title: Caffeine-induced natriuresis and diuresis via blockade of hepatic adenosine-mediated sensory nerves and a hepatorenal reflex.
abstract: The hepatorenal reflex, activated by intrahepatic adenosine, is involved in the regulation of urine production in healthy rats and renal pathogenesis secondary to liver injury. Hepatic adenosine A1 receptors regulate the hepatorenal reflex. The aim of the present study was to evaluate whether caffeine mediates renal natriuresis and diuresis in healthy and diseased liver through this mechanism. Rats were anesthetized and instrumented to monitor systemic, hepatic, and renal circulation and urine production. Intrahepatic (intraportal but not intravenous) caffeine (5 mg·kg-1) increased urine flow (~82%) in healthy rats. This effect was abolished by liver denervation. Intraportal infusion of adenosine decreased urine production, and this response was abolished by intraportal but not intravenous caffeine. Liver injury was induced by intraperitoneal injection of thioacetamide (500 mg·kg-1), and functional assessment was performed 24 h later. Liver injury was associated with lower (~30%) glomerular filtration rate, lower (~18%) renal arterial blood flow, and lower urine production. Intraportal but not intravenous caffeine improved basal urine production and renal ability to increase urine production in response to saline overload. The liver-dependent diuretic effect of caffeine is consistent with the hypothesis for the adenosine-mediated mechanism of hepatorenal syndrome.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, A210-753 McDermot Avenue, Winnipeg, MB R3E 0W3, Canada.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ming
authors.forename: W Wayne
authors.initials: WW
authors.lastname: Lautt
mesh_terms: D000241:Adenosine / Q000037:antagonists & inhibitors; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects*; D007668:Kidney / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D002110:Caffeine; D000241:Adenosine