title: Effective blockade of RAAS by combination of aliskiren and olmesartan improves glucose homeostasis, glomerular filtration rate along with renal variables in streptozotocin induced diabetic rats.
abstract: The present study aims to investigate the combined and individual treatment of aliskiren and olmesartan for 8 weeks in streptozotocin induced diabetic rats provide an effective blockade of RAAS by improving glucose homeostasis, glomerular filtration rate along with renal variables thereby delaying the progression of the disease. Streptozotocin induced diabetic rats were administered with aliskiren (10mg/kg/day), olmesartan (6mg/kg/day) alone and in combination. To identify the glucose homeostasis, translocation of glucose transporter proteins in liver and muscle was observed by their expression after treatment. Glomerular filtration rate is estimated using serum creatinine, cystatin C and beta 2 microglobulin. This study also examined the effects of combination and monotherapy on various renal variables viz. albumin, total proteins, TGF-β, TNF-α, VEGF, nitric oxide, adiponectin and erythropoeitin. In addition, histopathological and anti-apoptotic profile of kidney was also investigated. The present study indicates that dual blockade of RAAS improved glucose homeostasis and confirms the nephroprotective effects of the combined treatment of aliskiren and olmesartan independent of their antihypertensive property in the STZ induced diabetes. In addition, its antifibrotic, antiproteinuric effects indicate that combination treatment might be potential as an important therapeutic option for chronic fibrotic diseases in renal complications.
authors.affiliation: Delhi Institute of Pharmaceutical Sciences and Research, Pushp Vihar, Sector-3, MB Road, New Delhi 110 017, India. Sonia.gandhi@rediffmail.com
authors.forename: Sonia
authors.initials: S
authors.lastname: Gandhi
authors.forename: B P
authors.initials: BP
authors.lastname: Srinivasan
authors.forename: Atul Sureshrao
authors.initials: AS
authors.lastname: Akarte
mesh_terms: D000577:Amides / Q000008:administration & dosage* / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005650:Fumarates / Q000008:administration & dosage* / Q000627:therapeutic use; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D051273:Glucose Transporter Type 2 / Q000032:analysis; D051275:Glucose Transporter Type 4 / Q000032:analysis; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008099:Liver / Q000737:chemistry; D018482:Muscle, Skeletal / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012709:Serum Albumin / Q000032:analysis; D013777:Tetrazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001786:Blood Glucose; D005650:Fumarates; D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D007093:Imidazoles; D007328:Insulin; D012709:Serum Albumin; C495683:Slc2a2 protein, rat; C495694:Slc2a4 protein, rat; D013777:Tetrazoles; C446481:aliskiren; C437965:olmesartan