title: Superoxide modulates myogenic contractions of mouse afferent arterioles.
abstract: Reactive oxygen species enhance or impair autoregulation. Because superoxide is a vasoconstrictor, we tested the hypothesis that stretch generates superoxide that mediates myogenic responses. Increasing perfusion pressure of mouse isolated perfused renal afferent arterioles from 40 to 80 mm Hg reduced their diameter by 13.3±1.8% (P<0.001) and increased reactive oxygen species (ethidium: dihydroethidium fluorescence) by 9.8±2.3% (P<0.05). Stretch-induced fluorescence was reduced significantly (P<0.05) by incubation with Tempol (3.7±0.8%), pegylated superoxide dismutase (3.2±1.0%), or apocynin (3.5±0.9%) but not by pegylated catalase, L-nitroarginine methylester, or Ca(2+)-free medium, relating it to Ca(2+)-independent vascular superoxide. Compared with vehicle, basal tone and myogenic contractions were reduced significantly (P<0.05) by pegylated superoxide dismutase (5.4±0.8), Tempol (4.1±1.0%), apocynin (1.0±1.3%), and diphenyleneiodinium (3.9±0.9%) but not by pegylated catalase (10.1±1.6%). L-Nitroarginine methylester enhanced basal tone, but neither it (15.8±3.3%) nor endothelial NO synthase knockout (10.2±1.8%) significantly changed myogenic contractions. Tempol had no further effect after superoxide dismutase but remained effective after catalase. H(2)O(2) >50 μmol/L caused contractions but at 25 μmol/L inhibited myogenic responses (7.4±0.8%; P<0.01). In conclusion, increasing the pressure within afferent arterioles led to Ca(2+)-independent increased vascular superoxide production from nicotinamide adenine dinucleotide phosphate oxidase, which enhanced myogenic contractions largely independent of NO, whereas H(2)O(2) impaired pressure-induced contractions but was not implicated in the normal myogenic response.
authors.affiliation: Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007, USA.
authors.forename: En Yin
authors.initials: EY
authors.lastname: Lai
authors.forename: Anton
authors.initials: A
authors.lastname: Wellstein
authors.forename: William J
authors.initials: WJ
authors.lastname: Welch
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wilcox
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001160:Arterioles / Q000378:metabolism*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013481:Superoxides; D009569:Nitric Oxide; C056165:acetovanillone; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D013482:Superoxide Dismutase; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester