Vitamin C Deficiency Exacerbates Dysfunction of Atherosclerotic Coronary Arteries in Guinea Pigs Fed a High-Fat Diet
Vitamin C (vitC) deficiency has been associated with an increased risk of cardiovascular disease; while several putative mechanistic links have been proposed, functional evidence supporting a causal relationship is scarce. In this study, we investigated how vitC deficiency affects coronary artery va...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/11/2226 |
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| author | Gry Freja Skovsted Josephine Skat-Rørdam Amalie Pihl Frøkiær Henrik Elvang Jensen Pernille Tveden-Nyborg Jens Lykkesfeldt |
| author_facet | Gry Freja Skovsted Josephine Skat-Rørdam Amalie Pihl Frøkiær Henrik Elvang Jensen Pernille Tveden-Nyborg Jens Lykkesfeldt |
| author_sort | Gry Freja Skovsted |
| collection | DOAJ |
| description | Vitamin C (vitC) deficiency has been associated with an increased risk of cardiovascular disease; while several putative mechanistic links have been proposed, functional evidence supporting a causal relationship is scarce. In this study, we investigated how vitC deficiency affects coronary artery vasomotor function and the development of coronary atherosclerotic plaques in guinea pigs subjected to chronic dyslipidemia by a high-fat diet regime. Female Hartley guinea pigs were fed either a control (low-fat diet and sufficient vitC) (N = 8) or a high-fat diet with either sufficient (N = 8) or deficient (N = 10) vitC for 32 weeks. Guinea pigs subjected to the high-fat diet developed significant atherosclerotic plaques in their coronary arteries, with no quantitative effect of vitC deficiency. In isolated coronary arteries, vasomotor responses to potassium, carbachol, nitric oxide, or bradykinin were studied in a wire myograph. Carbachol, bradykinin, and nitric oxide mediated relaxation in the coronary arteries of the control group. While vasorelaxation to carbachol and nitric oxide was preserved in the two high-fat diet groups, bradykinin-induced vasorelaxation was abolished. Interestingly, bradykinin induced a significant contraction in coronary arteries from vitC-deficient guinea pigs (<i>p</i> < 0.05). The bradykinin-induced contraction was unaffected by L-NAME but significantly inhibited by both indomethacin and vitC, suggesting that, during vitC deficiency, increased release of arachidonic acid metabolites and vascular oxidative stress are involved in the constrictor effects mediated by bradykinin. In conclusion, the present study shows supporting evidence that poor vitC status negatively affects coronary artery function. |
| first_indexed | 2024-03-09T18:30:55Z |
| format | Article |
| id | doaj.art-1159f7e6ed2c467b965c6956356d68a6 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T18:30:55Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-1159f7e6ed2c467b965c6956356d68a62023-11-24T07:31:47ZengMDPI AGAntioxidants2076-39212022-11-011111222610.3390/antiox11112226Vitamin C Deficiency Exacerbates Dysfunction of Atherosclerotic Coronary Arteries in Guinea Pigs Fed a High-Fat DietGry Freja Skovsted0Josephine Skat-Rørdam1Amalie Pihl Frøkiær2Henrik Elvang Jensen3Pernille Tveden-Nyborg4Jens Lykkesfeldt5Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg, DenmarkSection of Experimental Animal Models, Department of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg, DenmarkSection of Experimental Animal Models, Department of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg, DenmarkSection of Pathobiological Sciences, Department of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 3, 1870 Frederiksberg, DenmarkSection of Experimental Animal Models, Department of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg, DenmarkSection of Experimental Animal Models, Department of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg, DenmarkVitamin C (vitC) deficiency has been associated with an increased risk of cardiovascular disease; while several putative mechanistic links have been proposed, functional evidence supporting a causal relationship is scarce. In this study, we investigated how vitC deficiency affects coronary artery vasomotor function and the development of coronary atherosclerotic plaques in guinea pigs subjected to chronic dyslipidemia by a high-fat diet regime. Female Hartley guinea pigs were fed either a control (low-fat diet and sufficient vitC) (N = 8) or a high-fat diet with either sufficient (N = 8) or deficient (N = 10) vitC for 32 weeks. Guinea pigs subjected to the high-fat diet developed significant atherosclerotic plaques in their coronary arteries, with no quantitative effect of vitC deficiency. In isolated coronary arteries, vasomotor responses to potassium, carbachol, nitric oxide, or bradykinin were studied in a wire myograph. Carbachol, bradykinin, and nitric oxide mediated relaxation in the coronary arteries of the control group. While vasorelaxation to carbachol and nitric oxide was preserved in the two high-fat diet groups, bradykinin-induced vasorelaxation was abolished. Interestingly, bradykinin induced a significant contraction in coronary arteries from vitC-deficient guinea pigs (<i>p</i> < 0.05). The bradykinin-induced contraction was unaffected by L-NAME but significantly inhibited by both indomethacin and vitC, suggesting that, during vitC deficiency, increased release of arachidonic acid metabolites and vascular oxidative stress are involved in the constrictor effects mediated by bradykinin. In conclusion, the present study shows supporting evidence that poor vitC status negatively affects coronary artery function.https://www.mdpi.com/2076-3921/11/11/2226vitamin Catherosclerosiscoronary arteriesguinea pig modelwire myography |
| spellingShingle | Gry Freja Skovsted Josephine Skat-Rørdam Amalie Pihl Frøkiær Henrik Elvang Jensen Pernille Tveden-Nyborg Jens Lykkesfeldt Vitamin C Deficiency Exacerbates Dysfunction of Atherosclerotic Coronary Arteries in Guinea Pigs Fed a High-Fat Diet Antioxidants vitamin C atherosclerosis coronary arteries guinea pig model wire myography |
| title | Vitamin C Deficiency Exacerbates Dysfunction of Atherosclerotic Coronary Arteries in Guinea Pigs Fed a High-Fat Diet |
| title_full | Vitamin C Deficiency Exacerbates Dysfunction of Atherosclerotic Coronary Arteries in Guinea Pigs Fed a High-Fat Diet |
| title_fullStr | Vitamin C Deficiency Exacerbates Dysfunction of Atherosclerotic Coronary Arteries in Guinea Pigs Fed a High-Fat Diet |
| title_full_unstemmed | Vitamin C Deficiency Exacerbates Dysfunction of Atherosclerotic Coronary Arteries in Guinea Pigs Fed a High-Fat Diet |
| title_short | Vitamin C Deficiency Exacerbates Dysfunction of Atherosclerotic Coronary Arteries in Guinea Pigs Fed a High-Fat Diet |
| title_sort | vitamin c deficiency exacerbates dysfunction of atherosclerotic coronary arteries in guinea pigs fed a high fat diet |
| topic | vitamin C atherosclerosis coronary arteries guinea pig model wire myography |
| url | https://www.mdpi.com/2076-3921/11/11/2226 |
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