title: Methylmercury affects cerebrovascular reactivity to angiotensin II and acetylcholine via Rho-kinase and nitric oxide pathways in mice.
abstract: OBJECTIVE
  Methylmercury (MeHg) exposure results in increased risk of hypertension and cardiovascular diseases. In this study, we aimed to investigate whether the in vivo exposure of MeHg in mice affects blood pressure and basilar arterial responses to angiotensin II (Ang II) and acetylcholine (ACh), which are important modulators of cerebrovascular autoregulation.
  
  
  METHODS
  Mice were exposed to MeHg (40ppm) in drinking water for 21days. Blood pressure was measured in conscious mice by an indirect tail-cuff method. Functional studies of the isolated arteries' response to vasoactive substances were performed using a micro-organ-bath system.
  
  
  RESULTS
  Systolic and mean blood pressures were significantly increased after 2 and 3weeks of treatment with MeHg, respectively. Ang II-induced contraction in an isolated basilar artery, which is mediated via Rho-kinase activation, was increased in MeHg-treated mice. ACh-induced relaxation, which is dependent on NO production from the endothelial cells, was decreased in MeHg-treated mice. However, alterations of vascular responses to Ang II and ACh were not observed in the isolated thoracic aorta.
  
  
  CONCLUSIONS
  This study demonstrated that the cerebral vasculature appears to be particularly sensitive to in vivo exposure of MeHg. Our results suggest that in vivo MeHg increases blood pressure and causes alterations in the cerebrovascular reactivity in response to Ang II and ACh through enhancement of Rho-kinase activity and inhibition of NO bioavailability, respectively.
authors.affiliation: Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Kagoshima University, Japan.
authors.forename: Md Zahorul
authors.initials: MZ
authors.lastname: Islam
authors.affiliation: Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Kagoshima University, Japan.
authors.forename: Cuong
authors.initials: C
authors.lastname: Van Dao
authors.affiliation: Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Kagoshima University, Japan. Electronic address: shira-m@vet.kagoshima-u.ac.jp.
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Shiraishi
authors.affiliation: Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Kagoshima University, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage* / Q000378:metabolism; D000804:Angiotensin II / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D062186:Arterial Pressure / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D008767:Methylmercury Compounds; D000804:Angiotensin II; D009569:Nitric Oxide; D054460:rho-Associated Kinases; D000109:Acetylcholine
keywords: Acetylcholine; Angiotensin II; Cerebral artery; Methylmercury; Rho-kinase