Abstract
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.
Highlights
A high level of physical activity is recommended to reduce the risk of hypertension and related diseases [1]
The number of circulating natural killer cells (NK-cells), B cells, CD4+ and CD8+ T cells, neutrophils, and monocytes was analyzed in blood samples from normotensive rats shortly before the end of the trial
Ten months running wheel exercise had no effect on these counts with neutrophils being an exception
Summary
A high level of physical activity is recommended to reduce the risk of hypertension and related diseases [1]. This assumption is based at least in part on findings showing that hypertension is associated with sterile vascular inflammation and mobilization of pro-inflammatory leukocytes [2, 3]. Hypertension is characterized as primary hypertension that means no organic causes can be found that are responsible for the development of high blood pressure. In ∼60% genetic factors are the triggers and underlying causes of hypertension [5]. According to the current knowledge, the development of high blood pressure levels in SHRs is based on polygenic causes
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