Methylmercury affects cerebrovascular reactivity to angiotensin II and acetylcholine via Rho-kinase and nitric oxide pathways in mice

Life Sci. 2016 Feb 15:147:30-8. doi: 10.1016/j.lfs.2016.01.033. Epub 2016 Jan 22.

Abstract

Aims: 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.

Main 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.

Key findings: 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.

Significance: 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.

Keywords: Acetylcholine; Angiotensin II; Cerebral artery; Methylmercury; Rho-kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / administration & dosage*
  • Acetylcholine / metabolism
  • Angiotensin II / administration & dosage*
  • Angiotensin II / metabolism
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Arterial Pressure / drug effects
  • Blood Pressure / drug effects
  • Hypertension
  • Male
  • Methylmercury Compounds / toxicity*
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide / metabolism*
  • Vasoconstriction / drug effects
  • Vasodilation / drug effects
  • rho-Associated Kinases / metabolism*

Substances

  • Methylmercury Compounds
  • Angiotensin II
  • Nitric Oxide
  • rho-Associated Kinases
  • Acetylcholine