Chronic Treatment with Ang-(1-7) Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes
Angiotensin-(1-7) [Ang-(1-7)] may have beneficial effects in diabetes mellitus-induced erectile dysfunction (DMIED) but its molecular actions in the diabetic corpus cavernosum (CC) are not known. We characterized the effects of diabetes and/or chronic in vivo administration of Ang-(1-7) on vascular...
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Wiley
2014-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2014/142154 |
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| author | Mariam H. M. Yousif Batoul Makki Ahmed Z. El-Hashim Saghir Akhtar Ibrahim F. Benter |
| author_facet | Mariam H. M. Yousif Batoul Makki Ahmed Z. El-Hashim Saghir Akhtar Ibrahim F. Benter |
| author_sort | Mariam H. M. Yousif |
| collection | DOAJ |
| description | Angiotensin-(1-7) [Ang-(1-7)] may have beneficial effects in diabetes mellitus-induced erectile dysfunction (DMIED) but its molecular actions in the diabetic corpus cavernosum (CC) are not known. We characterized the effects of diabetes and/or chronic in vivo administration of Ang-(1-7) on vascular reactivity in the rat corpus cavernosum (CC) and on protein expression levels of potential downstream effectors of the renin-angiotensin-aldosterone system (RAAS) such as angiotensin-converting enzyme (ACE), ACE2, Rho kinases 1 and 2 (ROCK1 and ROCK2), and omega-hydroxylase, the cytochrome-P450 enzyme that metabolizes arachidonic acid to form the vasoconstrictor, 20-hydroxyeicosatetraenoic acid. Streptozotocin-treated rats were chronicically administered Ang-(1-7) with or without A779, a Mas receptor antagonist, during weeks 4 to 6 of diabetes. Ang-(1-7) reversed diabetes-induced abnormal reactivity to vasoactive agents (endothelin-1, phenylepherine, and carbachol) in the CC without correcting hyperglycemia. Six weeks of diabetes led to elevated ACE, ROCK1, ROCK 2, and omega-hydroxylase and a concomitant decrease in ACE2 protein expression levels that were normalized by Ang-(1-7) treatment but not upon coadministration of A779. These data are supportive of the notion that the beneficial effects of Ang-(1-7) in DMIED involve counterregulation of diabetes-induced changes in ACE, ACE2, Rho kinases, and omega-hydroxylase proteins in the diabetic CC via a Mas receptor-dependent mechanism. |
| format | Article |
| id | doaj-art-013eab296e8f48acba85fcb42839e79f |
| institution | OA Journals |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-013eab296e8f48acba85fcb42839e79f2025-08-20T02:01:34ZengWileyJournal of Diabetes Research2314-67452314-67532014-01-01201410.1155/2014/142154142154Chronic Treatment with Ang-(1-7) Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 DiabetesMariam H. M. Yousif0Batoul Makki1Ahmed Z. El-Hashim2Saghir Akhtar3Ibrahim F. Benter4Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, P.O. Box 24923, 13110 Safat, KuwaitDepartment of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, P.O. Box 24923, 13110 Safat, KuwaitDepartment of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, 13110 Safat, KuwaitDepartment of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, P.O. Box 24923, 13110 Safat, KuwaitDepartment of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, P.O. Box 24923, 13110 Safat, KuwaitAngiotensin-(1-7) [Ang-(1-7)] may have beneficial effects in diabetes mellitus-induced erectile dysfunction (DMIED) but its molecular actions in the diabetic corpus cavernosum (CC) are not known. We characterized the effects of diabetes and/or chronic in vivo administration of Ang-(1-7) on vascular reactivity in the rat corpus cavernosum (CC) and on protein expression levels of potential downstream effectors of the renin-angiotensin-aldosterone system (RAAS) such as angiotensin-converting enzyme (ACE), ACE2, Rho kinases 1 and 2 (ROCK1 and ROCK2), and omega-hydroxylase, the cytochrome-P450 enzyme that metabolizes arachidonic acid to form the vasoconstrictor, 20-hydroxyeicosatetraenoic acid. Streptozotocin-treated rats were chronicically administered Ang-(1-7) with or without A779, a Mas receptor antagonist, during weeks 4 to 6 of diabetes. Ang-(1-7) reversed diabetes-induced abnormal reactivity to vasoactive agents (endothelin-1, phenylepherine, and carbachol) in the CC without correcting hyperglycemia. Six weeks of diabetes led to elevated ACE, ROCK1, ROCK 2, and omega-hydroxylase and a concomitant decrease in ACE2 protein expression levels that were normalized by Ang-(1-7) treatment but not upon coadministration of A779. These data are supportive of the notion that the beneficial effects of Ang-(1-7) in DMIED involve counterregulation of diabetes-induced changes in ACE, ACE2, Rho kinases, and omega-hydroxylase proteins in the diabetic CC via a Mas receptor-dependent mechanism.http://dx.doi.org/10.1155/2014/142154 |
| spellingShingle | Mariam H. M. Yousif Batoul Makki Ahmed Z. El-Hashim Saghir Akhtar Ibrahim F. Benter Chronic Treatment with Ang-(1-7) Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes Journal of Diabetes Research |
| title | Chronic Treatment with Ang-(1-7) Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes |
| title_full | Chronic Treatment with Ang-(1-7) Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes |
| title_fullStr | Chronic Treatment with Ang-(1-7) Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes |
| title_full_unstemmed | Chronic Treatment with Ang-(1-7) Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes |
| title_short | Chronic Treatment with Ang-(1-7) Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes |
| title_sort | chronic treatment with ang 1 7 reverses abnormal reactivity in the corpus cavernosum and normalizes diabetes induced changes in the protein levels of ace ace2 rock1 rock2 and omega hydroxylase in a rat model of type 1 diabetes |
| url | http://dx.doi.org/10.1155/2014/142154 |
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