Influence of the arachidonic acid cascade on the in vitro hepatic response to hypoxia.
Studies were undertaken to determine the effect of arachidonic acid, the precursor of bisenoic prostanoic acid derivatives, on the response of the isolated, perfused rabbit liver to hypoxia. Two and one half hours of severe hypoxia resulted in significant increases in hepatic vascular perfusion pressure, tissue wet weight, and the rates of cellular loss of lactic dehydrogenase, malic dehydrogenase, and acid phosphatase into the perfusing medium. Hypoxia also increased the rate of hepatic PGF2 alpha production by 25% after 2 1/2 hours (p less than 0.05, hypoxia vs sham). The addition of arachidonic acid (0.1 microgram/g/min for 150 minutes) to the perfusion medium of hypoxic livers significantly attenuated the changes in perfusion pressure, tissue wet weight, and loss of cellular enzymes. Arachidonic acid administration increased the rate of PGF2 alpha production by 100% (p less than 0.05, sham vs hypoxia + arachidonic acid) within 30 min after hypoxia and maintained this rate for the duration of the study. These results demonstrate that hypoxia mediated prostaglandin F2 alpha synthesis in the rabbit liver can occur in the absence of neural and blood borne components and that significant activation of the arachidonic acid cascade via the administration of exogenous arachidonic acid has a salutary effect on hepatic hemodynamics and cellular integrity during hypoxia.
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion / Q000295:instrumentation; D011312:Pressure; D011460:Prostaglandins F / Q000096:biosynthesis*; D011817:Rabbits; D013997:Time Factors
D001095:Arachidonic Acids; D011460:Prostaglandins F; D007770:L-Lactate Dehydrogenase; D008291:Malate Dehydrogenase; D000135:Acid Phosphatase