Remodeling of Afferent Arterioles From Mice With Oxidative Stress Does Not Account for Increased Contractility but Does Limit Excessive Wall Stress. Issue 3 (September 2015)

• Record Type: Journal Article
• Authors: Li, Lingli; Feng, Di; Luo, Zaiming; Welch, William J.; Wilcox, Christopher S.; Lai, En Yin
• Is Part Of: Hypertension. Volume 66:Issue 3(2015:Sep.)
• Publication Date: 2015-09
• Subjects: Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.115.05631
• Languages: English
• ISSNs: 0194-911X

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>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<sup>–6</sup> mol/L), remodeling from media:lumen area ratio, superoxide (O<sub>2</sub><sup>·−</sup>) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) from fluorescence microscopy, and wall stress from wall tension/wall thickness. Compared with +/+ strains, arterioles from SOD1−/−, SOD2+/−, and SOD3−/− mice developed significantly (<italic>P</italic><0.05) more O<sub>2</sub><sup>·−</sup> 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 (<italic>r</italic><sup>2</sup> =0.23; <italic>P</italic><0.01), angiotensin II contractions (<italic>r</italic><sup>2</sup>=0.57; <italic>P</italic><0.0001), and active wall tension (<italic>r</italic><sup>2</sup> =0.19; <italic>P</italic><0.01), but not with active wall stress (<italic>r</italic><sup>2</sup>=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%; <italic>P</italic><0.05), despite unchanged media:lumen ratios (2.01±0.09 versus 2.02±0.03; NS). We conclude that cytosolic, mitochondrial, or extracellular O<sub>2</sub><sup>·−</sup> enhance afferent arteriolar contractility and remodeling. Although remodeling does not enhance contractility, it does prevent the potentially damaging effects of increased wall stress.</p> </sec> </abstract>