Figure 12.

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‐null mice heterozygous for leptin receptors; lean, lean dual heterozygotes; l‐NAME, N^ω‐nitro‐l‐arginine methyl ester.