Effects of α-lipoic acid on deoxycorticosterone acetate–salt-induced hypertension in rats

Abstract

We investigated the potential of natural occurring antioxidant α-lipoic acid to prevent hypertension and hypertensive tissue injury induced by deoxycorticosterone acetate (DOCA) and salt in rats. Two weeks after the start of DOCA–salt treatment, the rats were given α-lipoic acid (10 or 100 mg/kg/day, s.c.) or its vehicle for 2 weeks. Uninephrectomized rats without DOCA–salt treatment served as sham-operated controls. In vehicle-treated DOCA–salt rats, systolic blood pressure increased markedly after 3–4 weeks. Daily administration of 100 mg/kg α-lipoic acid for 2 weeks suppressed the increase in systolic blood pressure, whereas 10 mg/kg α-lipoic acid did not affect the progression of DOCA–salt-induced hypertension. When the degree of vascular hypertrophy of the aorta was morphometrically evaluated at 4 weeks, there were significant increases in media cross-sectional area in vehicle-treated DOCA–salt rats compared with sham-operated rats. The development of vascular hypertrophy was markedly suppressed by α-lipoic acid at 100 mg/kg but not at 10 mg/kg. Histopathological examination of the kidney in vehicle-treated DOCA–salt rats revealed fibrinoid-like necrosis in glomeruli and thickening of small arteries. In these animals, creatinine clearance decreased, and fractional excretion of Na +, urinary excretion of protein and N-acetyl-β-glucosaminidase increased. Such renal lesions and dysfunctions were ameliorated in DOCA–salt rats given α-lipoic acid. In addition, a marked increase in endothelin-1 content in both the aorta and kidney was evident in vehicle-treated DOCA–salt rats compared with findings in sham-operated rats. Significant attenuation of this increase occurred in α-lipoic acid-treated DOCA–salt rats. These results suggest that administration of α-lipoic acid to DOCA–salt hypertensive rats lessens the increased blood pressure and protects against renal and vascular injuries, possibly through the suppression of renal and vascular endothelin-1 overproduction.