Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the Na<sup>+</sup>, K<sup>+</sup>-ATPase α<sub>2</sub>-Isoform
Heterozygous mice (α<sub>2</sub><sup>+/G301R</sup> mice) for the migraine-associated mutation (G301R) in the Na<sup>+</sup>,K<sup>+</sup>-ATPase α<sub>2</sub>-isoform have decreased expression of cardiovascular α<sub>2</sub>-iso...
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| Formato: | Artículo |
| Lenguaje: | English |
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MDPI AG
2023-01-01
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| Colección: | Biomedicines |
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| Acceso en línea: | https://www.mdpi.com/2227-9059/11/2/344 |
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| author | Rajkumar Rajanathan Tina Myhre Pedersen Halvor Osterby Guldbrandsen Lenette Foldager Olesen Morten B. Thomsen Hans Erik Bøtker Vladimir V. Matchkov |
| author_facet | Rajkumar Rajanathan Tina Myhre Pedersen Halvor Osterby Guldbrandsen Lenette Foldager Olesen Morten B. Thomsen Hans Erik Bøtker Vladimir V. Matchkov |
| author_sort | Rajkumar Rajanathan |
| collection | DOAJ |
| description | Heterozygous mice (α<sub>2</sub><sup>+/G301R</sup> mice) for the migraine-associated mutation (G301R) in the Na<sup>+</sup>,K<sup>+</sup>-ATPase α<sub>2</sub>-isoform have decreased expression of cardiovascular α<sub>2</sub>-isoform. The α<sub>2</sub><sup>+/G301R</sup> mice exhibit a pro-contractile vascular phenotype associated with decreased left ventricular ejection fraction. However, the integrated functional cardiovascular consequences of this phenotype remain to be addressed in vivo. We hypothesized that the vascular response to α<sub>2</sub>-isoform-specific inhibition of the Na<sup>+</sup>,K<sup>+</sup>-ATPase by ouabain is augmented in α<sub>2</sub><sup>+/G301R</sup> mice leading to reduced cardiac efficiency. Thus, we aimed to assess the functional contribution of the α<sub>2</sub>-isoform to in vivo cardiovascular function of wild-type (WT) and α<sub>2</sub><sup>+/G301R</sup> mice. Blood pressure, stroke volume, heart rate, total peripheral resistance, arterial dP/dt, and systolic time intervals were assessed in anesthetized WT and α<sub>2</sub><sup>+/G301R</sup> mice. To address rate-dependent cardiac changes, cardiovascular variables were compared before and after intraperitoneal injection of ouabain (1.5 mg/kg) or vehicle during atrial pacing. The α<sub>2</sub><sup>+/G301R</sup> mice showed an enhanced ouabain-induced increase in total peripheral resistance associated with reduced efficiency of systolic development compared to WT. When the hearts were paced, ouabain reduced stroke volume in α<sub>2</sub><sup>+/G301R</sup> mice. In conclusion, the ouabain-induced vascular response was augmented in α<sub>2</sub><sup>+/G301R</sup> mice with consequent suppression of cardiac function. |
| first_indexed | 2024-03-11T09:06:44Z |
| format | Article |
| id | doaj.art-2eec613c5ccb45259ca1f9314989d331 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:06:44Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-2eec613c5ccb45259ca1f9314989d3312023-11-16T19:16:50ZengMDPI AGBiomedicines2227-90592023-01-0111234410.3390/biomedicines11020344Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the Na<sup>+</sup>, K<sup>+</sup>-ATPase α<sub>2</sub>-IsoformRajkumar Rajanathan0Tina Myhre Pedersen1Halvor Osterby Guldbrandsen2Lenette Foldager Olesen3Morten B. Thomsen4Hans Erik Bøtker5Vladimir V. Matchkov6Department of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, 1165 Copenhagen, DenmarkDepartment of Cardiology, Aarhus University Hospital, 8000 Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkHeterozygous mice (α<sub>2</sub><sup>+/G301R</sup> mice) for the migraine-associated mutation (G301R) in the Na<sup>+</sup>,K<sup>+</sup>-ATPase α<sub>2</sub>-isoform have decreased expression of cardiovascular α<sub>2</sub>-isoform. The α<sub>2</sub><sup>+/G301R</sup> mice exhibit a pro-contractile vascular phenotype associated with decreased left ventricular ejection fraction. However, the integrated functional cardiovascular consequences of this phenotype remain to be addressed in vivo. We hypothesized that the vascular response to α<sub>2</sub>-isoform-specific inhibition of the Na<sup>+</sup>,K<sup>+</sup>-ATPase by ouabain is augmented in α<sub>2</sub><sup>+/G301R</sup> mice leading to reduced cardiac efficiency. Thus, we aimed to assess the functional contribution of the α<sub>2</sub>-isoform to in vivo cardiovascular function of wild-type (WT) and α<sub>2</sub><sup>+/G301R</sup> mice. Blood pressure, stroke volume, heart rate, total peripheral resistance, arterial dP/dt, and systolic time intervals were assessed in anesthetized WT and α<sub>2</sub><sup>+/G301R</sup> mice. To address rate-dependent cardiac changes, cardiovascular variables were compared before and after intraperitoneal injection of ouabain (1.5 mg/kg) or vehicle during atrial pacing. The α<sub>2</sub><sup>+/G301R</sup> mice showed an enhanced ouabain-induced increase in total peripheral resistance associated with reduced efficiency of systolic development compared to WT. When the hearts were paced, ouabain reduced stroke volume in α<sub>2</sub><sup>+/G301R</sup> mice. In conclusion, the ouabain-induced vascular response was augmented in α<sub>2</sub><sup>+/G301R</sup> mice with consequent suppression of cardiac function.https://www.mdpi.com/2227-9059/11/2/344ouabainhemodynamicmigrainecardiovascular functionin vivocardiac pacing |
| spellingShingle | Rajkumar Rajanathan Tina Myhre Pedersen Halvor Osterby Guldbrandsen Lenette Foldager Olesen Morten B. Thomsen Hans Erik Bøtker Vladimir V. Matchkov Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the Na<sup>+</sup>, K<sup>+</sup>-ATPase α<sub>2</sub>-Isoform Biomedicines ouabain hemodynamic migraine cardiovascular function in vivo cardiac pacing |
| title | Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the Na<sup>+</sup>, K<sup>+</sup>-ATPase α<sub>2</sub>-Isoform |
| title_full | Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the Na<sup>+</sup>, K<sup>+</sup>-ATPase α<sub>2</sub>-Isoform |
| title_fullStr | Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the Na<sup>+</sup>, K<sup>+</sup>-ATPase α<sub>2</sub>-Isoform |
| title_full_unstemmed | Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the Na<sup>+</sup>, K<sup>+</sup>-ATPase α<sub>2</sub>-Isoform |
| title_short | Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the Na<sup>+</sup>, K<sup>+</sup>-ATPase α<sub>2</sub>-Isoform |
| title_sort | augmented ouabain induced vascular response reduces cardiac efficiency in mice with migraine associated mutation in the na sup sup k sup sup atpase α sub 2 sub isoform |
| topic | ouabain hemodynamic migraine cardiovascular function in vivo cardiac pacing |
| url | https://www.mdpi.com/2227-9059/11/2/344 |
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