title: Protective effect of losartan and ramipril against stress induced insulin resistance and related complications: Anti-inflammatory mechanisms.
abstract: Chronic restraint stress (CRS) is known to cause various behavioural and biochemical alterations, leading to several negative health outcomes. The present study was designed to explore the impact of inhibiting Renin angiotensin aldosterone system (RAAS) and inflammatory pathways in stress pathophysiology. In the present study, male LACA mice were subjected to restraint stress daily for 30 days. Losartan, nimesulide, ramipril, minocycline and their combinations were administered 45min prior to restraint stress daily and their effects were observed. Restraint stressed mice depicted depression like behavior along with increased oxidative stress markers in their brains. CRS induced insulin resistance depicted by hyperglycemia, hyperinsulinemia, hypercholesteremia, increased glycosylated hemoglobin and HOMA-IR. Besides, treatment with losartan, nimesulide, ramipril and minocycline significantly restored the behavioural and biochemical alterations and improved insulin sensitivity in stressed mice. Combination treatments synergistically reversed depression like behavior and decreased plasma glucose levels. Moreover they restored insulin levels, glycosylated hemoglobin levels and HOMA-IR values to the normal. This study signifies the synergistic effect of simultaneously blocking RAS and inflammatory pathways in stress pathophysiology.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Barinder
authors.initials: B
authors.lastname: Singh
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Mourya
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India. Electronic address: spilkhwal@rediffmail.com.
authors.forename: Sangeeta Pilkhwal
authors.initials: SP
authors.lastname: Sah
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D007333:Insulin Resistance; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D017257:Ramipril / Q000494:pharmacology* / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D019808:Losartan; D017257:Ramipril
keywords: Chronic restraint stress; HPA axis; Inflammation; Insulin resistance; Renin angiotensin aldosterone system