Transforming Growth Factor-β-mediated attenuation of cardio-renal oxidative stress, inflammation and fibrosis by L-arginine in fludrocortisone acetate induced-hypertensive rats.

Uncontrolled hypertension is a primary contributor to tissue damage in multiple organs, including the heart and kidneys. In this study, we explored the protective roles of L-arginine in a mineralocorticoid-induced rat model of hypertension. To induce hypertension and subsequent organ damage, rats were nephrectomized unilaterally and fed with the mineralocorticoid fludrocortisone acetate and dietary salt (FCA-Salt). These rats were treated with L-arginine for 28 days, and subsequent tests were performed. Biochemical analysis revealed the increased level of inflammation and oxidative stress biomarkers in the plasma, heart, and kidney of the FCA-salt-treated rats. L-arginine treatment decreased the oxidative stress marker malondialdehyde (MDA) by 18 %, 22 %, and 18 % in the heart, kidney, and plasma, respectively. L-arginine also attenuated the advanced oxidative protein products (AOPP). The activity of superoxide dismutase (SOD) increased by 62 %, 45 %, and 16 % in the heart, kidney, and plasma, respectively, in the L-arginine-treated animals compared to the FCA-Salt group. Significant augmentation was also revealed for the nitric oxide (NO), catalase (CAT), and reduced glutathione (GSH). The plasma levels of the kidney function biomarkers uric acid and creatinine were significantly improved after L-arginine treatment. Furthermore, L-arginine remarkably reduced the elevated plasma cytokines IL-1β, IL-17A, TNF-α, and TGF-β1 in FCA-salt-induced hypertensive rats. Histopathological data showed a reduction in fibrosis and tissue damage by L-arginine in the FCA-salt-treated group. We propose that L-arginine could be an effective agent in preventing cardiac and renal dysfunction in hypertensive rats.