Synergistic Effects of Dantrolene and Nimodipine on the Phenylephrine-Induced Contraction and ACh-Induced Relaxation in Aortic Rings from Diabetic Rats
Diabetics have a higher risk of developing cerebral vasospasms (CVSP) than nondiabetics. The addition of the ryanodine receptor (RyR) blocker dantrolene to standard therapies reduces vasospasms in nondiabetics. Whether diabetics with CVSP also benefit from this drug, however, is unknown. We evaluate...
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Wiley
2018-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2018/9790303 |
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| author | Maria J. Crespo Marie Roman Jonathan Matias Myrna Morales Hector Torres Jose Quidgley |
| author_facet | Maria J. Crespo Marie Roman Jonathan Matias Myrna Morales Hector Torres Jose Quidgley |
| author_sort | Maria J. Crespo |
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| description | Diabetics have a higher risk of developing cerebral vasospasms (CVSP) than nondiabetics. The addition of the ryanodine receptor (RyR) blocker dantrolene to standard therapies reduces vasospasms in nondiabetics. Whether diabetics with CVSP also benefit from this drug, however, is unknown. We evaluated the effects of a 30 min incubation with dantrolene (50 μM), nimodipine (50 nM), and both drugs in combination, on phenylephrine- (PHE-) induced contraction and on acetylcholine- (ACh-) induced relaxation in aortic rings from streptozotocin (STZ) diabetic rats. Age-matched, nondiabetic rats served as controls. The oxidative stress markers malondialdehyde (MDA) and 4-hydroxyalkenal (4-HAE) were also evaluated in the presence and absence of dantrolene and nimodipine. The combination of these two drugs acted synergistically to reduce the PHE-induced contraction by 80% in both diabetics and controls. In contrast, it increased the Emax value for ACh-induced relaxation (from 56.46 ± 5.14% to 96.21 ± 7.50%; n=6, P<0.05), and it decreased MDA + 4-HAE values in diabetic rats only. These results suggest that the combination of dantrolene and nimodipine benefits both diabetics and nondiabetics by decreasing arterial tone synergistically. |
| format | Article |
| id | doaj-art-9b404f8c3e3b4f17b20d707b6ab2fa61 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
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| series | International Journal of Endocrinology |
| spelling | doaj-art-9b404f8c3e3b4f17b20d707b6ab2fa612025-02-03T01:09:26ZengWileyInternational Journal of Endocrinology1687-83371687-83452018-01-01201810.1155/2018/97903039790303Synergistic Effects of Dantrolene and Nimodipine on the Phenylephrine-Induced Contraction and ACh-Induced Relaxation in Aortic Rings from Diabetic RatsMaria J. Crespo0Marie Roman1Jonathan Matias2Myrna Morales3Hector Torres4Jose Quidgley5Department of Physiology, University of Puerto Rico-School of Medicine, San Juan, PR, USADepartment of Physiology, University of Puerto Rico-School of Medicine, San Juan, PR, USADepartment of Anesthesiology, University of Puerto Rico-School of Medicine, San Juan, PR, USADepartment of Anesthesiology, University of Puerto Rico-School of Medicine, San Juan, PR, USADepartment of Anesthesiology, University of Puerto Rico-School of Medicine, San Juan, PR, USADepartment of Physiology, University of Puerto Rico-School of Medicine, San Juan, PR, USADiabetics have a higher risk of developing cerebral vasospasms (CVSP) than nondiabetics. The addition of the ryanodine receptor (RyR) blocker dantrolene to standard therapies reduces vasospasms in nondiabetics. Whether diabetics with CVSP also benefit from this drug, however, is unknown. We evaluated the effects of a 30 min incubation with dantrolene (50 μM), nimodipine (50 nM), and both drugs in combination, on phenylephrine- (PHE-) induced contraction and on acetylcholine- (ACh-) induced relaxation in aortic rings from streptozotocin (STZ) diabetic rats. Age-matched, nondiabetic rats served as controls. The oxidative stress markers malondialdehyde (MDA) and 4-hydroxyalkenal (4-HAE) were also evaluated in the presence and absence of dantrolene and nimodipine. The combination of these two drugs acted synergistically to reduce the PHE-induced contraction by 80% in both diabetics and controls. In contrast, it increased the Emax value for ACh-induced relaxation (from 56.46 ± 5.14% to 96.21 ± 7.50%; n=6, P<0.05), and it decreased MDA + 4-HAE values in diabetic rats only. These results suggest that the combination of dantrolene and nimodipine benefits both diabetics and nondiabetics by decreasing arterial tone synergistically.http://dx.doi.org/10.1155/2018/9790303 |
| spellingShingle | Maria J. Crespo Marie Roman Jonathan Matias Myrna Morales Hector Torres Jose Quidgley Synergistic Effects of Dantrolene and Nimodipine on the Phenylephrine-Induced Contraction and ACh-Induced Relaxation in Aortic Rings from Diabetic Rats International Journal of Endocrinology |
| title | Synergistic Effects of Dantrolene and Nimodipine on the Phenylephrine-Induced Contraction and ACh-Induced Relaxation in Aortic Rings from Diabetic Rats |
| title_full | Synergistic Effects of Dantrolene and Nimodipine on the Phenylephrine-Induced Contraction and ACh-Induced Relaxation in Aortic Rings from Diabetic Rats |
| title_fullStr | Synergistic Effects of Dantrolene and Nimodipine on the Phenylephrine-Induced Contraction and ACh-Induced Relaxation in Aortic Rings from Diabetic Rats |
| title_full_unstemmed | Synergistic Effects of Dantrolene and Nimodipine on the Phenylephrine-Induced Contraction and ACh-Induced Relaxation in Aortic Rings from Diabetic Rats |
| title_short | Synergistic Effects of Dantrolene and Nimodipine on the Phenylephrine-Induced Contraction and ACh-Induced Relaxation in Aortic Rings from Diabetic Rats |
| title_sort | synergistic effects of dantrolene and nimodipine on the phenylephrine induced contraction and ach induced relaxation in aortic rings from diabetic rats |
| url | http://dx.doi.org/10.1155/2018/9790303 |
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