title: Heme oxygenase-1 alleviates vascular complications associated with metabolic syndrome: Effect on endothelial dependent relaxation and NO production.
abstract: 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 12weeks while HO-1 was induced by hemin or curcumin administration in the last 6weeks. 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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, King Abdulaziz University, Saudi Arabia; Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Egypt. Electronic address: helbassossy@kau.edu.sa.
authors.forename: Hany M
authors.initials: HM
authors.lastname: El-Bassossy
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Egypt.
authors.forename: Nadia
authors.initials: N
authors.lastname: Hassan
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Egypt.
authors.forename: Mohamed N M
authors.initials: MN
authors.lastname: Zakaria
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000503:physiopathology; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D066298:In Vitro Techniques; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D000109:Acetylcholine
keywords: Aorta; Haem oxygenase-1; Hypertension; Metabolic syndrome