Blockade of cannabinoid CB1 receptors improves renal function, metabolic profile, and increased survival of obese Zucker rats
| Autor: | Jean-Marc Herbert, Philip Janiak, J.-P. Bidouard, G. Le Fur, J P Maffrand, Bruno Poirier, I. Barbosa, L. Gouraud, S. E. O'Connor, C. Cadrouvele, J. Dedio, F. Pierre |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
Nephrology renal failure medicine.medical_specialty Renal Hypertrophy Renal function Type 2 diabetes Kidney Eating longevity Piperidines Receptor Cannabinoid CB1 Rimonabant Internal medicine Animals Medicine Obesity endocannabinoids type II diabetes business.industry Body Weight metabolic risk factors medicine.disease Lipids Survival Analysis Angiotensin II Rats Rats Zucker Disease Models Animal Endocrinology Renal physiology Kidney Failure Chronic Pyrazoles Adiponectin business medicine.drug Kidney disease |
| Zdroj: | Kidney International. 72(11):1345-1357 |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/sj.ki.5002540 |
| Popis: | Obesity is a major risk factor in the development of chronic renal failure. Rimonabant, a cannabinoid CB1 receptor antagonist, improves body weight and metabolic disorders; however, its effect on mortality and chronic renal failure associated with obesity is unknown. Obese Zucker rats received either rimonabant or vehicle for 12 months and were compared to a pair-fed but untreated group of obese rats. Mortality in the obese rats was significantly reduced by rimonabant along with a sustained decrease in body weight, transient reduction in food intake, and an increase in plasma adiponectin. This was associated with significant reduction in plasma total cholesterol, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, triglycerides, glucose, norepinephrine, plasminogen activator inhibitor 1, and preservation of pancreatic weight and β -cell mass index. The cannabinoid antagonist attenuated the increase in proteinuria, urinary N -acetylglucosaminidase excretion, plasma creatinine, and urea nitrogen levels while improving creatinine clearance. Renal hypertrophy along with glomerular and tubulointerstitial lesions were reduced by rimonabant. Although the drug did not modify hemodynamics, it normalized the pressor response to angiotensin II. Our study suggests that in a rat model of chronic renal failure due to obesity, rimonabant preserves renal function and increases survival. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|