title: Vascular hyperpermeability in response to inflammatory mustard oil is mediated by Rho kinase in mice systemically exposed to arsenic.
abstract: The mechanisms underlying vascular dysfunction and cardiovascular disease induced by chronic arsenic exposure are not completely understood. We have previously shown that mice chronically fed sodium arsenite are hypersensitive to the permeability-increasing effects of inflammatory mustard oil. The aim of this study was to investigate whether RhoA/Rho kinase (ROCK)-mediated vascular leakage (hyperpermeability) is induced by mustard oil in mice systemically exposed to arsenic. Animals were orally fed water (control group) or sodium arsenite for 8weeks. We compared the blood pressure and microvessel density of the ears between these two groups. Both control and arsenic groups exhibited a similar mean arterial pressure and microvessel density. Microvessel permeability changes that occurred following mustard oil treatment in the presence of Y-27632, a ROCK inhibitor, were quantified using the Evans blue (EB) technique and vascular labeling with carbon particles. Both the excessive leakiness of EB and the high density of carbon-labeled microvessels upon stimulation with mustard oil in the arsenic-fed mice were reduced by Y-27632 treatment. However, RhoA and ROCK2 expression levels were similar between control and arsenic-fed mice. We further investigated ROCK2 levels and ROCK activity in the ears following mustard oil challenge. ROCK2 levels in mouse ears treated with mustard oil were higher in the arsenic group as compared with the control group. Following mustard oil application, ROCK activity was significantly higher in the arsenic-fed mice compared with the control mice. These findings indicate that increased ROCK2 levels and enhanced ROCK activity are responsible for mustard oil-induced vascular hyperpermeability in arsenic-fed mice.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. jaychen@kmu.edu.tw
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Chen
authors.forename: Chun-Chih
authors.initials: CC
authors.lastname: Liu
authors.forename: Shin-Yin
authors.initials: SY
authors.lastname: Huang
authors.forename: Shean-Jaw
authors.initials: SJ
authors.lastname: Chiou
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D001151:Arsenic / Q000494:pharmacology*; D001794:Blood Pressure; D002199:Capillary Permeability; D002244:Carbon / Q000737:chemistry; D005070:Evans Blue / Q000494:pharmacology; D007249:Inflammation; D008297:Male; D051379:Mice; D008833:Microcirculation; D009149:Mustard Plant / Q000378:metabolism; D010938:Plant Oils / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000577:Amides; D010938:Plant Oils; D011725:Pyridines; C108830:Y 27632; D005070:Evans Blue; D002244:Carbon; D054460:rho-Associated Kinases; D001151:Arsenic; C027793:mustard oil