The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7) Analogue Cyclic Ang-(1–7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction
Modulation of renin-angiotensin system (RAS) by angiotensin-(1–7) (Ang-(1–7)) is an attractive approach to combat the detrimental consequences of myocardial infarction (MI). However Ang-(1–7) has limited clinical potential due to its unfavorable pharmacokinetic profile. We investigated effects of a...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Hypertension |
| Online Access: | http://dx.doi.org/10.1155/2012/536426 |
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| author | Matej Durik Richard van Veghel Anneke Kuipers Rick Rink Marijke Haas Jimoh Akanbi Gert Moll A. H. Jan Danser Anton J. M. Roks |
| author_facet | Matej Durik Richard van Veghel Anneke Kuipers Rick Rink Marijke Haas Jimoh Akanbi Gert Moll A. H. Jan Danser Anton J. M. Roks |
| author_sort | Matej Durik |
| collection | DOAJ |
| description | Modulation of renin-angiotensin system (RAS) by angiotensin-(1–7) (Ang-(1–7)) is an attractive approach to combat the detrimental consequences of myocardial infarction (MI). However Ang-(1–7) has limited clinical potential due to its unfavorable pharmacokinetic profile. We investigated effects of a stabilized, thioether-bridged analogue of Ang-(1–7) called cyclic Ang-(1–7) in rat model of myocardial infarction. Rats underwent coronary ligation or sham surgery. Two weeks thereafter infusion with 0.24 or 2.4 μg/kg/h cAng-(1–7) or saline was started for 8 weeks. Thereafter, cardiac morphometric and hemodynamic variables as wells as aortic endothelial function were measured.
The average infarct size was 13.8% and was not changed by cAng-(1–7) treatment. MI increased heart weight and myocyte size, which was restored by cAng-(1–7) to sham levels. In addition, cAng-(1–7) lowered left ventricular end-diastolic pressure and improved endothelial function. The results suggest that cAng-(1–7) is a promising new agent in treatment of myocardial infarction and warrant further research. |
| format | Article |
| id | doaj-art-844ab8b1d4fe4269b705a5d6dac9631f |
| institution | Kabale University |
| issn | 2090-0384 2090-0392 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Hypertension |
| spelling | doaj-art-844ab8b1d4fe4269b705a5d6dac9631f2025-02-03T07:26:02ZengWileyInternational Journal of Hypertension2090-03842090-03922012-01-01201210.1155/2012/536426536426The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7) Analogue Cyclic Ang-(1–7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial InfarctionMatej Durik0Richard van Veghel1Anneke Kuipers2Rick Rink3Marijke Haas Jimoh Akanbi4Gert Moll5A. H. Jan Danser6Anton J. M. Roks7Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The NetherlandsDivision of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The NetherlandsLanthioPep, Nijenborgh 4, 9747 AG Groningen, The NetherlandsLanthioPep, Nijenborgh 4, 9747 AG Groningen, The NetherlandsBiOMaDe Technology Foundation, Groningen, The NetherlandsLanthioPep, Nijenborgh 4, 9747 AG Groningen, The NetherlandsDivision of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The NetherlandsDivision of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The NetherlandsModulation of renin-angiotensin system (RAS) by angiotensin-(1–7) (Ang-(1–7)) is an attractive approach to combat the detrimental consequences of myocardial infarction (MI). However Ang-(1–7) has limited clinical potential due to its unfavorable pharmacokinetic profile. We investigated effects of a stabilized, thioether-bridged analogue of Ang-(1–7) called cyclic Ang-(1–7) in rat model of myocardial infarction. Rats underwent coronary ligation or sham surgery. Two weeks thereafter infusion with 0.24 or 2.4 μg/kg/h cAng-(1–7) or saline was started for 8 weeks. Thereafter, cardiac morphometric and hemodynamic variables as wells as aortic endothelial function were measured. The average infarct size was 13.8% and was not changed by cAng-(1–7) treatment. MI increased heart weight and myocyte size, which was restored by cAng-(1–7) to sham levels. In addition, cAng-(1–7) lowered left ventricular end-diastolic pressure and improved endothelial function. The results suggest that cAng-(1–7) is a promising new agent in treatment of myocardial infarction and warrant further research.http://dx.doi.org/10.1155/2012/536426 |
| spellingShingle | Matej Durik Richard van Veghel Anneke Kuipers Rick Rink Marijke Haas Jimoh Akanbi Gert Moll A. H. Jan Danser Anton J. M. Roks The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7) Analogue Cyclic Ang-(1–7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction International Journal of Hypertension |
| title | The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7) Analogue Cyclic Ang-(1–7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction |
| title_full | The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7) Analogue Cyclic Ang-(1–7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction |
| title_fullStr | The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7) Analogue Cyclic Ang-(1–7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction |
| title_full_unstemmed | The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7) Analogue Cyclic Ang-(1–7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction |
| title_short | The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7) Analogue Cyclic Ang-(1–7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction |
| title_sort | effect of the thioether bridged stabilized angiotensin 1 7 analogue cyclic ang 1 7 on cardiac remodeling and endothelial function in rats with myocardial infarction |
| url | http://dx.doi.org/10.1155/2012/536426 |
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