Alterations in splanchnic cyclic nucleotide levels in splanchnic artery occlusion shock and their modification by dexamethasone.
The effects of dexamethasone sodium phosphate (DSP), 5 mg/kg, administration on the biochemical alterations in hepatic tissue subsequent to the production os splanchnic artery occlusion (SAO) shock was investigated. Following the induction of SAO shock, DSP-treated dogs exhibited a significantly improved cardiovascular status compared to placebo-treated shocked dogs, 2 hr after release of the occlusion, biopsies of the liver were taken and analyzed for beta-glucuronidase (BG), adenosine-3',5'-cyclic monophosphate (cAMP) and guanosine-3',5'-cyclic monophosphate (cGMP) content. SAO shock produced a significant increase in hepatic free BG activity which was reversed by DSP pretreatment. Additionally, SAO shock decreased hepatic cAMP levels, increased cGMP levels and significantly lowered the hepatic ratio of cAMP/cGMP. These changes in cyclic nucleotide levels were reversed by DSP administration and were found to be inversely related to changes in hepatic free BG activity. Thus, the ratio of cellular cAMP/cGMP may function as a regulatory mechanism for lysosomal enzyme release secondary to ischemia and hypoxia. Further, DSP may act to maintain lysosomal integrity in ischemic tissues by preservation of cAMP/cGMP ratios.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects; D008297:Male; D012769:Shock / Q000378:metabolism*; D013997:Time Factors
D003907:Dexamethasone; D000242:Cyclic AMP; D005966:Glucuronidase; D006152:Cyclic GMP