The action of oxybutynin on haemodynamics and metabolism in the perfused rat liver.
The present study was planned to investigate the possible action of oxybutynin on liver haemodynamics and its influence on metabolic variables. The isolated liver perfused either bivascularly or monovascularly in the non-recirculating system was used for the experiments and Krebs/Henseleit-bicarbonate buffer (pH 7.4) as a perfusion fluid. Oxybutynin (25-200 microM) was infused, the infusion time for each concentration being 14 min. Portally infused oxybutynin increased the perfusion pressure starting at 100 microM. Oxygen uptake was diminished, also starting at 100 microM. Arterially infused oxybutynin also increased the perfusion pressure in the hepatic artery. Lactate and pyruvate releases were considerably diminished by oxybutynin. Glucose release showed a small initial stimulation, then returned to values slightly below the basal ones. Cessation of oxybutynin infusion resulted in progressive stimulation of glucose release. When Ca2+ was omitted all effects of oxybutynin vanished. The hepatic contents of glucose, glucose 6-phosphate and lactate in the presence of 200 microM oxybutynin increased 7.8-, 4.6- and 5.1 times, respectively. The pyruvate content was not changed. The ATP content was diminished by 26.6% in the presence of 200 microM oxybutynin, but the AMP content was increased by 64.3%. The ADP content was not changed. Apparently, upon administration of oxybutynin, a considerable fraction of the liver parenchyma ceased to be irrigated or almost so, which is apparent from the concomitant inhibition of oxygen uptake, pressure increase and inhibition of glucose, lactate and pyruvate release together with the simultaneous intracellular accumulation of glucose, lactate and glucose 6-phosphate.
Comar
Jurandir Fernando
JF
Laboratory of Liver Metabolism, University of Maringá, Maringá, Brazil.
Suzuki-Kemmelmeier
Fumie
F
Bracht
Adelar
A
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000378:metabolism*; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000227:Adenine Nucleotides; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D019344:Lactic Acid; D019298:Glucose-6-Phosphate; D019289:Pyruvic Acid; D005947:Glucose; C005419:oxybutynin; D002118:Calcium