Abstract 539: Remodeling Of Afferent Arterioles From Mice With Oxidative Stress Does Not Enhance Contractility But Does Limit Excessive Wall Stress

Abstract

Background: Remodeling of resistant vessels in hypertension is postulated to enhance their contractility. We showed that knockout of SOD increased superoxide (O 2 .- ), contractility and remodeling of afferent arterioles (Affs). Therefore, we tested the hypothesis that the remodeling causes the enhanced contractility. Methods: Myogenic responses (MRs) were assessed from the slope of the regression of active wall tension (AWT) on perfusion pressure (PP) in wild type and knockout SOD-1,-2 or -3 mice and in mice 3 days after induction of SOD-3 knockout before remodeling had developed. Contractions to 10 -6 M Ang II were tested also. O 2 .- was assessed from PEG-SOD inhibitable ethidium:dihydroethidium fluorescence and remodeling from media:lumen area ratio (M:L). Results: 1. Compared to +/+, increasing PP or 10 -6 M Ang II increased O 2 .- of Affs more in SOD1-/-, SOD2+/- and SOD3-/- (P<0.01). 2. Compared to +/+, MRs (dynes.cm -1 .mmHg -1 ) were significantly (P<0.05) increased in SOD1-/- (3.49 ± 0.30 vs 2.30 ± 0.27), in SOD2+/- (3.85 ± 0.48 vs 1.80 ± 0.34), and in SOD3-/- (3.51 ± 0.20 vs 2.43 ± 0.15). 3. Compared to +/+, Ang II contractions were also stronger in knockout mice (P<0.001). 4. Compared to +/+, M:L ratio of Affs were significantly (P<0.001) greater in SOD1-/- (4.0 ± 0.2 vs 1.8 ± 0.2), in SOD2+/- (3.7 ± 0.4 vs 1.8 ± 0.4), and in SOD3-/- (4.5 ± 0.2 vs 1.9 ± 0.1). 5. Across genotypes, MR (r 2 =0.32, P<0.005) and Ang II contractions (r 2 = 0.56, P<0.005) were strongly correlated with M:L ratios. 6. Changes in AWT (T physiol - T passive ) during increase in PP were dependent on SOD genotype (P<0.01) yet changes in vessel wall stress (AWT/wall thickness) were independent (P=NS). 7. Compared to controls , MRs and Ang II contractions were increased 3 days after inducing SOD3 knockout (MR, 3.76 ± 0.55 vs 2.26 ± 0.01, P<0.05; Ang II, -66 ± 4% vs -49 ± 4%, P<0.01) and were not significantly different from SOD3-/- mice. However, the M:L ratio of these Affs was unchanged (2.0 ± 0.1 vs 1.8 ± 0.2, NS). Conclusions: lifetime increases in cytosolic, mitochondrial or extracellular O 2 .- enhances afferent arteriolar contractility and remodeling. The remodeling is not required for the enhanced contractility, but does prevent the damaging effects of increased wall stress.