TY - JOUR
T1 - Xanthine oxidase-derived reactive oxygen species convert flow-induced arteriolar dilation to constriction in hyperhomocysteinemia
T2 - Possible role of peroxynitrite
AU - Bagi, Zsolt
AU - Ungvari, Zoltan
AU - Koller, Akos
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - We hypothesized that in hyperhomocysteinemia (HHcy), flow-induced arteriolar constriction is due to an enhanced generation of reactive oxygen and/or nitrogen species, causing an impairment of nitric oxide (NO) and prostaglandin mediation of the response. Changes in diameter of isolated, pressurized (at 80 mm Hg) gracilis muscle arterioles (diameter ≈ 170 μm) from control and methionine diet-induced HHcy rats were measured by videomicroscopy. Increases in intraluminal flow (from 0 to 25 μL/min) resulted in NO- and prostaglandin-mediated dilations of control arterioles (maximum, control, 30±4 μm) but elicited significant constrictions of HHcy arterioles (maximum, HHcy, -32±3 μm), which were abolished by the thromboxane A2 receptor blocker SQ 29,548. Intraluminal administration of superoxide dismutase plus catalase did not affect flow-mediated dilations of control arterioles, but in HHcy arterioles, it reversed the flow-induced constrictions to dilations (maximum 18±4 μm), which were abolished by an NO synthase inhibitor. Flow-induced constrictions of HHcy arterioles were prevented by the presence of the xanthine oxidase inhibitor oxypurinol [but not by the NAD(P)H-oxidase inhibitor diphenyleneiodonium] and by urate, a known peroxynitrite scavenger. Also, authentic peroxynitrite elicited arteriolar constrictions (-31±8 μm) that were eliminated by urate and SQ 29,548. Thus, we suggest that in HHcy, xanthine oxidase-derived superoxide scavenges NO released to flow, forming peroxynitrite, which promotes release of thromboxane A2, resulting in arteriolar constriction.
AB - We hypothesized that in hyperhomocysteinemia (HHcy), flow-induced arteriolar constriction is due to an enhanced generation of reactive oxygen and/or nitrogen species, causing an impairment of nitric oxide (NO) and prostaglandin mediation of the response. Changes in diameter of isolated, pressurized (at 80 mm Hg) gracilis muscle arterioles (diameter ≈ 170 μm) from control and methionine diet-induced HHcy rats were measured by videomicroscopy. Increases in intraluminal flow (from 0 to 25 μL/min) resulted in NO- and prostaglandin-mediated dilations of control arterioles (maximum, control, 30±4 μm) but elicited significant constrictions of HHcy arterioles (maximum, HHcy, -32±3 μm), which were abolished by the thromboxane A2 receptor blocker SQ 29,548. Intraluminal administration of superoxide dismutase plus catalase did not affect flow-mediated dilations of control arterioles, but in HHcy arterioles, it reversed the flow-induced constrictions to dilations (maximum 18±4 μm), which were abolished by an NO synthase inhibitor. Flow-induced constrictions of HHcy arterioles were prevented by the presence of the xanthine oxidase inhibitor oxypurinol [but not by the NAD(P)H-oxidase inhibitor diphenyleneiodonium] and by urate, a known peroxynitrite scavenger. Also, authentic peroxynitrite elicited arteriolar constrictions (-31±8 μm) that were eliminated by urate and SQ 29,548. Thus, we suggest that in HHcy, xanthine oxidase-derived superoxide scavenges NO released to flow, forming peroxynitrite, which promotes release of thromboxane A2, resulting in arteriolar constriction.
KW - Arterioles
KW - Flow-induced constriction
KW - Homocysteine
KW - Reactive oxygen species
KW - Thromboxane A
KW - Xanthine oxidase
UR - http://www.scopus.com/inward/record.url?scp=0036141841&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036141841&partnerID=8YFLogxK
U2 - 10.1161/hq0102.101127
DO - 10.1161/hq0102.101127
M3 - Article
C2 - 11788457
AN - SCOPUS:0036141841
SN - 1079-5642
VL - 22
SP - 28
EP - 33
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 1
ER -