title: Remodeling of Afferent Arterioles From Mice With Oxidative Stress Does Not Account for Increased Contractility but Does Limit Excessive Wall Stress.
abstract: Because superoxide dismutase (SOD) knockout enhances arteriolar remodeling and contractility, we hypothesized that remodeling enhances contractility. In the isolated and perfused renal afferent arterioles from SOD wild type (+/+) and gene-deleted mice, contractility was assessed from reductions in luminal diameter with perfusion pressure from 40 to 80 mm Hg (myogenic responses) or angiotensin II (10(-6) mol/L), remodeling from media:lumen area ratio, superoxide (O2 (·-)) and hydrogen peroxide (H2O2) from fluorescence microscopy, and wall stress from wall tension/wall thickness. Compared with +/+ strains, arterioles from SOD1-/-, SOD2+/-, and SOD3-/- mice developed significantly (P<0.05) more O2 (·-) with perfusion pressure and angiotensin II and significantly increased myogenic responses (SOD1-/-: -20.7±2.2% versus -12.7±1.6%; SOD2+/-: -7.4±1.3% versus -12.6±1.4%; and SOD3-/-: -9.1±1.9% versus -15.8±2.2%) and angiotensin II contractions and ≈2-fold increased media:lumen ratios. Media:lumen ratios correlated with myogenic responses (r(2) =0.23; P<0.01), angiotensin II contractions (r(2)=0.57; P<0.0001), and active wall tension (r(2) =0.19; P<0.01), but not with active wall stress (r(2)=0.08; NS). Differences in myogenic responses among SOD3 mice were abolished by bath addition of SOD and were increased 3 days after inducing SOD3 knockout (-26.9±1.7% versus -20.1±0.7%; P<0.05), despite unchanged media:lumen ratios (2.01±0.09 versus 2.02±0.03; NS). We conclude that cytosolic, mitochondrial, or extracellular O2 (·-) enhance afferent arteriolar contractility and remodeling. Although remodeling does not enhance contractility, it does prevent the potentially damaging effects of increased wall stress.
authors.affiliation: From the Department of Medicine, Division of Nephrology and Hypertension, Hypertension, Kidney and Vascular Research Center, Georgetown University, Washington, DC (L.L., D.F., Z.L., W.J.W., C.S.W., E.Y.L.); and Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China (E.Y.L.).
authors.forename: Lingli
authors.initials: L
authors.lastname: Li
authors.affiliation: From the Department of Medicine, Division of Nephrology and Hypertension, Hypertension, Kidney and Vascular Research Center, Georgetown University, Washington, DC (L.L., D.F., Z.L., W.J.W., C.S.W., E.Y.L.); and Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China (E.Y.L.).
authors.forename: Di
authors.initials: D
authors.lastname: Feng
authors.affiliation: From the Department of Medicine, Division of Nephrology and Hypertension, Hypertension, Kidney and Vascular Research Center, Georgetown University, Washington, DC (L.L., D.F., Z.L., W.J.W., C.S.W., E.Y.L.); and Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China (E.Y.L.).
authors.forename: Zaiming
authors.initials: Z
authors.lastname: Luo
authors.affiliation: From the Department of Medicine, Division of Nephrology and Hypertension, Hypertension, Kidney and Vascular Research Center, Georgetown University, Washington, DC (L.L., D.F., Z.L., W.J.W., C.S.W., E.Y.L.); and Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China (E.Y.L.).
authors.forename: William J
authors.initials: WJ
authors.lastname: Welch
authors.affiliation: From the Department of Medicine, Division of Nephrology and Hypertension, Hypertension, Kidney and Vascular Research Center, Georgetown University, Washington, DC (L.L., D.F., Z.L., W.J.W., C.S.W., E.Y.L.); and Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China (E.Y.L.).
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wilcox
authors.affiliation: From the Department of Medicine, Division of Nephrology and Hypertension, Hypertension, Kidney and Vascular Research Center, Georgetown University, Washington, DC (L.L., D.F., Z.L., W.J.W., C.S.W., E.Y.L.); and Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China (E.Y.L.). laienyin@zju.edu.cn.
authors.forename: En Yin
authors.initials: EY
authors.lastname: Lai
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D013314:Stress, Mechanical; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D066253:Vascular Remodeling / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D000099156:Superoxide Dismutase 2
chemical_list: D000804:Angiotensin II; D013482:Superoxide Dismutase; D013481:Superoxides; D000099156:Superoxide Dismutase 2; C499090:Sod3 protein, mouse
keywords: hypertension; oxidative stress; reactive oxygen species; superoxide dismutase; vascular remodeling