Background. Cardiac remodeling in uremia is characterized by left ventricular hypertrophy, interstitial fibrosis and microvascular disease. Cardiovascular disease is the leading cause of death in uremic patients, but coronary events alone are not the prevalent cause, sudden death and heart failure are. We studied the cardiac remodeling in experimental uremia, evaluating the isolated effect of parathyroid hormone (PTH) and phosphorus. Methods. Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx); they also received vehicle (V) and PTH at normal (nPTH) or high (hPTH) doses. They were fed with a poor-phosphorus (pP) or rich-phosphorus (rP) diet and were divided into the following groups: ‘Sham’: G1 (V + normal-phosphorus diet (np)) and ‘Nx + PTx’: G2 (nPTH + pP), G3 (nPTH + rP), G4 (hPTH + pP) and G5 (hPTH + rP). After 8 weeks, biochemical analysis, myocardium morphometry and arteriolar morphological analysis were performed. In addition, using immunohistochemical analysis, we evaluated angiotensin II, α-actin, transforming growth factor-beta (TGF-β) and nitrotyrosine, as well as fibroblast growth factor-23 (FGF-23), fibroblast growth factor receptor-1 (FGFR-1) and runt-related transcription factor-2 (Runx-2) expression. Results. Nx animals presented higher serum creatinine levels as well as arterial hypertension. Higher PTH levels were associated with myocardial hypertrophy and fibrosis as well as a higher coronary lesion score. High PTH animals also presented a higher myocardial expression of TGF-β, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of α-actin. Phosphorus overload was associated with higher serum FGF-23 levels and Runx-2, as well as myocardial hypertrophy. FGFR-1 was positive in the cardiomyocytes of all groups as well as in calcified coronaries of G4 and G5 whereas Runx-2 was positive in G3, G4 and G5. Conclusion. In uremia, PTH and phosphorus overload are both independently associated with major changes related to the cardiac remodeling process, emphasizing the need for a better control of these factors in chronic kidney disease.

Objective To evaluate the effect of low-intensity chronic exercise training (ExT) on blood pressure (BP), as well as the cardiac alterations associated with hypertension in aging hypertensive rats. Methods Male spontaneously hypertensive rats (SHR; 21 months old) and their normotensive control Wistar–Kyoto (WKY) rats were submitted to low-intensity training protocol for 13 weeks. BP, cardiac morphological and morphometric analysis, as well as gene expression of fibrotic and inflammatory factors were analyzed at the end of the training period. Results ExT reduced BP and heart rate in aged SHR. Left ventricle hypertrophy, collagen volume fraction and wall-to-lumen ratio of myocardium arterioles were also decreased in trained SHR. However, ExT was unable to reverse the either reduced capillary density or the cardiac myocyte hypertrophy observed in SHR as compared with WKY rats. Trained SHR showed higher metalloproteinase-2/tissue inhibitor metalloproteinase-2 (MMP-2/TIMP-2) ratio and lower levels of α-smooth muscle actin, but similar levels of connective tissue growth factor, transforming growth factor beta or IL-1 beta to that of nontrained SHR. Conclusion Low to moderate-intensity chronic ExT reverses the cardiac alterations associated with hypertension: myocardial arteriole, left ventricle hypertrophy, collagen content and tachycardia. These changes could be consequence or cause of the reduction in BP observed in trained SHR. In addition, ExT does not worsen the underlying inflammatory burden associated with hypertension. Therefore, the data support a beneficial effect of ExT in aging SHR similar to that reported in young or middle-aged individuals, confirming that exercise is a healthy habit that induces cardiac improvements independently of age.