scholarly journals Pro-inflammatory Vascular Stress in Spontaneously Hypertensive Rats Associated With High Physical Activity Cannot Be Attenuated by Aldosterone Blockade

2021 ◽  
Vol 8 ◽  
Author(s):  
Rolf Schreckenberg ◽  
Annemarie Wolf ◽  
Christian Troidl ◽  
Sakine Simsekyilmaz ◽  
Klaus-Dieter Schlüter
Keyword(s):  
Physical Activity ◽  
Vascular Wall ◽  
Hypertensive Rats ◽  
Running Wheel ◽  
Spontaneously Hypertensive ◽  
High Physical Activity ◽  
Beneficial Effects ◽  
Voluntary Running ◽  
Running Wheel Exercise ◽  
Wheel Activity

The effect of high physical activity, performed as voluntary running wheel exercise, on inflammation and vascular adaptation may differ between normotensive and spontaneously hypertensive rats (SHRs). We investigated the effects of running wheel activity on leukocyte mobilization, neutrophil migration into the vascular wall (aorta), and transcriptional adaptation of the vascular wall and compared and combined the effects of high physical activity with that of pharmacological treatment (aldosterone antagonist spironolactone). At the start of the 6th week of life, before hypertension became established in SHRs, rats were provided with a running wheel over a period of 10-months'. To investigate to what extent training-induced changes may underlie a possible regression, controls were also generated by removal of the running wheel for the last 4 months. Aldosterone blockade was achieved upon oral administration of Spironolactone in the corresponding treatment groups for the last 4 months. The number of circulating blood cells was quantified by FACS analysis of peripheral blood. mRNA expression of selected proteins was quantified by RT-PCR. Histology and confocal laser microscopy were used to monitor cell migration. Although voluntary running wheel exercise reduced the number of circulating neutrophils in normotensive rats, it rather increased it in SHRs. Furthermore, running wheel activity in SHRs but not normotensive rats increased the number of natural killer (NK)-cells. Except of the increased expression of plasminogen activator inhibitor (PAI)-1 and reduction of von Willebrand factor (vWF), running wheel activity exerted a different transcriptional response in the vascular tissue of normotensive and hypertensive rats, i.e., lack of reduction of the pro-inflammatory IL-6 in vessels from hypertensive rats. Spironolactone reduced the number of neutrophils; however, in co-presence with high physical activity this effect was blunted. In conclusion, although high physical activity has beneficial effects in normotensive rats, this does not predict similar beneficial effects in the concomitant presence of hypertension and care has to be taken on interactions between pharmacological approaches and high physical activity in hypertensives.

scholarly journals Untypical Metabolic Adaptations in Spontaneously Hypertensive Rats to Free Running Wheel Activity Includes Uncoupling Protein-3 (UCP-3) and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Annemarie Wolf ◽  
Hanna Sarah Kutsche ◽  
Felix Atmanspacher ◽  
Meryem Sevval Karadedeli ◽  
Rolf Schreckenberg ◽  
...  
Keyword(s):  
Physical Activity ◽  
Hypertensive Rats ◽  
Running Wheel ◽  
Spontaneously Hypertensive ◽  
Glut 1 ◽  
Hepatic Expression ◽  
Glut 4 ◽  
Metabolic Adaptations ◽  
Free Running ◽  
Wheel Activity

Obesity and hypertension are common risk factors for cardiovascular disease whereas an active lifestyle is considered as protective. However, the interaction between high physical activity and hypertension is less clear. Therefore, this study investigates the impact of high physical activity on the muscular and hepatic expression of glucose transporters (Glut), uncoupling proteins (UCPs), and proprotein convertase subtilisin/kexin type 9 (PCSK9) in spontaneously hypertensive rats (SHRs). Twenty-four female rats (12 normotensive rats and 12 SHRs) were divided into a sedentary control and an exercising group that had free access to running wheels at night for 10 months. Blood samples were taken and blood pressure was determined. The amount of visceral fat was semi-quantitatively analyzed and Musculus gastrocnemius, Musculus soleus, and the liver were excised. Acute effects of free running wheel activity were analyzed in 15 female SHRs that were sacrificed after 2 days of free running wheel activity. M. gastrocnemius and M. soleus differed in their mRNA expression of UCP-2, UCP-3, GLUT-4, and PCSK9. Hypertension was associated with lower levels of UCP-2 and PCSK9 mRNA in the M. gastrocnemius, but increased expression of GLUT-1 and GLUT-4 in the M. soleus. Exercise down-regulated UCP-3 in the M. soleus in both strains, in the M. gastrocnemius only in normotensives. In SHRs exercise downregulated the expression of UCP-2 in the M. soleus. Exercise increased the expression of GLUT-1 in the M. gastrocnemius in both strains, and that of GLUT-4 protein in the M. soleus, whereas it increased the muscle-specific expression of PCSK9 only in normotensive rats. Effects of exercise on the hepatic expression of cholesterol transporters were seen only in SHRs. As an acute response to exercise increased expressions of the myokine IL-6 and that of GLUT-1 were found in the muscles. This study, based on transcriptional adaptations in striated muscles and livers, shows that rats perform long-term metabolic adaptations when kept with increased physical activity. These adaptations are at least in part required to stabilize normal protein expression as protein turnover seems to be modified by exercise. However, normotensive and hypertensive rats differed in their responsiveness. Based on these results, a direct translation from normotensive to hypertensive rats is not possible. As genetic differences between normotensive humans and patients with essential hypertension are likely to be present as well, we would expect similar differences in humans that may impact recommendations for non-pharmacological interventions.

P6372Does modification of activity regimes optimize the effect of high physical activity on hypertensive heart disease?

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K.-D Schluter ◽  
R Schreckenberg ◽  
A Wolf ◽  
H Kutsche ◽  
C Troidl ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Life Style ◽  
Work Load ◽  
Running Wheel ◽  
High Physical Activity ◽  
Beneficial Effects ◽  
Active Life ◽  
Free Running ◽  
Wheel Activity

Abstract Aims and background Spontaneously hypertensive rats (SHR) are a suitable model of essential hypertension and allow analyze the progression of hypertension and hypertension-dependent end-organ damage. In this model, acute improvement of physical activity (free running wheel activity) exerts known beneficial effects (such as lowering oxidative stress). However, these initial beneficial effects are lost during the continuation of high physical activity and translate into mal-adaptive processes, suggesting that not any high physical activity exerts beneficial effects. It has been hypothesized that the skeletal muscle release myokines, that contribute to the beneficial effects of exercise. However, myokines, such as IL-6, are induced by an acute increase in work load not by continuous work load. Therefore, we analyzed whether modification of high physical activity, i.e. intermittent free running wheel activity, modify the long-term impact on long lasting hypertension. Methods 38 female SHR aged 6 weeks (pre-hypertensive state) were randomly allocated to one of the following groups: Sedentary (S; standard holding condition) imitating the condition of sedentary life style, high activity (HA; life-long free running wheel) imitating the condition of active life style, temporary activity (TA; 6 months free running wheel and 3 months sedentary) imitating the loss of active life style during ageing, and finally intermittent activity (IA; 10 months repetitive access to running wheels every 4 weeks) imitating altered workloads. All rats were sacrificed at the age of 10 months. Results IA was the only treatment regime that effectively lowered blood pressure (P syst: 186±11 vs. 165±6 mmHg), improved ejection fraction (EF: 56±5 vs. 63±2%), and displayed clear molecular profile of adaptive myocardial hypertrophy rather than mal-adaptive hypertrophy. Moreover, only IA reduced the number of circulating monocytes (377±102 vs. 220±16 /μl), a cell population that immigrated in the left ventricle. The number of monocytes was directly correlated with the expression of MMP12, BNP, ANP, biglycan, collagen-1, actinin, β-MHC, and somatstatin but inversely related to β-adrenoceptor, Glut-4, and UCP3 expression. Finally, IA increased the skeletal expression of IL-6 and decreased the renal expression of AT1 receptors. Conclusion The data confirm the previous findings that not all type of physical activity beneficially affects hypertensive-dependent disease. In contrast, the data support the hypothesis that alterations in work load are required triggering the release of myokines from the skeletal muscle and identify the amount of circulating monocytes as a main trigger of mal-adaptive hypertrophy in these rats. The data are important with respect to optimize life style suggestions for patients with essential hypertension. Acknowledgement/Funding DFG (ERAGON and SFB 1213)

scholarly journals Effects of voluntary exercise on the expression of browning markers in visceral and subcutaneous fat tissue of normotensive and spontaneously hypertensive rats

2021 ◽  
Author(s):  
Meryem Sevval Karadedeli ◽  
Rolf Schreckenberg ◽  
Hanna S. Kutsche ◽  
Klaus-Dieter Schlüter
Keyword(s):  
Physical Activity ◽  
Adipose Tissue ◽  
Spontaneously Hypertensive Rats ◽  
Voluntary Exercise ◽  
Female Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
High Physical Activity ◽  
Fat Depots ◽  
Brown Adipose

AbstractHigh physical activity is important to optimize the function of adipose tissue. Dysfunctional adipose tissue contributes to the development of metabolic stress, chronic inflammation, and hypertension. To improve our current understanding of the interaction between physical exercise and adipose tissue, we analyzed the effect of 10 months voluntary running wheel activity of rats on uncoupling protein (UCP) 1 negative white adipose tissue (visceral and subcutaneous adipose tissue, VWAT and SWAT). Analysis was performed via RT-PCR and immunoblot from adipose tissues depicted from adult normotensive and spontaneously hypertensive female rats. UCP1 negative VWAT differed from UCP1 positive WAT and brown adipose tissue (BAT) from interscapular fat depots, by lacking the expression of UCP1 and low expression of Cidea, a transcriptional co-activator of UCP1. High physical activity affected the expression of five genes in SWAT (Visfatin (up), RBP5, adiponectin, Cidea, and Nrg4 (all down)) but only one gene (Visfatin, up) in VWAT. Furthermore, the expression of these genes is differentially regulated in VWAT and SWAT of normotensive and spontaneously hypertensive rats (SHR) under sedentary conditions (UCP2) and exercise (Visfatin, Cidea, Nrg4). Keeping the animals after 6 months of voluntary exercise under observation for an additional period of 4 months without running wheels, Visfatin, Cidea, and Nrg4 were stronger expressed in VWAT of SHRs than in sedentary control rats. In summary, our study shows that SWAT is more responsible to exercise than VWAT.

scholarly journals Dehulled Adlay Consumption Modulates Blood Pressure in Spontaneously Hypertensive Rats and Overweight and Obese Young Adults

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2305
Author(s):  
Wan-Ju Yeh ◽  
Jung Ko ◽  
Wei-Yi Cheng ◽  
Hsin-Yi Yang
Keyword(s):  
Blood Pressure ◽  
Daily Intake ◽  
Experimental Period ◽  
Overweight And Obesity ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Grain Foods

High blood pressure is a crucial risk factor for many cardiovascular diseases, and a diet rich in whole-grain foods may modulate blood pressure. This study investigated the effects of dehulled adlay consumption on blood pressure in vivo. We initially fed spontaneous hypertensive rats diets without (SHR group) or with 12 or 24% dehulled adlay (SHR + LA and SHR + HA groups), and discovered that it could limit blood pressure increases over a 12-week experimental period. Although we found no significant changes in plasma, heart, and kidney angiotensin-converting enzyme activities, both adlay-consuming groups had lower endothelin-1 and creatinine concentrations than the SHR group; the SHR + HA group also had lower aspartate aminotransferase and uric acid levels than the SHR group did. We later recruited 23 participants with overweight and obesity, and they consumed 60 g of dehulled adlay daily for a six-week experimental period. At the end of the study, we observed a significant decrease in the group’s systolic blood pressure (SBP), and the change in SBP was even more evident in participants with high baseline SBP. In conclusion, our results suggested that daily intake of dehulled adlay had beneficial effects in blood-pressure management. Future studies may further clarify the possible underlying mechanisms for the consuming of dehulled adlay as a beneficial dietary approach for people at risk of hypertension.

scholarly journals Identification of Aortic Proteins Involved in Arterial Stiffness in Spontaneously Hypertensive Rats Treated With Perindopril:A Proteomic Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Danyelle S. Miotto ◽  
Aline Dionizio ◽  
André M. Jacomini ◽  
Anderson S. Zago ◽  
Marília Afonso Rabelo Buzalaf ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Molecular Mechanisms ◽  
Rho Kinase ◽  
Vascular Wall ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Cytoskeleton Organization ◽  
Proteomic Approach

Arterial stiffness, frequently associated with hypertension, is associated with disorganization of the vascular wall and has been recognized as an independent predictor of all-cause mortality. The identification of the molecular mechanisms involved in aortic stiffness would be an emerging target for hypertension therapeutic intervention. This study evaluated the effects of perindopril on pulse wave velocity (PWV) and on the differentially expressed proteins in aorta of spontaneously hypertensive rats (SHR), using a proteomic approach. SHR and Wistar rats were treated with perindopril (SHRP) or water (SHRc and Wistar rats) for 8 weeks. At the end, SHRC presented higher systolic blood pressure (SBP, +70%) and PWV (+31%) compared with Wistar rats. SHRP had higher values of nitrite concentration and lower PWV compared with SHRC. From 21 upregulated proteins in the aortic wall from SHRC, most of them were involved with the actin cytoskeleton organization, like Tropomyosin and Cofilin-1. After perindopril treatment, there was an upregulation of the GDP dissociation inhibitors (GDIs), which normally inhibits the RhoA/Rho-kinase/cofilin-1 pathway and may contribute to decreased arterial stiffening. In conclusion, the results of the present study revealed that treatment with perindopril reduced SBP and PWV in SHR. In addition, the proteomic analysis in aorta suggested, for the first time, that the RhoA/Rho-kinase/Cofilin-1 pathway may be inhibited by perindopril-induced upregulation of GDIs or increases in NO bioavailability in SHR. Therefore, we may propose that activation of GDIs or inhibition of RhoA/Rho-kinase pathway could be a possible strategy to treat arterial stiffness.

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