The effects of soman on norepinephrine uptake, release, and metabolism.
The effects of 7-day administration of 5 micrograms/kg/day of soman sc on norepinephrine (NE) content, and catechol-O-methyl-transferase (COMT) and monoamine oxidase (MAO) activities of three rabbit tissues were examined. Effects on NE uptake by, and electrically stimulated release from, rabbit aorta were also determined, both in the 7-day study and with acutely applied soman. Tissues examined were the thoracic aorta, mesenteric artery, and brain stem. Significant (p less than 0.05) increases following 7 days of soman were observed in NE content: thoracic aorta, 20%; mesenteric artery, 48%; and brain stem, 121%. MAO activity decreased by 29% in the thoracic aorta, 20% in the mesenteric artery, and 48% in the brain stem. COMT activity also significantly decreased in two tissues, the thoracic aorta by 18% and brain stem by 23%. Acutely applied soman reduced electrically released NE from the thoracic aorta, but 7-day soman administration increased it. Seven-day soman administration, but not acutely applied soman increased NE uptake by the thoracic aorta. Thus, 7-day soman administration increased sympathetic capability by increasing NE content, nerve stimulation evoked NE release, and NE uptake, and by decreasing MAO and COMT activity. Therefore, repeated low-dose exposure to soman might exaggerate the response to any given level of sympathetic nerve stimulation and to NE-releasing agents.
Hu
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College of Pharmacy, University of Oklahoma, Health Sciences Center, Oklahoma City 73190.
Robinson
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CP
D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D004558:Electric Stimulation; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D009638:Norepinephrine / Q000493:pharmacokinetics*; D011817:Rabbits; D012999:Soman / Q000494:pharmacology*
D012999:Soman; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D009638:Norepinephrine