Role of acidosis in regulating hepatic nitrogen metabolism during fasting in conscious dog.
This study was designed to investigate the role that acidosis plays in the metabolic responses to fasting. Eighteen conscious dogs with surgically implanted catheters in the femoral artery and in the hepatic, portal, and renal veins were studied. Six were fasted for 24 h and 12 were fasted for 4 days (96 h). On the day of the study, six 4-day fasted dogs were infused intravenously with NaHCO3 (10 mumol X kg-1 X min-1) for 3 h, while the rest received saline and acted as controls. Splanchnic balances of glutamine, alanine, blood urea nitrogen, ammonia, lactate, beta-hydroxybutyrate, and acetoacetate were estimated using the Fick principle. Blood flow to the splanchnic and renal beds were estimated using indocyanine green and p-aminohippurate extraction methods, respectively. The infusion of NaHCO3 nearly abolished the base deficit associated with fasting and normalized arterial bicarbonate levels but did not alter blood pH. It suppressed but did not abolish hepatic glutamine output by 60%. This was associated with a shift in cytoplasmic and mitochondrial redox potentials of the hepatocyte as evident by a decrease in hepatic production of beta-hydroxybutyrate and an increase in hepatic production of acetoacetate and a decrease in hepatic lactate utilization. Concomitantly, renal glutamine uptake decreased. Glutamine release of skeletal muscle was unchanged. The data suggest that hepatic glutamine synthesis and release seen with 4-day fasting has two components: a bicarbonate-dependent component that is influenced by the redox potential of the hepatocyte and a bicarbonate-independent component, the nature of which is not yet clear.(ABSTRACT TRUNCATED AT 250 WORDS)
D000138:Acidosis / Q000378:metabolism*; D000409:Alanine / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D005215:Fasting; D005260:Female; D005934:Glucagon / Q000097:blood; D005971:Glutamates / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D009584:Nitrogen / Q000378:metabolism*; D011188:Potassium / Q000097:blood
D001639:Bicarbonates; D001786:Blood Glucose; D002395:Catecholamines; D005971:Glutamates; D007328:Insulin; D007773:Lactates; D005973:Glutamine; D000641:Ammonia; D005934:Glucagon; D009584:Nitrogen; D000409:Alanine; D011188:Potassium; D006854:Hydrocortisone