Knockdown of Inhibitory Guanine Nucleotide Binding Protein Giα‐2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive Rats
BackgroundWe previously showed that the levels of both Giα‐2 and Giα‐3 proteins were augmented in spontaneously hypertensive rats (SHRs) before the onset of hypertension. In addition, intraperitoneal injection of pertussis toxin, which inactivates both Giα proteins, prevented the development of hype...
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| Format: | Article |
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Wiley
2016-10-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.116.004594 |
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| author | Yousra Ali El‐Basyuni Yuan Li Madhu B. Anand‐Srivastava |
| author_facet | Yousra Ali El‐Basyuni Yuan Li Madhu B. Anand‐Srivastava |
| author_sort | Yousra Ali El‐Basyuni |
| collection | DOAJ |
| description | BackgroundWe previously showed that the levels of both Giα‐2 and Giα‐3 proteins were augmented in spontaneously hypertensive rats (SHRs) before the onset of hypertension. In addition, intraperitoneal injection of pertussis toxin, which inactivates both Giα proteins, prevented the development of hypertension in SHRs. The aim of the present study was to determine the specific contributions of Giα‐2 and Giα‐3 proteins to the development of hypertension. Methods and ResultsAntisense oligodeoxynucleotide of Giα‐2 and Giα‐3 encapsulated in PEG/DOTAP/DOPE cationic liposomes were administrated intravenously into 3‐week‐old prehypertensive SHRs and Wistar Kyoto rats, whereas the control Wistar Kyoto rats and SHRs received PBS, empty liposomes, or sense. The knockdown of Giα‐2 but not Giα‐3 protein attenuated tachycardia and prevented the development of hypertension up to age 6 weeks; thereafter, blood pressure started increasing and reached the same level as that of untreated SHRs at 9 weeks. Furthermore, Giα‐2 and Giα‐3 antisense oligodeoxynucleotide treatments significantly decreased the enhanced levels of Giα‐2 and Giα‐3 proteins, respectively, and enhanced levels of superoxide anion and NADPH oxidase activity in heart, aorta, and kidney and hyperproliferation of vascular smooth muscle cells from SHRs aged 6 weeks. In addition, antisense oligodeoxynucleotide treatment with Giα‐2 but not Giα‐3 restored enhanced inhibition of adenylyl cyclase by oxotremorine to WKY levels. ConclusionsThese results suggested that the enhanced expression of Giα‐2 but not Giα‐3 protein plays an important role in the pathogenesis of hypertension and tachycardia in SHRs. |
| first_indexed | 2024-12-22T20:48:40Z |
| format | Article |
| id | doaj.art-c8f8fbca93e54fa38ed31ee4b6801d9e |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-22T20:48:40Z |
| publishDate | 2016-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-c8f8fbca93e54fa38ed31ee4b6801d9e2022-12-21T18:13:09ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-10-0151110.1161/JAHA.116.004594Knockdown of Inhibitory Guanine Nucleotide Binding Protein Giα‐2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive RatsYousra Ali El‐Basyuni0Yuan Li1Madhu B. Anand‐Srivastava2Department of Molecular and Integrative Physiology, Faculty of Medicine, University of Montreal, Quebec, CanadaDepartment of Molecular and Integrative Physiology, Faculty of Medicine, University of Montreal, Quebec, CanadaDepartment of Molecular and Integrative Physiology, Faculty of Medicine, University of Montreal, Quebec, CanadaBackgroundWe previously showed that the levels of both Giα‐2 and Giα‐3 proteins were augmented in spontaneously hypertensive rats (SHRs) before the onset of hypertension. In addition, intraperitoneal injection of pertussis toxin, which inactivates both Giα proteins, prevented the development of hypertension in SHRs. The aim of the present study was to determine the specific contributions of Giα‐2 and Giα‐3 proteins to the development of hypertension. Methods and ResultsAntisense oligodeoxynucleotide of Giα‐2 and Giα‐3 encapsulated in PEG/DOTAP/DOPE cationic liposomes were administrated intravenously into 3‐week‐old prehypertensive SHRs and Wistar Kyoto rats, whereas the control Wistar Kyoto rats and SHRs received PBS, empty liposomes, or sense. The knockdown of Giα‐2 but not Giα‐3 protein attenuated tachycardia and prevented the development of hypertension up to age 6 weeks; thereafter, blood pressure started increasing and reached the same level as that of untreated SHRs at 9 weeks. Furthermore, Giα‐2 and Giα‐3 antisense oligodeoxynucleotide treatments significantly decreased the enhanced levels of Giα‐2 and Giα‐3 proteins, respectively, and enhanced levels of superoxide anion and NADPH oxidase activity in heart, aorta, and kidney and hyperproliferation of vascular smooth muscle cells from SHRs aged 6 weeks. In addition, antisense oligodeoxynucleotide treatment with Giα‐2 but not Giα‐3 restored enhanced inhibition of adenylyl cyclase by oxotremorine to WKY levels. ConclusionsThese results suggested that the enhanced expression of Giα‐2 but not Giα‐3 protein plays an important role in the pathogenesis of hypertension and tachycardia in SHRs.https://www.ahajournals.org/doi/10.1161/JAHA.116.004594antisenseGiα‐2 proteinsGiα‐3 proteinshypertensionoxidative stresstachycardia |
| spellingShingle | Yousra Ali El‐Basyuni Yuan Li Madhu B. Anand‐Srivastava Knockdown of Inhibitory Guanine Nucleotide Binding Protein Giα‐2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive Rats Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease antisense Giα‐2 proteins Giα‐3 proteins hypertension oxidative stress tachycardia |
| title | Knockdown of Inhibitory Guanine Nucleotide Binding Protein Giα‐2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive Rats |
| title_full | Knockdown of Inhibitory Guanine Nucleotide Binding Protein Giα‐2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive Rats |
| title_fullStr | Knockdown of Inhibitory Guanine Nucleotide Binding Protein Giα‐2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive Rats |
| title_full_unstemmed | Knockdown of Inhibitory Guanine Nucleotide Binding Protein Giα‐2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive Rats |
| title_short | Knockdown of Inhibitory Guanine Nucleotide Binding Protein Giα‐2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive Rats |
| title_sort | knockdown of inhibitory guanine nucleotide binding protein giα 2 by antisense oligodeoxynucleotides attenuates the development of hypertension and tachycardia in spontaneously hypertensive rats |
| topic | antisense Giα‐2 proteins Giα‐3 proteins hypertension oxidative stress tachycardia |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.116.004594 |
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