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 (dp/dt (max)), rate of left ventricular pressure decay (dp/dt (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, dp/dt (max), dp/dt (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.
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 diabeticrats. 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 (dp/dt (max)), rate of left ventricular pressure decay (dp/dt (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, dp/dt (max), dp/dt (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 diabeticrats, independent of its blood pressure lowering action.
Authors: Anna Gromotowicz-Poplawska; Piotr Szoka; Patrycjusz Kolodziejczyk; Karol Kramkowski; Marzena Wojewodzka-Zelezniakowicz; Ewa Chabielska Journal: Exp Biol Med (Maywood) Date: 2016-07-19
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Authors: Larissa B Teixeira; Lucas T Parreiras-E-Silva; Thiago Bruder-Nascimento; Diego A Duarte; Sarah C Simões; Rafael M Costa; Deisy Y Rodríguez; Pedro A B Ferreira; Carlos A A Silva; Emiliana P Abrao; Eduardo B Oliveira; Michel Bouvier; Rita C Tostes; Claudio M Costa-Neto Journal: Sci Rep Date: 2017-09-19 Impact factor: 4.379
Authors: Sabine Klein; Chandana B Herath; Robert Schierwagen; Josephine Grace; Tom Haltenhof; Frank E Uschner; Christian P Strassburg; Tilman Sauerbruch; Thomas Walther; Peter W Angus; Jonel Trebicka Journal: PLoS One Date: 2015-09-25 Impact factor: 3.240