Response of Protein Disulfide Isomerase A1 Expression of Cardiac Myocytes to High- and Moderate-Intensity Exercise Training and Alpha-Lipoic Acid in Hypertensive Rats

Hypertension is associated with vascular remodeling, which is supported by the protein disulfide isomerase A1 (PDIA1). Exercise training has beneficial effects on vascular function in subjects with hypertension. Alpha lipoic acid (ALA) is a powerful biological antioxidant. However, the role of exercise training and ALA on PDIA1 are not well understood. The aim of the present study was to investigate effects of training with different intensities and ALA supplementation on PDIA1 expression in cardiomyocytes of hypertensive rats.

In this experimental study, 35 male Wistar rats (age: eight weeks, weight: 190-220 g) were randomly divided into seven groups: control, hypertensive, hypertensive+ALA, hypertensive+high intensity interval training (HIIT), hypertensive+moderate-intensity training (MIT), hypertensive+HIIT+ALA, and hypertensive+MIT+ALA. Hypertension was induced by three weeks of L-NAME administration (40 mg/kg/day). The HIIT and MIT protocols was performed five days a week for six weeks. The HIIT protocol consisted of 10 bouts of four minute-running at 80–85% of Vmax, and the MIT protocol consisted of 13 bouts of four minute-running at 55–60% of Vmax. In the supplementation groups, 20 mg/kg of ALA was administered orally once a day. Immunohistochemistry staining was used to study protein expression.

Induction of hypertension significantly decreased PDIA1 expression compared to the control group (p=0.001). Moreover, PDIA1 expression increased significantly in the hypertensive+ALA (p=0.023), HIIT (p=0.001), MIT (p=0.007), MIT+ hypertensive+ALA (p=0.0001) and HIIT+ hypertensive+ALA (p=0.0001) group compared to the control group.

Hypertension is associated with decreased cardiac PDIA1 level, and both HIIT and MIT along with ALA supplementation are effective in increasing cardiac PDIA1 expression in hypertension.