Swimming Exercise Ameliorates Hypertension-Induced Kidney Dysfunction via Alleviating Renal Interstitial Fibrosis and Apoptosis

Abstract

<b><i>Background:</i></b> Hypertensive nephropathy is one of the major causes of ESRD. Exercise has been considered a nonpathological therapy for hypertension and its complications, yet mechanisms remain unclear. We sought to investigate whether periodic swimming could ameliorate hypertension-induced kidney dysfunction and its underlying mechanisms. <b><i>Methods:</i></b> Four-week male spontaneously hypertensive rats (SHRs) were randomly divided into the hypertension group (SHR, <i>n</i> = 8) and exercise group (SE, <i>n</i> = 8, 60 min swimming/day, 6 days per week, for 8 weeks). Wistar-Kyoto rats (WKY, <i>n</i> = 8) were served as a sedentary normotensive group. Bodyweight and blood pressure (BP) were recorded weekly. After 8-week sedentary or swimming exercise, lipids profile, BUN, and Cr were measured. The renal interstitial fibrosis was examined by the histopathological analysis using Masson’s trichrome staining and hematoxylin and eosin staining. The kidney cell apoptosis was tested by TUNEL staining. The expressions of critical proteins responsible for the TGF-β1/Smad signaling of fibrosis, that is, TGF-β1, Smad2/3, and Smad7, as well as apoptosis related proteins, Bax and Bcl-2 in kidney cortex tissues were measured. <b><i>Results:</i></b> The 8-week swimming exercise reduced BP and bodyweight, lowered concentrations of BUN, and serum Cr, compared with SHR. Exercise remarkably inhibited hypertension-induced tubular degeneration, cellular cluster, and tubular cell swelling as well as glomerular degeneration in the kidney cortical tissues, attenuated renal interstitial fibrosis, and renal cell apoptosis. Moreover, expressions of TGF-β1, Smad2/3, and Bax were higher in the SHR than the WKY, which were significantly suppressed by the exercise. In contrast, hypertension-reduced expressions of Smad7 and Bcl-2 were enhanced by the swimming exercise. Strong correlations were found between kidney function indices, blood lipids, and key protein expressions. <b><i>Conclusion:</i></b> Our results demonstrate beneficial effects of the periodic swimming on ameliorating hypertension-induced kidney dysfunction highlighting the potential of swimming exercise as a nonpathological therapy for early prevention of hypertension-caused kidney diseases.