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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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BH4 supplementation or superoxide scavenging improved vasodilation in obese mice. A, BH4 precursor sepiapterin preincubation improved acetylcholine‐induced dilation in obese mice. This improvement was blocked by l‐NAME. B, DHFR mRNA expression in mesenteric artery. C, GCH1 mRNA expression in mesenteric artery. Relative gene expression levels were quantified using the 2‐ΔΔCt approximation method. Gene expression was normalized twice to a control sample that was additionally normalized to GAPDH. The data are given as the mean±SEM. A through C, n≥6. #P<0.05, vessels incubated with versus without sepiapterin; *P<0.05; **P<0.01, vessels incubated with sepiapterin versus vessels incubated sepiapterin and l‐NAME. BH4 indicates tetrahydrobiopterin; db/db myostatin−/−, mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; DHFR, dihydrofolate reductase; GCH1, GTP cyclohydrolase I; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; l‐NAME, Nω‐nitro‐l‐arginine methyl ester.
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fig12: BH4 supplementation or superoxide scavenging improved vasodilation in obese mice. A, BH4 precursor sepiapterin preincubation improved acetylcholine‐induced dilation in obese mice. This improvement was blocked by l‐NAME. B, DHFR mRNA expression in mesenteric artery. C, GCH1 mRNA expression in mesenteric artery. Relative gene expression levels were quantified using the 2‐ΔΔCt approximation method. Gene expression was normalized twice to a control sample that was additionally normalized to GAPDH. The data are given as the mean±SEM. A through C, n≥6. #P<0.05, vessels incubated with versus without sepiapterin; *P<0.05; **P<0.01, vessels incubated with sepiapterin versus vessels incubated sepiapterin and l‐NAME. BH4 indicates tetrahydrobiopterin; db/db myostatin−/−, mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; DHFR, dihydrofolate reductase; GCH1, GTP cyclohydrolase I; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; l‐NAME, Nω‐nitro‐l‐arginine methyl ester.

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)

BH4 supplementation or superoxide scavenging improved vasodilation in obese mice. A, BH4 precursor sepiapterin preincubation improved acetylcholine‐induced dilation in obese mice. This improvement was blocked by l‐NAME. B, DHFR mRNA expression in mesenteric artery. C, GCH1 mRNA expression in mesenteric artery. Relative gene expression levels were quantified using the 2‐ΔΔCt approximation method. Gene expression was normalized twice to a control sample that was additionally normalized to GAPDH. The data are given as the mean±SEM. A through C, n≥6. #P<0.05, vessels incubated with versus without sepiapterin; *P<0.05; **P<0.01, vessels incubated with sepiapterin versus vessels incubated sepiapterin and l‐NAME. BH4 indicates tetrahydrobiopterin; db/db myostatin−/−, mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; DHFR, dihydrofolate reductase; GCH1, GTP cyclohydrolase I; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; l‐NAME, Nω‐nitro‐l‐arginine methyl ester.
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Related In: Results  -  Collection

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fig12: BH4 supplementation or superoxide scavenging improved vasodilation in obese mice. A, BH4 precursor sepiapterin preincubation improved acetylcholine‐induced dilation in obese mice. This improvement was blocked by l‐NAME. B, DHFR mRNA expression in mesenteric artery. C, GCH1 mRNA expression in mesenteric artery. Relative gene expression levels were quantified using the 2‐ΔΔCt approximation method. Gene expression was normalized twice to a control sample that was additionally normalized to GAPDH. The data are given as the mean±SEM. A through C, n≥6. #P<0.05, vessels incubated with versus without sepiapterin; *P<0.05; **P<0.01, vessels incubated with sepiapterin versus vessels incubated sepiapterin and l‐NAME. BH4 indicates tetrahydrobiopterin; db/db myostatin−/−, mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; DHFR, dihydrofolate reductase; GCH1, GTP cyclohydrolase I; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; l‐NAME, Nω‐nitro‐l‐arginine methyl ester.
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.).

Show MeSH
Related in: MedlinePlus