Effects and Mechanisms of Aerobic Exercise on Myocardial AGEs/RAGE-p38 MAPK-NF- κ B Pathway in SHR Rats

Objective To investigate the effects of aerobic swimming exercise on blood pressure, cardiac function, and the myocardial AGEs/RAGE-p38 MAPK-NF-κB signaling pathway in spontaneously hypertensive rats (SHR).

Twenty-four male Wistar-Kyoto (WKY) rats were randomly assigned to three control subgroups (C-0, C-4, C-8; n=8 each). Fifty-six SHRs were allocated into seven subgroups (S-0, S-4, S-8, SE-4, LE-4, SE-8, and LE-8; n=8each) to receive different swimming intervention protocols. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured via the tail-cuff method. Cardiac parameters, including ejection fraction (EF), fractional shortening (FS), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and stroke volume (SV), were assessed using echocardiography. Myocardial morphological alterations were observed through hematoxylin-eosin (HE) staining, and myocardial hydroxyproline content was quantified using the alkaline hydrolysis method. Furthermore, the myocardial expressions of advanced glycation end products (AGEs), receptor for AGEs (RAGE), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK), and nuclear factor-kappa B (NF-κ) were detected by immunohistochemistry (IHC).

Aerobic exercise significantly reduced blood pressure in SHRs, partially improved cardiac function and myocardial architecture, and decreased hydroxyproline content (except in the SE-4 group). Furthermore, the exercise intervention downregulated the expressions of AGEs, RAGE (except in the SE-4 group), p-p38 MAPK, and NF-κ, with efficacy varying according to exercise duration and intervention cycles.

Aerobic exercise alleviates the progression of hypertension and mitigates the risk of cardiac dysfunction in SHRs by inhibiting myocardial glycation. This cardioprotective effect may be mediated by the suppression of p38 MAPK activation and the subsequent reduction of NF-κ nuclear translocation. Competing Interest Statement The authors have declared no competing interest.