Abstract
Purpose: According to the current therapeutic guidelines of the WHO physical activity and exercise are recommended as first-line therapy of arterial hypertension. Previous results lead to the conclusion, however, that hearts of spontaneously hypertensive rats (SHR) with established hypertension cannot compensate for the haemodynamic stresses caused by long-term exercise. The current study was initiated to investigate the effects of aerobic exercise on the cardiac remodeling as the sole therapeutic measure before and during hypertension became established.Methods: Beginning at their 6th week of life, six SHR were provided with a running wheel over a period of 6 months. Normotensive Wistar rats served as non-hypertensive controls.Results: In Wistar rats and SHR, voluntary exercise led to cardioprotective adaptation reactions that were reflected in increased mitochondrial respiration, reduced heart rate and improved systolic function. Exercise also had antioxidant effects and reduced the expression of maladaptive genes (TGF-β1, CTGF, and FGF2). However, at the end of the 6-months' training, the echocardiograms revealed that SHR runners developed a restrictive cardiomyopathy. The induction of lysyl oxidase (LOX), which led to an increased network of matrix proteins and a massive elevation in collagen III expression, was identified as the underlying cause.Conclusions: Running-induced adaptive mechanisms effectively counteract the classic remodeling of hearts subject to chronic pressure loads. However, with sustained running stress, signaling pathways are activated that have a negative effect on left ventricular relaxation. Our data suggest that the induction of LOX may play a causative role in the diagnosed filling disorder in trained SHR.
Highlights
Arterial hypertension is of central importance as a direct risk factor for the development of numerous cardiovascular diseases
With an average speed of 3.2 km/h the Wistar significantly surpassed the speed of the spontaneously hypertensive rats (SHR) (2.5 km/h)
The efficiency of the pyruvate respiration increased in the running Wistar by 25 ± 4% (LV) or 61 ± 10% compared to the non-running controls
Summary
Arterial hypertension is of central importance as a direct risk factor for the development of numerous cardiovascular diseases. There is little information available regarding the effects of physical activity and sport on the cardiovascular system in cases of existing hypertension (Schlüter et al, 2010). The results of a number of studies based on animal experiments suggest that senescent rats with established hypertension do not compensate for additional running-induced hemodynamic stresses and cannot benefit from the associated cellular adaptation mechanisms (Schultz et al, 2007; da Costa Rebelo et al, 2012). The stimulation of the sympathetic nervous system with subsequent activation of the renin-angiotensin system (RAAS) as well as induction of pro-fibrotic mediators such as transforming growth factor-β (TGF-β) and biglycan are largely responsible for these effects (O’Keefe et al, 2012; van de Schoor et al, 2016)
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