L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome
Intermittent hypoxia (IH) is a landmark of obstructive sleep apnea (OSA) at the core of the cardiovascular consequences of OSA. IH triggers oxidative stress, a major underlying mechanism for elevated blood pressure (BP) and increased infarct size. L-citrulline is an amino acid that has been demonstr...
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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/2076-3921/11/12/2326 |
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| author | Bilgehan Ozcan Britanny Blachot-Minassian Stéphanie Paradis Lucile Mazière Marie Chambion-Diaz Sophie Bouyon Jean-Louis Pépin Vincent Pialoux Claire Arnaud Christophe Moinard Elise Belaidi |
| author_facet | Bilgehan Ozcan Britanny Blachot-Minassian Stéphanie Paradis Lucile Mazière Marie Chambion-Diaz Sophie Bouyon Jean-Louis Pépin Vincent Pialoux Claire Arnaud Christophe Moinard Elise Belaidi |
| author_sort | Bilgehan Ozcan |
| collection | DOAJ |
| description | Intermittent hypoxia (IH) is a landmark of obstructive sleep apnea (OSA) at the core of the cardiovascular consequences of OSA. IH triggers oxidative stress, a major underlying mechanism for elevated blood pressure (BP) and increased infarct size. L-citrulline is an amino acid that has been demonstrated to be protective of the cardiovascular system and exert pleiotropic effects. Therefore, we tested the impact of citrulline supplementation on IH-induced increase in BP and infarct size. Four groups of rats exposed to normoxia (N) or IH [14 days (d), 8 h/day, 30 s-O<sub>2</sub> 21%/30 s-O<sub>2</sub> 5%] and were supplemented or not with citrulline (1 g·kg<sup>−1</sup>·d<sup>−1</sup>). After 14 d, BP was measured, and hearts were submitted to global ischemia-reperfusion to measure infarct size. Histological and biochemical analyses were conducted on hearts and aorta to assess oxidative stress. Citrulline significantly reduced BP (–9.92%) and infarct size (–18.22%) under IH only. In the aorta, citrulline supplementation significantly decreased superoxide anion and nitrotyrosine levels under IH and abolished the IH-induced decrease in nitrite. Citrulline supplementation significantly decreased myocardial superoxide anion levels and xanthine oxidase enzyme activity under IH. Citrulline shows a cardioprotective capacity by limiting IH-induced pro-oxidant activity. Our results suggest that citrulline might represent a new pharmacological strategy in OSA patients with high cardiovascular risk. |
| first_indexed | 2024-03-09T17:24:26Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T17:24:26Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-cd505d8f91394c7bade81739a9157abe2023-11-24T12:56:08ZengMDPI AGAntioxidants2076-39212022-11-011112232610.3390/antiox11122326L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea SyndromeBilgehan Ozcan0Britanny Blachot-Minassian1Stéphanie Paradis2Lucile Mazière3Marie Chambion-Diaz4Sophie Bouyon5Jean-Louis Pépin6Vincent Pialoux7Claire Arnaud8Christophe Moinard9Elise Belaidi10Univ. Grenoble Alpes, HP2, Faculté de Pharmacie, F-38042 Grenoble, FranceUniv. Grenoble Alpes, HP2, Faculté de Pharmacie, F-38042 Grenoble, FranceUniv. Grenoble Alpes, HP2, Faculté de Pharmacie, F-38042 Grenoble, FranceUniv. Grenoble Alpes, HP2, Faculté de Pharmacie, F-38042 Grenoble, FranceUniv. Lyon, Université Claude Bernard Lyon1, Laboratoire Interuniversitaire de Biologie de la motricité, Team ATPA, Faculté de médecine Rockfeller, 69000 Lyon, FranceUniv. Grenoble Alpes, HP2, Faculté de Pharmacie, F-38042 Grenoble, FranceUniv. Grenoble Alpes, HP2, Faculté de Pharmacie, F-38042 Grenoble, FranceUniv. Lyon, Université Claude Bernard Lyon1, Laboratoire Interuniversitaire de Biologie de la motricité, Team ATPA, Faculté de médecine Rockfeller, 69000 Lyon, FranceUniv. Grenoble Alpes, HP2, Faculté de Pharmacie, F-38042 Grenoble, FranceUniversité Grenoble-Alpes, Laboratoire de Bioénergétique Fondamentale et Appliquée, INSERM U 1055, Faculté de Pharmacie, 38000 Grenoble, FranceUniv. Grenoble Alpes, HP2, Faculté de Pharmacie, F-38042 Grenoble, FranceIntermittent hypoxia (IH) is a landmark of obstructive sleep apnea (OSA) at the core of the cardiovascular consequences of OSA. IH triggers oxidative stress, a major underlying mechanism for elevated blood pressure (BP) and increased infarct size. L-citrulline is an amino acid that has been demonstrated to be protective of the cardiovascular system and exert pleiotropic effects. Therefore, we tested the impact of citrulline supplementation on IH-induced increase in BP and infarct size. Four groups of rats exposed to normoxia (N) or IH [14 days (d), 8 h/day, 30 s-O<sub>2</sub> 21%/30 s-O<sub>2</sub> 5%] and were supplemented or not with citrulline (1 g·kg<sup>−1</sup>·d<sup>−1</sup>). After 14 d, BP was measured, and hearts were submitted to global ischemia-reperfusion to measure infarct size. Histological and biochemical analyses were conducted on hearts and aorta to assess oxidative stress. Citrulline significantly reduced BP (–9.92%) and infarct size (–18.22%) under IH only. In the aorta, citrulline supplementation significantly decreased superoxide anion and nitrotyrosine levels under IH and abolished the IH-induced decrease in nitrite. Citrulline supplementation significantly decreased myocardial superoxide anion levels and xanthine oxidase enzyme activity under IH. Citrulline shows a cardioprotective capacity by limiting IH-induced pro-oxidant activity. Our results suggest that citrulline might represent a new pharmacological strategy in OSA patients with high cardiovascular risk.https://www.mdpi.com/2076-3921/11/12/2326obstructive sleep apneacitrullineintermittent hypoxiaoxidative stress |
| spellingShingle | Bilgehan Ozcan Britanny Blachot-Minassian Stéphanie Paradis Lucile Mazière Marie Chambion-Diaz Sophie Bouyon Jean-Louis Pépin Vincent Pialoux Claire Arnaud Christophe Moinard Elise Belaidi L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome Antioxidants obstructive sleep apnea citrulline intermittent hypoxia oxidative stress |
| title | L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome |
| title_full | L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome |
| title_fullStr | L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome |
| title_full_unstemmed | L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome |
| title_short | L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome |
| title_sort | l citrulline supplementation reduces blood pressure and myocardial infarct size under chronic intermittent hypoxia a major feature of sleep apnea syndrome |
| topic | obstructive sleep apnea citrulline intermittent hypoxia oxidative stress |
| url | https://www.mdpi.com/2076-3921/11/12/2326 |
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