The human
Dietary Approaches to Stop Hypertension-
Sodium Trial has shown that β-aminoisobutyric
acid (BAIBA) may prevent the development of
salt-sensitive
hypertension (SSHT). However, the specific
antihypertensive mechanism remains unclear in the renal tissues of
salt-sensitive (SS) rats. In this study, BAIBA (100 mg/kg/day) significantly attenuated SSHT via increased
nitric oxide (NO) content in the renal medulla, and it induced a significant increase in NO synthesis substrates (
L-arginine and
malic acid) in the renal medulla. BAIBA enhanced the activity levels of total
NO synthase (NOS), inducible NOS, and constitutive NOS. BAIBA resulted in increased
fumarase activity and decreased
fumaric acid content in the renal medulla. The high-
salt diet (HSD) decreased
fumarase expression in the renal cortex, and BAIBA increased
fumarase expression in the renal medulla and renal cortex. Furthermore, in the renal medulla, BAIBA increased the levels of
ATP,
ADP,
AMP, and
ADP/
ATP ratio, thus further activating AMPK phosphorylation. BAIBA prevented the decrease in renal medullary antioxidative defenses induced by the HSD. In conclusion, BAIBA's
antihypertensive effect was underlined by the phosphorylation of AMPK, the prevention of
fumarase's activity reduction caused by the HSD, and the enhancement of NO content, which in concert attenuated SSHT in SS rats.