Astragaloside IV improves the isoproterenol-induced vascular dysfunction via attenuating eNOS uncoupling-mediated oxidative stress and inhibiting ROS-NF-κB pathways

• Astragaloside IV (AsIV) improved the vascular dysfunction of the aorta induced by Iso.
• AsIV inhibited eNOS uncoupling-mediated oxidative stress in aorta induced by Iso.
• AsIV regulated the aortic protein expressions of NF-κB p65 and its inhibitor IκB-α.
• AsIV downregulated aortic genes expression of proinflammatory cytokines.

ObjectiveOxidative stress and inflammation are regarded as two important triggers of endothelial dysfunction and play pivotal role in progression of vascular damage associated with cardiac hypertrophy. Our previous studies demonstrated that astragaloside IV (AsIV) could protect against cardiac hypertrophy in rats induced by isoproterenol (Iso), but its effects on the aorta are not known. In present study, we aimed to assess the effects of AsIV on Isoinduced vascular dysfunction.MethodsSprague-Dawley (SD) rats were treated with Iso (10 mg/kg/d) alone or in combination with AsIV (50 mg/kg/d).ResultsCompared with Isotreated alone, AsIV significantly reduced the ratios of heart weight/body weight and left ventricular weight/body weight. AsIV ameliorated the increased vasoconstriction response to phenylephrine induced by Iso and suppressed superoxide anion generation in rat aorta, increased endothelial nitric oxide synthase (eNOS) dimer/monomer ratio and its critical cofactor tetrahydrobiopterin (BH4) content in aorta as well as the NO production in the serum, reduced the plasmatic peroxynitrite (ONOO–). Moreover, in contrast with Isotreatment alone, AsIV decreased the ratio of nuclear-to-cytosolic protein expression of the NF-κB p65 subunit while enhanced its inhibited protein expression of IκB-α, down-regulated mRNA expression of IL-1β, IL-6 and TNF-α of the aorta.ConclusionsThe present study suggested that AsIV protects against Isoinduced vascular dysfunction probably via attenuating eNOS uncoupling-mediated oxidative stress and inhibiting ROS-NF-κB pathways.