Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic rats
Hypothesis: This study was designed to investigate the cardio-renal protective effect of AVE-0991, a non-peptide Mas-receptor agonist, and A-779, a Mas-receptor antagonist, in diabetic rats. Materials and methods: Wistar rats treated with streptozotocin (50 mg/kg, i.p., once), developed diabetes mel...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2012-09-01
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| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.1177/1470320311435534 |
| _version_ | 1797284180525056000 |
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| author | Kulwinder Singh Kuldeepak Sharma Manjeet Singh PL Sharma |
| author_facet | Kulwinder Singh Kuldeepak Sharma Manjeet Singh PL Sharma |
| author_sort | Kulwinder Singh |
| collection | DOAJ |
| description | Hypothesis: This study was designed to investigate the cardio-renal protective effect of AVE-0991, a non-peptide Mas-receptor agonist, and A-779, a Mas-receptor antagonist, in diabetic rats. Materials and methods: Wistar rats treated with streptozotocin (50 mg/kg, i.p., once), developed diabetes mellitus after 1 week. After 8 weeks, myocardial functions were assessed by measuring left ventricular developed pressure (LVDP), rate of left ventricular pressure development (d p /d t max ), rate of left ventricular pressure decay (d p /d t min ) and left ventricular end diastolic pressure (LVEDP) on an isolated Langendorff’s heart preparation. Further, mean arterial blood pressure (MABP) was measured by using the tail-cuff method. Assessment of renal functions and lipid profile was carried out using a spectrophotometer. Results: The administration of streptozotocin to rats produced persistent hyperglycaemia, dyslipidaemia and hypertension which consequently produced cardiac and renal dysfunction in 8 weeks. AVE0991 treatment produced cardio-renal protective effects, as evidenced by a significant increase in LVDP, d p /d t max , d p /d t min and a significant decrease in LVEDP, BUN, and protein urea. Further, AVE-0991 treatment for the first time has been shown to reduce dyslipidaemia and produced antihyperglycaemic activity in streptozotocin-treated rats. However, MABP and creatinine clearance remained unaffected with AVE-0991 treatment. Conclusions: AVE-0991 produced cardio-renal protection possibly by improving glucose and lipid metabolism in diabetic rats, independent of its blood pressure lowering action. |
| first_indexed | 2024-03-07T17:44:16Z |
| format | Article |
| id | doaj.art-d6199b71e71f4a9fb60a6ba441481648 |
| institution | Directory Open Access Journal |
| issn | 1470-3203 1752-8976 |
| language | English |
| last_indexed | 2024-03-07T17:44:16Z |
| publishDate | 2012-09-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-d6199b71e71f4a9fb60a6ba4414816482024-03-02T15:25:10ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32031752-89762012-09-011310.1177/1470320311435534Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic ratsKulwinder SinghKuldeepak SharmaManjeet SinghPL SharmaHypothesis: This study was designed to investigate the cardio-renal protective effect of AVE-0991, a non-peptide Mas-receptor agonist, and A-779, a Mas-receptor antagonist, in diabetic rats. Materials and methods: Wistar rats treated with streptozotocin (50 mg/kg, i.p., once), developed diabetes mellitus after 1 week. After 8 weeks, myocardial functions were assessed by measuring left ventricular developed pressure (LVDP), rate of left ventricular pressure development (d p /d t max ), rate of left ventricular pressure decay (d p /d t min ) and left ventricular end diastolic pressure (LVEDP) on an isolated Langendorff’s heart preparation. Further, mean arterial blood pressure (MABP) was measured by using the tail-cuff method. Assessment of renal functions and lipid profile was carried out using a spectrophotometer. Results: The administration of streptozotocin to rats produced persistent hyperglycaemia, dyslipidaemia and hypertension which consequently produced cardiac and renal dysfunction in 8 weeks. AVE0991 treatment produced cardio-renal protective effects, as evidenced by a significant increase in LVDP, d p /d t max , d p /d t min and a significant decrease in LVEDP, BUN, and protein urea. Further, AVE-0991 treatment for the first time has been shown to reduce dyslipidaemia and produced antihyperglycaemic activity in streptozotocin-treated rats. However, MABP and creatinine clearance remained unaffected with AVE-0991 treatment. Conclusions: AVE-0991 produced cardio-renal protection possibly by improving glucose and lipid metabolism in diabetic rats, independent of its blood pressure lowering action.https://doi.org/10.1177/1470320311435534 |
| spellingShingle | Kulwinder Singh Kuldeepak Sharma Manjeet Singh PL Sharma Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic rats Journal of the Renin-Angiotensin-Aldosterone System |
| title | Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic rats |
| title_full | Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic rats |
| title_fullStr | Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic rats |
| title_full_unstemmed | Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic rats |
| title_short | Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic rats |
| title_sort | possible mechanism of the cardio renal protective effects of ave 0991 a non peptide mas receptor agonist in diabetic rats |
| url | https://doi.org/10.1177/1470320311435534 |
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