Renin–Angiotensin System Antagonism Protects the Diabetic Heart from Ischemia/Reperfusion Injury in Variable Hyperglycemia Duration Settings by a Glucose Transporter Type 4-Mediated Pathway
Background: Diabetes mellitus (DM) is a risk factor for cardiovascular diseases, specifically, the ischemic heart diseases (IHD). The renin–angiotensin system (RAS) affects the heart directly and indirectly. However, its role in the protection of the heart against I/R injury is not completely unders...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/2/238 |
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| author | Aisha Al-Kouh Fawzi Babiker Maie Al-Bader |
| author_facet | Aisha Al-Kouh Fawzi Babiker Maie Al-Bader |
| author_sort | Aisha Al-Kouh |
| collection | DOAJ |
| description | Background: Diabetes mellitus (DM) is a risk factor for cardiovascular diseases, specifically, the ischemic heart diseases (IHD). The renin–angiotensin system (RAS) affects the heart directly and indirectly. However, its role in the protection of the heart against I/R injury is not completely understood. The aim of the current study was to evaluate the efficacy of the angiotensin-converting enzyme (ACE) inhibitor and Angiotensin II receptor (AT1R) blocker or a combination thereof in protection of the heart from I/R injury. Methods: Hearts isolated from adult male Wistar rats (<i>n</i> = 8) were subjected to high glucose levels; acute hyperglycemia or streptozotocin (STZ)-induced diabetes were used in this study. Hearts were subjected to I/R injury, treated with Captopril, an ACE inhibitor; Losartan, an AT1R antagonist; or a combination thereof. Hemodynamics data were measured using a suitable software for that purpose. Additionally, infarct size was evaluated using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. The levels of apoptosis markers (caspase-3 and -8), antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), nitric oxide synthase (eNOS), and glucose transporter type 4 (GLUT-4) protein levels were evaluated by Western blotting. Pro-inflammatory and anti-inflammatory cytokines levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Results: Captopril and Losartan alone or in combination abolished the effect of I/R injury in hearts subjected to acute hyperglycemia or STZ-induced diabetes. There was a significant (<i>p</i> < 0.05) recovery in hemodynamics, infarct size, and apoptosis markers following the treatment with Captopril, Losartan, or their combination. Treatment with Captopril, Losartan, or their combination significantly (<i>p</i> < 0.05) reduced pro-inflammatory cytokines and increased GLUT-4 protein levels. Conclusions: The blockade of the RAS system protected the diabetic heart from I/R injury. This protection followed a pathway that utilizes GLUT-4 to decrease the apoptosis markers, pro-inflammatory cytokines, and to increase the anti-inflammatory cytokines. This protection seems to employ a pathway which is not involving ERK1/2 and eNOS. |
| first_indexed | 2024-03-11T08:17:47Z |
| format | Article |
| id | doaj.art-45a8e0826c084aae975deb0115ba625c |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T08:17:47Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-45a8e0826c084aae975deb0115ba625c2023-11-16T22:36:54ZengMDPI AGPharmaceuticals1424-82472023-02-0116223810.3390/ph16020238Renin–Angiotensin System Antagonism Protects the Diabetic Heart from Ischemia/Reperfusion Injury in Variable Hyperglycemia Duration Settings by a Glucose Transporter Type 4-Mediated PathwayAisha Al-Kouh0Fawzi Babiker1Maie Al-Bader2Department of Physiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Kuwait City 13110, KuwaitDepartment of Physiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Kuwait City 13110, KuwaitDepartment of Physiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Kuwait City 13110, KuwaitBackground: Diabetes mellitus (DM) is a risk factor for cardiovascular diseases, specifically, the ischemic heart diseases (IHD). The renin–angiotensin system (RAS) affects the heart directly and indirectly. However, its role in the protection of the heart against I/R injury is not completely understood. The aim of the current study was to evaluate the efficacy of the angiotensin-converting enzyme (ACE) inhibitor and Angiotensin II receptor (AT1R) blocker or a combination thereof in protection of the heart from I/R injury. Methods: Hearts isolated from adult male Wistar rats (<i>n</i> = 8) were subjected to high glucose levels; acute hyperglycemia or streptozotocin (STZ)-induced diabetes were used in this study. Hearts were subjected to I/R injury, treated with Captopril, an ACE inhibitor; Losartan, an AT1R antagonist; or a combination thereof. Hemodynamics data were measured using a suitable software for that purpose. Additionally, infarct size was evaluated using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. The levels of apoptosis markers (caspase-3 and -8), antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), nitric oxide synthase (eNOS), and glucose transporter type 4 (GLUT-4) protein levels were evaluated by Western blotting. Pro-inflammatory and anti-inflammatory cytokines levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Results: Captopril and Losartan alone or in combination abolished the effect of I/R injury in hearts subjected to acute hyperglycemia or STZ-induced diabetes. There was a significant (<i>p</i> < 0.05) recovery in hemodynamics, infarct size, and apoptosis markers following the treatment with Captopril, Losartan, or their combination. Treatment with Captopril, Losartan, or their combination significantly (<i>p</i> < 0.05) reduced pro-inflammatory cytokines and increased GLUT-4 protein levels. Conclusions: The blockade of the RAS system protected the diabetic heart from I/R injury. This protection followed a pathway that utilizes GLUT-4 to decrease the apoptosis markers, pro-inflammatory cytokines, and to increase the anti-inflammatory cytokines. This protection seems to employ a pathway which is not involving ERK1/2 and eNOS.https://www.mdpi.com/1424-8247/16/2/238ischemia reperfusionRAScaptoprillosartandiabetes mellitushyperglycemia |
| spellingShingle | Aisha Al-Kouh Fawzi Babiker Maie Al-Bader Renin–Angiotensin System Antagonism Protects the Diabetic Heart from Ischemia/Reperfusion Injury in Variable Hyperglycemia Duration Settings by a Glucose Transporter Type 4-Mediated Pathway Pharmaceuticals ischemia reperfusion RAS captopril losartan diabetes mellitus hyperglycemia |
| title | Renin–Angiotensin System Antagonism Protects the Diabetic Heart from Ischemia/Reperfusion Injury in Variable Hyperglycemia Duration Settings by a Glucose Transporter Type 4-Mediated Pathway |
| title_full | Renin–Angiotensin System Antagonism Protects the Diabetic Heart from Ischemia/Reperfusion Injury in Variable Hyperglycemia Duration Settings by a Glucose Transporter Type 4-Mediated Pathway |
| title_fullStr | Renin–Angiotensin System Antagonism Protects the Diabetic Heart from Ischemia/Reperfusion Injury in Variable Hyperglycemia Duration Settings by a Glucose Transporter Type 4-Mediated Pathway |
| title_full_unstemmed | Renin–Angiotensin System Antagonism Protects the Diabetic Heart from Ischemia/Reperfusion Injury in Variable Hyperglycemia Duration Settings by a Glucose Transporter Type 4-Mediated Pathway |
| title_short | Renin–Angiotensin System Antagonism Protects the Diabetic Heart from Ischemia/Reperfusion Injury in Variable Hyperglycemia Duration Settings by a Glucose Transporter Type 4-Mediated Pathway |
| title_sort | renin angiotensin system antagonism protects the diabetic heart from ischemia reperfusion injury in variable hyperglycemia duration settings by a glucose transporter type 4 mediated pathway |
| topic | ischemia reperfusion RAS captopril losartan diabetes mellitus hyperglycemia |
| url | https://www.mdpi.com/1424-8247/16/2/238 |
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