Decreased EDHF‐mediated relaxation is a major mechanism in endothelial dysfunction in resistance arteries in aged mice on prolonged high‐fat sucrose diet
Abstract High‐fat sucrose (HFS) diet in aged individuals causes severe weight gain (obesity) with much higher risk of cardiovascular diseases such as hypertension or atherosclerosis. Endothelial dysfunction is a major contributor for these vascular disorders. We hypothesize that prolonged ingestion...
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| Format: | Article |
| Language: | English |
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Wiley
2017-12-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.13502 |
| _version_ | 1818275392723615744 |
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| author | Shannon M. Dunn Robert H. P. Hilgers Kumuda C. Das |
| author_facet | Shannon M. Dunn Robert H. P. Hilgers Kumuda C. Das |
| author_sort | Shannon M. Dunn |
| collection | DOAJ |
| description | Abstract High‐fat sucrose (HFS) diet in aged individuals causes severe weight gain (obesity) with much higher risk of cardiovascular diseases such as hypertension or atherosclerosis. Endothelial dysfunction is a major contributor for these vascular disorders. We hypothesize that prolonged ingestion of HFS diet by aged mice would accentuate endothelial dysfunction in the small resistance arteries. Male C57BL/6J mice at 12 weeks of age were divided into four groups and fed either normal chow (NC) or high‐fat sucrose diet (HFS). Young group received NC for 4 months, and high‐fat diet (HFD) for 3 months and 1 month HFS + 10% Sucrose (HFS diet). Aged mice received NC for 12 months. Aged HFS group received HFD for 4 months + 1 month HFD + 10% sucrose + 8 months HFD. Total body weight, plasma blood glucose levels, and glucose tolerance were determined in all groups. Isolated mesenteric arteries were assessed for arterial remodeling, myogenic tone, and vasomotor responses using pressure and wire myography. Both young and aged HFS mice showed impaired glucose tolerance (Y‐NC, 137 ± 8.5 vs. Y‐NC HFS, 228 ± 11.71; A‐NC, 148 ± 6.42 vs. A‐HFS, 225 ± 10.99), as well as hypercholesterolemia (Y‐NC 99.50 ± 6.35 vs. Y‐HFS 220.40 ± 16.34 mg/dL; A‐NC 108.6 ± vs. A‐HFS 279 ± 21.64) and significant weight gain (Y‐NC 32.13 ± 0.8 g vs. Y‐HFS 47.87 ± 2.18 g; A‐NC 33.72 vs. A‐HFS 56.28 ± 3.47 g) compared to both groups of mice on NC. The mesenteric artery from mice with prolonged HFS diet resulted in outward hypertrophic remodeling, increased stiffness, reduced myogenic tone, impaired vasodilation, increased contractility and blunted nitric oxide (NO) and EDH‐mediated relaxations. Ebselen, a peroxinitrite scavenger rescued the endothelium derived relaxing factor (EDHF)‐mediated relaxations. Our findings suggest that prolonged diet‐induced obesity of aged mice can worsen small resistance artery endothelial dysfunction due to decrease in NO and EDHF‐mediated relaxation, but, EDHF‐mediated relaxation is a major contributor to overall endothelial dysfunction. |
| first_indexed | 2024-12-12T22:29:02Z |
| format | Article |
| id | doaj.art-c81b961f895f44de9e4e891113cbb702 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-12-12T22:29:02Z |
| publishDate | 2017-12-01 |
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| series | Physiological Reports |
| spelling | doaj.art-c81b961f895f44de9e4e891113cbb7022022-12-22T00:09:40ZengWileyPhysiological Reports2051-817X2017-12-01523n/an/a10.14814/phy2.13502Decreased EDHF‐mediated relaxation is a major mechanism in endothelial dysfunction in resistance arteries in aged mice on prolonged high‐fat sucrose dietShannon M. Dunn0Robert H. P. Hilgers1Kumuda C. Das2Department of Pharmacology & Neuroscience Texas Tech University Health Sciences Center Lubbock TexasThe Department of Translational & Vascular Biology University of Texas Health Sciences Center at Tyler Tyler TexasThe Department of Translational & Vascular Biology University of Texas Health Sciences Center at Tyler Tyler TexasAbstract High‐fat sucrose (HFS) diet in aged individuals causes severe weight gain (obesity) with much higher risk of cardiovascular diseases such as hypertension or atherosclerosis. Endothelial dysfunction is a major contributor for these vascular disorders. We hypothesize that prolonged ingestion of HFS diet by aged mice would accentuate endothelial dysfunction in the small resistance arteries. Male C57BL/6J mice at 12 weeks of age were divided into four groups and fed either normal chow (NC) or high‐fat sucrose diet (HFS). Young group received NC for 4 months, and high‐fat diet (HFD) for 3 months and 1 month HFS + 10% Sucrose (HFS diet). Aged mice received NC for 12 months. Aged HFS group received HFD for 4 months + 1 month HFD + 10% sucrose + 8 months HFD. Total body weight, plasma blood glucose levels, and glucose tolerance were determined in all groups. Isolated mesenteric arteries were assessed for arterial remodeling, myogenic tone, and vasomotor responses using pressure and wire myography. Both young and aged HFS mice showed impaired glucose tolerance (Y‐NC, 137 ± 8.5 vs. Y‐NC HFS, 228 ± 11.71; A‐NC, 148 ± 6.42 vs. A‐HFS, 225 ± 10.99), as well as hypercholesterolemia (Y‐NC 99.50 ± 6.35 vs. Y‐HFS 220.40 ± 16.34 mg/dL; A‐NC 108.6 ± vs. A‐HFS 279 ± 21.64) and significant weight gain (Y‐NC 32.13 ± 0.8 g vs. Y‐HFS 47.87 ± 2.18 g; A‐NC 33.72 vs. A‐HFS 56.28 ± 3.47 g) compared to both groups of mice on NC. The mesenteric artery from mice with prolonged HFS diet resulted in outward hypertrophic remodeling, increased stiffness, reduced myogenic tone, impaired vasodilation, increased contractility and blunted nitric oxide (NO) and EDH‐mediated relaxations. Ebselen, a peroxinitrite scavenger rescued the endothelium derived relaxing factor (EDHF)‐mediated relaxations. Our findings suggest that prolonged diet‐induced obesity of aged mice can worsen small resistance artery endothelial dysfunction due to decrease in NO and EDHF‐mediated relaxation, but, EDHF‐mediated relaxation is a major contributor to overall endothelial dysfunction.https://doi.org/10.14814/phy2.13502Agingendothelial dysfunctionendothelium‐dependent hyperpolarizing factorhigh‐fat sucrose dietobesityperoxinitrite |
| spellingShingle | Shannon M. Dunn Robert H. P. Hilgers Kumuda C. Das Decreased EDHF‐mediated relaxation is a major mechanism in endothelial dysfunction in resistance arteries in aged mice on prolonged high‐fat sucrose diet Physiological Reports Aging endothelial dysfunction endothelium‐dependent hyperpolarizing factor high‐fat sucrose diet obesity peroxinitrite |
| title | Decreased EDHF‐mediated relaxation is a major mechanism in endothelial dysfunction in resistance arteries in aged mice on prolonged high‐fat sucrose diet |
| title_full | Decreased EDHF‐mediated relaxation is a major mechanism in endothelial dysfunction in resistance arteries in aged mice on prolonged high‐fat sucrose diet |
| title_fullStr | Decreased EDHF‐mediated relaxation is a major mechanism in endothelial dysfunction in resistance arteries in aged mice on prolonged high‐fat sucrose diet |
| title_full_unstemmed | Decreased EDHF‐mediated relaxation is a major mechanism in endothelial dysfunction in resistance arteries in aged mice on prolonged high‐fat sucrose diet |
| title_short | Decreased EDHF‐mediated relaxation is a major mechanism in endothelial dysfunction in resistance arteries in aged mice on prolonged high‐fat sucrose diet |
| title_sort | decreased edhf mediated relaxation is a major mechanism in endothelial dysfunction in resistance arteries in aged mice on prolonged high fat sucrose diet |
| topic | Aging endothelial dysfunction endothelium‐dependent hyperpolarizing factor high‐fat sucrose diet obesity peroxinitrite |
| url | https://doi.org/10.14814/phy2.13502 |
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