The Effect of Alpha-Lipoic Acid on Mitochondrial Superoxide and Glucocorticoid-Induced Hypertension

الملخص EN

Aims.

To examine the effect of alpha-lipoic acid, an antioxidant with mitochondrial superoxide inhibitory properties, on adrenocorticotrophic hormone- (ACTH-HT) and dexamethasone-induced hypertensions (DEX-HT) in rats and if any antihypertensive effect is mediated via mitochondrial superoxide inhibition.

Methods.

In a prevention study, rats received ground food or alpha-lipoic-acid-laced food (10 mg/rat/day) for 15 nights.

Saline, adrenocorticotrophic hormone (ACTH, 0.2 mg/kg/day), or dexamethasone (DEX, 10 μg/rat/day) was injected subcutaneously from day 5 to day 11.

In a reversal study, rats received alpha-lipoic-acid-laced food 4 days after commencement of saline or DEX.

Tail-cuff systolic blood pressure (SBP) was measured second daily.

Kidney mitochondrial superoxide was examined using (MitoSOX) Red (MitoSOX) via flow cytometry.

Results.

SBP was increased by ACTH (P<0.0005) and DEX (P<0.0005).

Alpha-lipoic acid alone did not alter SBP.

With alpha-lipoic acid pretreatment, SBP was increased by ACTH (P′<0.005) but not by DEX.

Alpha-lipoic partially prevented ACTH-HT (P′<0.0005) and fully prevented DEX-HT (P′<0.0005) but failed to reverse DEX-HT.

ACTH and DEX did not increase MitoSOX signal.

In ACTH-hypertensive rats, high-dose alpha-lipoic acid (100 mg/rat/day) did not decrease SBP further but raised MitoSOX signal (P<0.001), suggesting prooxidant activity.

Conclusion.

Glucocorticoid-induced hypertension in rats is prevented by alpha-lipoic acid via mechanisms other than mitochondrial superoxide reduction.