Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling
Data indicate endothelium-dependent dilation (EDD) may be preserved in the skeletal muscle microcirculation of young, obese adults. Preserved EDD might be mediated by compensatory mechanisms, impeding insight into preclinical vascular dysfunction. We aimed to determine the functional roles of nitri...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-12-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2015.00387/full |
| _version_ | 1818671892361379840 |
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| author | John eHarrell Rebecca eJohansson Trent eEvans Joshua eSebreanek Benjamin eWalker Marlowe eEldridge Ronald eSerlin William G Schrage |
| author_facet | John eHarrell Rebecca eJohansson Trent eEvans Joshua eSebreanek Benjamin eWalker Marlowe eEldridge Ronald eSerlin William G Schrage |
| author_sort | John eHarrell |
| collection | DOAJ |
| description | Data indicate endothelium-dependent dilation (EDD) may be preserved in the skeletal muscle microcirculation of young, obese adults. Preserved EDD might be mediated by compensatory mechanisms, impeding insight into preclinical vascular dysfunction. We aimed to determine the functional roles of nitric oxide synthase (NOS) and cyclooxygenase (COX) toward EDD in younger obese adults. We first hypothesized EDD would be preserved in young, obese adults. Further, we hypothesized a reduced contribution of NOS in young, obese adults would be replaced by increased COX signaling. Microvascular EDD was assessed with Doppler ultrasound and brachial artery infusion of acetylcholine (ACh) in younger (27±1 yr) obese (n=29) and lean (n=46) humans. Individual and combined contributions of NOS and COX were examined with intra-arterial infusions of L-NMMA and ketorolac, respectively. Vasodilation was quantified as an increase in forearm vascular conductance (ΔFVC). Arterial endothelial cell biopsies were analyzed for protein expression of endothelial nitric oxide synthase (eNOS). ΔFVC to ACh was similar between groups. After L-NMMA, ΔFVC to ACh was greater in obese adults (p<0.05). There were no group differences in ΔFVC to ACh with ketorolac. With combined NOS-COX inhibition, ΔFVC was greater in obese adults at the intermediate dose of ACh. Surprisingly, arterial endothelial cell eNOS and phosphorylated eNOS were similar between groups. Younger obese adults exhibit preserved EDD and eNOS expression despite functional dissociation of NOS-mediated vasodilation and similar COX signaling. Compensatory NOS- and COX-independent vasodilatory mechanisms conceal reduced NOS contributions in otherwise healthy obese adults early in life, which may contribute to vascular dysfunction. |
| first_indexed | 2024-12-17T07:31:13Z |
| format | Article |
| id | doaj.art-ca1e8817ba7944d990ba4deeb6cc19fd |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-17T07:31:13Z |
| publishDate | 2015-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-ca1e8817ba7944d990ba4deeb6cc19fd2022-12-21T21:58:30ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2015-12-01610.3389/fphys.2015.00387172212Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signalingJohn eHarrell0Rebecca eJohansson1Trent eEvans2Joshua eSebreanek3Benjamin eWalker4Marlowe eEldridge5Ronald eSerlin6William G Schrage7University of Wisconsin-MadisonUniversity of Wisconsin-MadisonUniversity of Wisconsin-MadisonUniversity of Wisconsin-MadisonUniversity of Wisconsin-MadisonUniversity of Wisconsin-MadisonUniversity of Wisconsin-MadisonUniversity of Wisconsin-MadisonData indicate endothelium-dependent dilation (EDD) may be preserved in the skeletal muscle microcirculation of young, obese adults. Preserved EDD might be mediated by compensatory mechanisms, impeding insight into preclinical vascular dysfunction. We aimed to determine the functional roles of nitric oxide synthase (NOS) and cyclooxygenase (COX) toward EDD in younger obese adults. We first hypothesized EDD would be preserved in young, obese adults. Further, we hypothesized a reduced contribution of NOS in young, obese adults would be replaced by increased COX signaling. Microvascular EDD was assessed with Doppler ultrasound and brachial artery infusion of acetylcholine (ACh) in younger (27±1 yr) obese (n=29) and lean (n=46) humans. Individual and combined contributions of NOS and COX were examined with intra-arterial infusions of L-NMMA and ketorolac, respectively. Vasodilation was quantified as an increase in forearm vascular conductance (ΔFVC). Arterial endothelial cell biopsies were analyzed for protein expression of endothelial nitric oxide synthase (eNOS). ΔFVC to ACh was similar between groups. After L-NMMA, ΔFVC to ACh was greater in obese adults (p<0.05). There were no group differences in ΔFVC to ACh with ketorolac. With combined NOS-COX inhibition, ΔFVC was greater in obese adults at the intermediate dose of ACh. Surprisingly, arterial endothelial cell eNOS and phosphorylated eNOS were similar between groups. Younger obese adults exhibit preserved EDD and eNOS expression despite functional dissociation of NOS-mediated vasodilation and similar COX signaling. Compensatory NOS- and COX-independent vasodilatory mechanisms conceal reduced NOS contributions in otherwise healthy obese adults early in life, which may contribute to vascular dysfunction.http://journal.frontiersin.org/Journal/10.3389/fphys.2015.00387/fullEndotheliumMicrocirculationNitric Oxide SynthaseObesityVascular function |
| spellingShingle | John eHarrell Rebecca eJohansson Trent eEvans Joshua eSebreanek Benjamin eWalker Marlowe eEldridge Ronald eSerlin William G Schrage Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling Frontiers in Physiology Endothelium Microcirculation Nitric Oxide Synthase Obesity Vascular function |
| title | Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling |
| title_full | Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling |
| title_fullStr | Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling |
| title_full_unstemmed | Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling |
| title_short | Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling |
| title_sort | preserved microvascular endothelial function in young obese adults with functional loss of nitric oxide signaling |
| topic | Endothelium Microcirculation Nitric Oxide Synthase Obesity Vascular function |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2015.00387/full |
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