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Increasing muscle mass improves vascular function in obese (db/db) mice.

Qiu S, Mintz JD, Salet CD, Han W, Giannis A, Chen F, Yu Y, Su Y, Fulton DJ, Stepp DW - J Am Heart Assoc (2014)

Bottom Line: Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training.This impairment was improved by superoxide dismutase mimic Tempol.This improvement was blunted by nitric oxide (NO) synthase inhibitor l-NG-nitroarginine methyl ester (l-NAME).

View Article: PubMed Central - PubMed

Affiliation: Vascular Biology Center and Department of Physiology, Georgia Regents University, Augusta, GA, Germany (S.Q., J.D.M., C.D.S., W.H., A.G., F.C., Y.Y., Y.S., D.J.F., D.W.S.).

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NADPH oxidase 1 expression and NADPH oxidase 1 inhibition improved vasodilation in obese mice. A, Representative blot of expression of NOX 1 in mesenteric arteries determined by Western blot with Hsp90 was used as a loading control. B, Quantification of NOX1 protein expression by 1‐way ANOVA. C, Confocal microscopy assessed localization of NOX1 in mesenteric arteries. D, Inhibition of NOX by GKT136901 restored impaired vasodilation in db/db mice. B, *P<0.05, lean versus lean myostatin−/− or db/db versus db/db myostatin−/−; #P<0.05, lean versus db/db or lean myostatin−/− versus db/db myostatin−/−. D, ***P<0.001, Vessels incubated with GKT 136901 versus vessels incubated without GKT136901. The data are given as the mean±SEM (A through D: n=6 to 8). ANOVA indicates analysis of variance; db/db myostatin−/−, mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; NADPH, nicotinamide adenine dinucleotide phosphate; NOX, NADPH oxidase 1.
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fig11: NADPH oxidase 1 expression and NADPH oxidase 1 inhibition improved vasodilation in obese mice. A, Representative blot of expression of NOX 1 in mesenteric arteries determined by Western blot with Hsp90 was used as a loading control. B, Quantification of NOX1 protein expression by 1‐way ANOVA. C, Confocal microscopy assessed localization of NOX1 in mesenteric arteries. D, Inhibition of NOX by GKT136901 restored impaired vasodilation in db/db mice. B, *P<0.05, lean versus lean myostatin−/− or db/db versus db/db myostatin−/−; #P<0.05, lean versus db/db or lean myostatin−/− versus db/db myostatin−/−. D, ***P<0.001, Vessels incubated with GKT 136901 versus vessels incubated without GKT136901. The data are given as the mean±SEM (A through D: n=6 to 8). ANOVA indicates analysis of variance; db/db myostatin−/−, mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; NADPH, nicotinamide adenine dinucleotide phosphate; NOX, NADPH oxidase 1.

Mentions: All data are reported as means±SEM, with “n” representing the number of mice used in each of the experimental groups. Concentration‐response curves from isolated mesenteric arteries (Figures 7 and 8) were computer fitted to a sigmoidal curve using nonlinear regression (Prism version 5.0; GraphPad Software Inc., San Diego, CA). Maximum vessel relaxation to agonists (Figures 7D, 10A, 11D, and 12A) was measured as a percentage of preconstriction to PE and was analyzed using a multivariable regression analysis in NCSS software (NCSS, LLC, Kaysville, UT). Figure 1A was analyzed using a 1‐way ANOVA and Tukey's multiple comparisons to test myostatin mRNA level difference among different tissues. In Figure 8A through 8D, results were ranked and a 2‐way ANOVA was performed on the ranks. There were 3‐full‐model repeated‐measures analyses. All 3 used the same 2 between factors, which were factor 1 (lean versus obese) and factor 2 (with versus without myostation). For GTT results (Figure 6), the within factor was time. For vessel response curves (Figure 7), the one within factor was different doses ranging from 10−9 to 10−4 mol/L. For the passive mechanical measurements (Figure 13), within factor was pressure. All 3 full‐model repeated‐measures ANOVA were performed using the NCSS software. All remaining experiments were analyzed using a 2‐way ANOVA with Bonferroni's multiple comparisons test. The 2 factors in the 2‐way ANOVA was factor 1 (lean versus obese) and factor 2 (with versus without myostation). Figure 8A through 8D was analyzed using nonparametric repeated measurement. For all analyses, statistical significance was accepted at P<0.05.


Increasing muscle mass improves vascular function in obese (db/db) mice.

Qiu S, Mintz JD, Salet CD, Han W, Giannis A, Chen F, Yu Y, Su Y, Fulton DJ, Stepp DW - J Am Heart Assoc (2014)

NADPH oxidase 1 expression and NADPH oxidase 1 inhibition improved vasodilation in obese mice. A, Representative blot of expression of NOX 1 in mesenteric arteries determined by Western blot with Hsp90 was used as a loading control. B, Quantification of NOX1 protein expression by 1‐way ANOVA. C, Confocal microscopy assessed localization of NOX1 in mesenteric arteries. D, Inhibition of NOX by GKT136901 restored impaired vasodilation in db/db mice. B, *P<0.05, lean versus lean myostatin−/− or db/db versus db/db myostatin−/−; #P<0.05, lean versus db/db or lean myostatin−/− versus db/db myostatin−/−. D, ***P<0.001, Vessels incubated with GKT 136901 versus vessels incubated without GKT136901. The data are given as the mean±SEM (A through D: n=6 to 8). ANOVA indicates analysis of variance; db/db myostatin−/−, mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; NADPH, nicotinamide adenine dinucleotide phosphate; NOX, NADPH oxidase 1.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4309080&req=5

fig11: NADPH oxidase 1 expression and NADPH oxidase 1 inhibition improved vasodilation in obese mice. A, Representative blot of expression of NOX 1 in mesenteric arteries determined by Western blot with Hsp90 was used as a loading control. B, Quantification of NOX1 protein expression by 1‐way ANOVA. C, Confocal microscopy assessed localization of NOX1 in mesenteric arteries. D, Inhibition of NOX by GKT136901 restored impaired vasodilation in db/db mice. B, *P<0.05, lean versus lean myostatin−/− or db/db versus db/db myostatin−/−; #P<0.05, lean versus db/db or lean myostatin−/− versus db/db myostatin−/−. D, ***P<0.001, Vessels incubated with GKT 136901 versus vessels incubated without GKT136901. The data are given as the mean±SEM (A through D: n=6 to 8). ANOVA indicates analysis of variance; db/db myostatin−/−, mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; NADPH, nicotinamide adenine dinucleotide phosphate; NOX, NADPH oxidase 1.
Mentions: All data are reported as means±SEM, with “n” representing the number of mice used in each of the experimental groups. Concentration‐response curves from isolated mesenteric arteries (Figures 7 and 8) were computer fitted to a sigmoidal curve using nonlinear regression (Prism version 5.0; GraphPad Software Inc., San Diego, CA). Maximum vessel relaxation to agonists (Figures 7D, 10A, 11D, and 12A) was measured as a percentage of preconstriction to PE and was analyzed using a multivariable regression analysis in NCSS software (NCSS, LLC, Kaysville, UT). Figure 1A was analyzed using a 1‐way ANOVA and Tukey's multiple comparisons to test myostatin mRNA level difference among different tissues. In Figure 8A through 8D, results were ranked and a 2‐way ANOVA was performed on the ranks. There were 3‐full‐model repeated‐measures analyses. All 3 used the same 2 between factors, which were factor 1 (lean versus obese) and factor 2 (with versus without myostation). For GTT results (Figure 6), the within factor was time. For vessel response curves (Figure 7), the one within factor was different doses ranging from 10−9 to 10−4 mol/L. For the passive mechanical measurements (Figure 13), within factor was pressure. All 3 full‐model repeated‐measures ANOVA were performed using the NCSS software. All remaining experiments were analyzed using a 2‐way ANOVA with Bonferroni's multiple comparisons test. The 2 factors in the 2‐way ANOVA was factor 1 (lean versus obese) and factor 2 (with versus without myostation). Figure 8A through 8D was analyzed using nonparametric repeated measurement. For all analyses, statistical significance was accepted at P<0.05.

Bottom Line: Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training.This impairment was improved by superoxide dismutase mimic Tempol.This improvement was blunted by nitric oxide (NO) synthase inhibitor l-NG-nitroarginine methyl ester (l-NAME).

View Article: PubMed Central - PubMed

Affiliation: Vascular Biology Center and Department of Physiology, Georgia Regents University, Augusta, GA, Germany (S.Q., J.D.M., C.D.S., W.H., A.G., F.C., Y.Y., Y.S., D.J.F., D.W.S.).

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Related in: MedlinePlus