Investigating the role of endogenous opioids and KATP channels in glycerol-induced acute renal failure

• Published in: Fundamental & clinical pharmacology 2012-06, Vol.26 (3), p.347-355
• Main Authors: Sauriyal, Dharmraj Singh, Jaggi, Amteshwar Singh, Singh, Nirmal, Muthuraman, Arunachalam
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - metabolism; acute renal failure; Animals; Biological and medical sciences; Blood Urea Nitrogen; endogenous opioids; Female; Glyburide - pharmacology; glycerol; Glycerol - toxicity; KATP channels; Male; Medical sciences; Naltrexone - pharmacology; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Opioid Peptides - antagonists & inhibitors; Opioid Peptides - metabolism; Opioid Peptides - physiology; Pharmacology. Drug treatments; Potassium Channels - physiology; Rats; Rats, Wistar; Renal failure; rhabdomyolysis
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/j.1472-8206.2011.00936.x

The present study was designed to investigate the possible role of endogenous opioids and KATP channels in glycerol‐induced acute renal failure (ARF) in rats. The rats were subjected to rhabdomyolytic ARF by single intramuscular injection of hypertonic glycerol (50% v/v; 8 mL/kg), and the animals were sacrificed after 24 h of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury. Naltrexone (2.5, 5.0 and 10.0 mg/kg s.c.), glibenclamide (5.0 and 10.0 mg/kg i.p.), and minoxidil (25 and 50 mg/kg) were employed to explore the role of endogenous opioids and KATP channels in rhabdomyolysis‐induced ARF. Pretreatment with naltrexone and glibenclamide attenuated hypertonic glycerol‐induced renal dysfunction in a dose‐dependent manner, suggesting the role of endogenous opioids and KATP channels in the pathogenesis of myoglobuniric renal failure. However, the simultaneous pretreatment with naltrexone (10 mg/kg s.c.) and glibenclamide (10 mg/kg i.p.) did not enhance the reno‐protective effects of individual drugs, suggesting that release of endogenous opioids and opening of KATP channels constitute a single pathway in acute renal injury triggered by hypertonic glycerol‐induced rhabdomyolysis. Furthermore, administration of minoxidil abolished the attenuating effects of naltrexone in glycerol‐induced renal failure, suggesting that opening of KATP channels is downstream to opioid receptor activation. It is concluded that hypertonic glycerol‐induced rhabdomyolysis may involve release of endogenous opioids that in turn modulate KATP channels to contribute in the pathogenesis of ARF.