Relationship between oxidative hepatic metabolism, urinary sodium excretion and sympathetic nerve activity in experimental cirrhosis in the rat.
This study investigated the relationship between changes in renal sympathetic activity as assessed by renal norepinephrine spill-over and the onset of renal sodium retention in the phenobarbital/carbon tetrachloride model of experimental cirrhosis in rats. In this model, sodium retention occurs when hepatic function, assessed by the aminopyrine breath test (ABT), falls below a critical threshold. Three groups of rats, studied on a constant salt diet, included a group with cirrhosis and sodium retention, a group with cirrhosis of similar duration and no sodium retention and a time-control phenobarbitaltreated group. ABT, renal plasma flow (RPF), glomerular filtration rate (GFR) and mean arterial pressure (MAP) were measured at the time of catecholamine sampling in anesthetized rats. Cirrhosis was associated with reductions in MAP, no change in RPF and GFR, and an ABT below the threshold in rats with sodium retention. In contrast, rats without sodium retention had liver function above the threshold. Renal norepinephrine spill-over increased continuously from controls to non-sodium retaining and sodium retaining animals. The difference between sodium retaining animals and controls was significant. Norepinephrine spill-over correlated to ABT and MAP but not urinary salt excretion. The data suggest that, under these experimental conditions, increased sympathetic activity may contribute to the onset of sodium retention. A plausible explanation for the continuous increase is that catecholamines are released as a compensatory mechanism in response to a primary yet undefined vasodilator.
Wensing
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Center for Clinical Pharmacology, University of Pittsburgh Medical Center, PA.
Sabra
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Branch
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D000632:Aminopyrine / Q000493:pharmacokinetics*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001944:Breath Tests; D002251:Carbon Tetrachloride; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000503:physiopathology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood; D010084:Oxidation-Reduction; D010634:Phenobarbital; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
D000632:Aminopyrine; D002251:Carbon Tetrachloride; D009638:Norepinephrine; D010634:Phenobarbital