We aimed to test the hypothesis that an enhanced level of reactive oxygen species (ROS) is primarily responsible for the impairment of nitric oxide (NO)-mediated regulation of arteriolar wall shear stress (WSS) in hyperhomocysteinemia (HHcy). Thus flow\/WSS-induced dilations of pressurized gracilis muscle arterioles (basal diameter: approximately 170 microm) isolated from control (serum Hcy: 6 +\/- 1 microM), methionine diet-induced HHcy rats (4 wk, serum Hcy: 30 +\/- 6 microM), and HHcy rats treated with vitamin C, a known antioxidant (4 wk, 150 mg. kg body wt-1.day-1; serum Hcy: 32 +\/- 10 microM), were investigated. In vessels of HHcy rats, increases in intraluminal flow\/WSS-induced dilations were converted to constrictions. Constrictions were unaffected by inhibition of NO synthesis by N omega-nitro-L-arginine methyl ester (L-NAME). Vitamin C treatment of HHcy rats reversed the WSS-induced arteriolar constrictions to L-NAME-sensitive dilations but did not affect control responses. Similar changes in responses were obtained for the calcium ionophore A-23187. In addition, diastolic and mean arterial blood pressure and serum 8-isoprostane levels (a marker of in vivo oxidative stress) were significantly elevated in rats with HHcy, changes that were normalized by vitamin C treatment. Taken together, our data show that in chronic HHcy long-term vitamin C treatment, by decreasing oxidative stress in vivo, enhanced NO bioavailability, restored the regulation of shear stress in arterioles, and normalized systemic blood pressure. Thus our study provides evidence that oxidative stress is an important in vivo mechanism that is primarily responsible for the development of endothelial dysregulation of WSS in HHcy.<\/p>\n
Zsolt Bagi, Csongor Cseko, Erika T\u00f3th, Akos Koller<\/p>\n
<\/p>\n
Summary We aimed to test the hypothesis that an enhanced level of reactive oxygen species (ROS) is primarily responsible for the impairment of nitric oxide (NO)-mediated regulation of arteriolar wall shear stress (WSS) in hyperhomocysteinemia (HHcy). Thus flow\/WSS-induced dilations of pressurized gracilis muscle arterioles (basal diameter: approximately 170 microm) isolated from control (serum Hcy: 6…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[69],"tags":[545],"_links":{"self":[{"href":"https:\/\/www.healthlibrary.info\/wp-json\/wp\/v2\/posts\/7231"}],"collection":[{"href":"https:\/\/www.healthlibrary.info\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.healthlibrary.info\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.healthlibrary.info\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.healthlibrary.info\/wp-json\/wp\/v2\/comments?post=7231"}],"version-history":[{"count":0,"href":"https:\/\/www.healthlibrary.info\/wp-json\/wp\/v2\/posts\/7231\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.healthlibrary.info\/wp-json\/wp\/v2\/media?parent=7231"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.healthlibrary.info\/wp-json\/wp\/v2\/categories?post=7231"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.healthlibrary.info\/wp-json\/wp\/v2\/tags?post=7231"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}