Heme oxygenase-1 alleviates vascular complications associated with metabolic syndrome: Effect on endothelial dependent relaxation and NO production

• It is the first to report on protective effect of HO-1 on vascular toxicity in MetS.
• HO-1 induction virtually abolished the MetS-induced hypertension.
• This suggests HO-1 induction as a protective strategy for MetS vascular toxicity.

Protective effect of Heme oxygenase-1 (HO-1) induction from hypertension was previously reported in a diabetic animal model. Here, the effect of HO-1 induction on vascular complications associated with metabolic syndrome (MetS) was investigated.MetS was induced in rats by fructose drinking for 12 weeks while HO-1 was induced by hemin or curcumin administration in the last 6 weeks. Then, aortic HO-1 protein expression was assessed, blood pressure (BP) was recorded and serum levels of glucose and insulin were measured. Concentration response curves for phenylephrine (PE), KCl, and acetylcholine (ACh) were obtained in thoracic aortic cross sections. Aortic reactive oxygen species (ROS) and nitric oxide (NO) generation were also studied.Both hemin and curcumin significantly inhibited the elevated systolic and diastolic BP seen in MetS animals. While not affected by MetS, HO-1 expression was significantly increased by hemin and curcumin treatment. HO-1 induction did not affect the exaggerated vasoconstriction response to KCl and PE. However, HO-1 induction prevented the impaired relaxation and NO generation in aorta isolated from MetS animals. In addition, the HO inhibitor, tin protoporphyrin, abolished the hemin protective effect on relaxation and NO generation. HO-1 induction prevented the elevated hyperinsulinemia associated with MetS. Furthermore, HO-1 induction inhibited ROS production in aorta isolated from MetS animals.In conclusion, Heme oxygenase-1 alleviates vascular complications associated in MetS through maintaining endothelial-dependent relaxation and NO generation in addition to improving insulin sensitivity.