[Aerobic exercise improves renal fibrosis in spontaneously hypertensive rats].

Objective: To study the effects of aerobic exercise training on renal fibrosis in spontaneously hypertensive rats (SHR), and to explore the protective effect of exercise on renal damage in hypertensive rats. Methods: Eight-week-old male SHR and Wistar Kyoto rats of the same age (WKY) were randomly divided into 4 groups (n=6): sedentary WKY control group (WKY-S), sedentary SHR control group (SHR-S), low-intensity exercise group (SHR-L) and medium-intensity exercise group (SHR-M). SHR-L group and SHR-M group were set at a slope of 0° at 14 m/min (35% of the maximum aerobic speed) and 20 m/min (50% of the maximum aerobic speed), running on a sports treadmill for 14 weeks, 5 times a week, and 60 min each time. WKY-S and SHR-S groups were kept quietly. Blood pressure was measured 72 hours after exercise training. And the serum levels of creatinine (Scr) and BUN were detected. The morphology of renal tissue was observed by hematoxylin and eosin (HE) staining. The collagen deposition of renal tissue was observed by Masson staining, and the renal collagen volume fraction (CVF) was calculated. Results: Compared with WKY-S group, blood pressure, serum Scr and BUN, kidney CVF levels and AngⅡ, AT1R, TGF-ß, α-SMA, CTGF expressions in SHR-S group were increased significantly (P＜0.05). Compared with SHR-S group, blood pressure, serum Scr and BUN, kidney CVF level and AngⅡ, AT1R, TGF-ß, α-SMA, CTGF expressions in SHR-L and SHR-M groups were decreased significantly (P＜0.05) and the decreasing trend was more obvious in SHR-M group (P＜0.05). Conclusion: Aerobic exercise can improve renal fibrosis and renal function in spontaneously hypertensive rats by inhibiting the AngⅡ-AT1R-TGF-ß pathway.

Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise.

Moderate-intensity exercise training has been regarded a healthy way to alleviate kidney fibrosis by the transforming growth factor-beta (TGFß) signaling pathway. However, the impact of different intensity exercise training on renal function is unknown, and the underlying mechanism is also unclear. The purpose of this study is to explore the effect of lactic acid in different intensity exercise training on renal fibrosis in spontaneous hypertension. Masson's trichrome staining, immunohistochemistry, lactic acid kit, and Western blotting were applied on the excised renal tissue from six male Wistar-Kyoto rats (WKY) and 18 male spontaneously hypertensive rats (SHR), which were randomly divided into a sedentary hypertensive group (SHR), moderate-intensity exercise hypertensive group (SHR-M), and high-intensity exercise hypertensive group (SHR-H). The results revealed that renal and blood lactic acid, as well as the key fibrotic protein levels of transient receptor potential vanilloid 4 (TRPV4), TGFß-1, phospho-Smad2/3 (p-Smad2/3), and connective tissue growth factor (CTGF), were significantly decreased in the SHR-M group when compared with the SHR and SHR-H groups. In further in vitro experiments, we selected normal rat kidney interstitial fibroblast (NRK-49F) cells. By immunofluorescence and Western blotting techniques, we found that TRPV4 antagonists (RN-1734) markedly inhibited lactate-induced fibrosis. In conclusion, compared with previous studies, high-intensity exercise training (HIET) can cause adverse effects (renal damage and fibrosis). High concentrations of lactic acid can aggravate renal fibrosis conditions via activating TRPV4-TGFß1-SMAD2/3-CTGF-mediated renal fibrotic pathways in spontaneous hypertension. This finding might provide new ideas for treating hypertensive nephropathy with different intensity exercise in the future.

Effects of different intensities of continuous training on vascular inflammation and oxidative stress in spontaneously hypertensive rats.

We aimed to study the effects and underlying mechanism of different intensities of continuous training (CT) on vascular inflammation and oxidative stress in spontaneously hypertensive rats (SHR). Rats were divided into five groups (n = 12): Wistar-Kyoto rats sedentary group (WKY-S), sedentary group (SHR-S), low-intensity CT group (SHR-L), medium-intensity CT group (SHR-M) and high-intensity CT group (SHR-H). Changes in body mass, heart rate and blood pressure were recorded. The rats were euthanized after 14 weeks, and blood and vascular tissue samples were collected. Haematoxylin and Eosin staining was used to observe the aortic morphology, and Western blot was used to detect the expression of mesenteric artery proteins. After CT, the mean arterial pressures improved in SHR-L and SHR-M and increased in SHR-H compared with those in SHR-S. Vascular inflammation and oxidative stress levels significantly subsided in SHR-L and SHR-M (p < 0.05), whereas in SHR-H, only vascular inflammation significantly subsided (p < 0.05), and oxidative stress remained unchanged (p > 0.05). AMPK and SIRT1/3 expressions in SHR-L and SHR-M were significantly up-regulated than those in SHR-S (p < 0.05). These results indicated that low- and medium-intensity CT can effectively reduce the inflammatory response and oxidative stress of SHR vascular tissue, and high-intensity CT can improve vascular tissue inflammation but not oxidative stress.