breast cancer patients, respectively. There are reports of surgical gonadectomy inducing cardiac dysfunction, and exercise has been shown to be cardioprotective under these circumstances. Minimal research has been done investigating the effects of chemical gonadectomy and increased physical activity on cardiac function. The purpose of this investigation was to examine the effects of chemical gonadectomy and physical activity on cardiac function. Male (M) and female (F) Sprague-Dawley rats received either Zoladex treatment (Zol) that suppressed gonadal function for 8 wk or control implants (Con) and either were allowed unlimited access to voluntary running wheels (WR) or remained sedentary (Sed) throughout the treatment period. In vivo and ex vivo left ventricle (LV) function were then assessed, and myosin heavy chain (MHC) expression was analyzed to help explain LV functional differences. Hearts from M Sed+Zol exhibited significantly lower aortic blood flow velocity, developed pressure, and maximal rate of pressure development and higher β-MHC expression than M Sed+Con. Hearts from F Sed+Zol exhibited significantly lower LV wall thicknesses, fractional shortening, and developed pressure and higher β-MHC expression than F Sed+Con. This cardiac dysfunction was not evident in hearts from M or F WR+Zol, and this was associated with a preservation of the MHC isoform distribution. Thus an 8-wk chemical gonadectomy with Zoladex promoted cardiac dysfunction in male and female rats, and voluntary wheel running protected against this cardiac dysfunction.

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The Copenhagen chronic kidney disease echo study (COInCYDE)

European Heart Journal ◽

10.1093/ehjci/ehaa946.3326 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

N Landler ◽

S Bro ◽

B Feldt-Rasmussen ◽

D Hansen ◽

A.L Kamper ◽

...

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Cohort Study ◽

Kidney Disease ◽

Cardiac Function ◽

Left Ventricular ◽

Funding Source ◽

Ckd Stage ◽

Significant Difference ◽

Stage 1

Abstract Background The cardiovascular mortality of patients with chronic kidney disease (CKD) is 2–10 times higher than in the average population. Purpose To estimate the prevalence of abnormal cardiac function or structure across the stages CKD 1 to 5nonD. Method Prospective cohort study. Patients with CKD stage 1 to 5 not on dialysis, aged 30 to 75 (n=875) and age-/sex-matched controls (n=173) were enrolled consecutively. All participants underwent a health questionnaire, ECG, morphometric and blood pressure measurements. Blood and urine were analyzed. Echocardiography was performed. Left ventricle (LV) hypertrophy, dilatation, diastolic and systolic dysfunction were defined according to current ESC guidelines. Results 63% of participants were men. Mean age was 58 years (SD 12.6 years). Mean eGFR was 46.7 mL/min/1,73 m (SD 25.8) for patients and 82.3 mL/min/1,73 m (SD 13.4) for controls. The prevalence of elevated blood pressure at physical exam was 89% in patients vs. 53% in controls. Patients were more often smokers and obese. Left ventricular mass index (LVMI) was slightly, albeit insignificantly elevated at CKD stages 1 & 2 vs. in kontrols: 3.1 g/m2, CI: −0.4 to 6.75, p-value 0.08. There was no significant difference in LV-dilatation between patients and controls. Decreasing diastolic and systolic function was observed at CKD stage 3a and later: LVEF decreased 0.95% (CI: −1.5 to −0.2), GLS increased 0.5 (CI: 0.3 to 0.8), and OR for diastolic dysfunction increased 3.2 (CI 1.4 to 7.3) pr. increment CKD stage group. Conclusion In accordance to previous studies, we observe in the CPHCKD cohort study signs of early increase of LVMI in patients with CKD stage 1 & 2. Significant decline in systolic and diastolic cardiac function is apparent already at stage 3 CKD. Figure 1. Estimated GFR vs. GLS & histogram of GLS Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): The Capital Region of Denmark

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