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• W2894088045 abstract "In the vasculature, sedentary behavior leads to endothelial abnormalities, resulting in elevated cardiovascular disease risk. Endothelial nitric oxide synthase (eNOS) aberrations characterize endothelial dysfunction; eNOS also regulates mitochondrial function. We hypothesized that sepiapterin (a precursor to eNOS cofactor tetrahydrobiopterin (BH 4 )) supplementation would improve endothelium-dependent vascular relaxation in sedentary animals via modulation of NOS function and mitochondrial activity. Sedentary male Wistar rats were fed ad libitum for a total of 10 weeks. Sepiapterin was administered in diet during the final 5 weeks. Intraperitoneal insulin and glucose tolerance tests (IP-ITT/IP-GTT) were conducted at baseline and endpoint. Aorta was assessed for vasoreactivity and mitochondrial respiration. Insulin tolerance, determined by IP-ITT, significantly improved in rats treated with sepiapterin (<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M1><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>, interaction of time and treatment). Acetylcholine- (ACh-) driven vasodilation was significantly greater in aorta from sepiapterin-treated rats as compared with control (76.4% versus 54.9% of phenylephrine contraction at 20 μ M ACh, <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M2><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>). Sepiapterin treatment resulted in significantly elevated state 3 (9.00 oxygen pmol/sec<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M3><mml:msup><mml:mrow /><mml:mrow><mml:mo>∗</mml:mo></mml:mrow></mml:msup></mml:math>mg versus 8.17 oxygen pmol/sec<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M4><mml:msup><mml:mrow /><mml:mrow><mml:mo>∗</mml:mo></mml:mrow></mml:msup></mml:math>mg, <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M5><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>) and 4 (7.28 oxygen pmol/sec<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M6><mml:msup><mml:mrow /><mml:mrow><mml:mo>∗</mml:mo></mml:mrow></mml:msup></mml:math>mg versus 5.86 oxygen pmol/sec<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M7><mml:msup><mml:mrow /><mml:mrow><mml:mo>∗</mml:mo></mml:mrow></mml:msup></mml:math>mg, <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M8><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>) aortic mitochondrial respiration with significantly lower respiratory control ratio (<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M9><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>) during octanoylcarnitine-driven respiration. Vasodilation and insulin sensitivity were improved through targeting NOS via sepiapterin supplementation." @default.
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• W2894088045 date "2018-09-23" @default.
• W2894088045 modified "2023-10-16" @default.
• W2894088045 title "Sepiapterin Improves Vascular Reactivity and Insulin-Stimulated Glucose in Wistar Rats" @default.
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• W2894088045 doi "https://doi.org/10.1155/2018/7363485" @default.
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