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Adverse cardiac remodelling in spontaneously hypertensive rats: acceleration by high aerobic exercise intensity
Author(s) -
da Costa Rebelo Rui Manuel,
Schreckenberg Rolf,
Schlüter KlausDieter
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.241141
Subject(s) - aerobic exercise , hypertensive heart disease , medicine , endocrinology , captopril , cardiology , blood pressure , angiotensin converting enzyme , serca , renin–angiotensin system , muscle hypertrophy , intensity (physics) , sed , heart failure , atpase , chemistry , enzyme , biochemistry , physics , quantum mechanics
Key points• Physical exercise is recommended as first line therapy for hypertensive patients. However, studies investigating long‐term effects of high intensity exercise on the progression of hypertensive heart disease have revealed conflicting results. • We show that high intensity aerobic exercise accelerates hypertensive heart disease and improves fibrosis. • Surprisingly, high intensity aerobic exercise in the presence of an angiotensin converting enzyme inhibitor not only attenuated training induced mal‐adaptation but exerts positive repair processes. These effects were independent of blood pressure effects. • The results of this study provide evidence that high physical activity in hypertensives must be considered as an important risk factor rather than a therapeutic intervention.Abstract In the present study it was hypothesized that voluntary aerobic exercise favours a pro‐fibrotic phenotype and promotes adverse remodelling in hearts from spontaneously hypertensive rats (SHRs) in an angiotensin II‐dependent manner. To test this, female SHRs at the age of 1 year were started to perform free running wheel exercise. Captopril was used to inhibit the renin–angiotensin system (RAS). Normotensive rats and SHRs kept in regular cages were used as sedentary controls. Training intensity, expressed as mean running velocity, was positively correlated with the left ventricular mRNA expression of TGF‐β 1 , collagen‐III and biglycan but negatively correlated with the ratio of sarcoplasmic reticulum Ca 2+ ‐ATPase (SERCA)2a to Na + –Ca 2+ exchanger (NCX). A pro‐fibrotic phenotype was verified by Picrosirius red staining. Sixty‐seven per cent of SHRs performing free running wheel exercise died either spontaneously or had to be killed during a 6 month follow‐up. In the presence of captopril, aerobic exercise did not show a similar positive correlation between training intensity and the expression of fibrotic markers. Moreover, in SHRs receiving captopril and performing free running wheel exercise, a training intensity‐dependent reverse remodelling of the SERCA2a‐to‐NCX ratio was observed. None of these rats died spontaneously or had to be killed. In captopril‐treated SHRs performing exercise, expression of mRNA for decorin, a natural inhibitor of TGF‐β 1 , was up‐regulated. Despite these differences between SHR‐training groups with and without captopril, positive training effects (lower resting heart rate and no progression of hypertension) were found in both groups. In conclusion, high aerobic exercise induces an angiotensin II‐dependent adverse remodelling in chronic pressure overloaded hearts. However, high physical activity can potentially induce reverse remodelling in the presence of RAS inhibition.