Li Lingli, Feng Di, Luo Zaiming, Welch William J, Wilcox Christopher S, Lai En Yin
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.).
Hypertension. 2015 Sep;66(3):550-6. doi: 10.1161/HYPERTENSIONAHA.115.05631. Epub 2015 Jun 22.
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.
由于超氧化物歧化酶（SOD）基因敲除会增强小动脉重塑和收缩性，我们推测重塑会增强收缩性。在来自SOD野生型（+/+）和基因敲除小鼠的离体灌注肾传入小动脉中，通过测量灌注压力从40至80 mmHg时管腔直径的减小（肌源性反应）或血管紧张素II（10(-6) mol/L）刺激后的减小来评估收缩性，通过中膜与管腔面积比评估重塑，通过荧光显微镜评估超氧化物（O2 (·-)）和过氧化氢（H2O2），并通过壁张力/壁厚评估壁应力。与+/+品系相比，SOD1-/-、SOD2+/-和SOD3-/-小鼠的小动脉在灌注压力和血管紧张素II刺激下产生的O2 (·-)显著增多（P<0.05），肌源性反应显著增强（SOD1-/-：-20.7±2.2%对-12.7±1.6%；SOD2+/-：-7.4±1.3%对-12.6±1.4%；SOD3-/-：-9.1±1.9%对-15.8±2.2%），血管紧张素II收缩反应增强，中膜与管腔面积比增加约2倍。中膜与管腔面积比与肌源性反应（r(2) =0.23；P<0.01）、血管紧张素II收缩反应（r(2)=0.57；P<0.0001）和主动壁张力（r(2) =0.19；P<0.01）相关，但与主动壁应力无关（r(2)=0.08；无显著性差异）。浴槽中添加SOD可消除SOD3小鼠之间肌源性反应的差异，且在诱导SOD3基因敲除3天后肌源性反应增强（-26.9±1.7%对-20.1±0.7%；P<0.05），尽管中膜与管腔面积比未改变（2.01±0.09对2.02±0.03；无显著性差异）。我们得出结论，胞质、线粒体或细胞外的O2 (·-)会增强传入小动脉的收缩性和重塑。虽然重塑不会增强收缩性，但它确实能防止壁应力增加带来的潜在损害作用。
