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The effects of soman on the uptake and electrically induced release of norepinephrine (noradrenaline) from isolated human uterine artery have been investigated. Soman did not alter the uptake of norepinephrine by human uterine artery, but reduced the electrically induced release of norepinephrine from the artery. This reduced norepinephrine release may augment the fall in blood pressure induced by accumulated acetylcholine stimulating muscarinic receptors following cholinesterase inhibition.

Daily administration of soman for several days results in several alterations in the vascular neuroeffector system. To determine whether or not soman alters intracellular Ca2+ uptake, the effects of acute exposure to soman or 7-day administration of 5 micrograms kg-1 of soman on the capacity of microsomes and mitochondria from rabbit aortic vascular smooth muscle to take up 45Ca2+ were determined. Acute exposure to soman concentrations of 1-100 microM did not alter significantly (P greater than 0.05) 45Ca2+ uptake by either microsomes or mitochondria. On the other hand, 7-day soman administration markedly reduced (P less than 0.05) 45Ca2+ uptake by both microsomes and mitochondria. Thus, calcium uptake and intracellular calcium uptake-dependent responses will be affected by repeated soman administration.

The acute addition of 10 microM soman to rabbit aorta rings did not increase resting 45Ca2+ influx significantly in the absence or presence of 10 microM norepinephrine or 80 mM potassium (P greater than 0.05). However, agonist-induced 45Ca2+ influx into aorta rings from rabbits that received soman daily for 7 days was significantly reduced (P less than 0.05) compared to agonist-induced influx into rings from control rabbits. The resting influx of 45Ca2+ into aorta rings from 7 day soman-treated and control rabbits was not different (P greater than 0.05). The depression by soman of norepinephrine- and K(+)-induced 45Ca2+ influx may be due to adaptive changes resulting from the 7-day administration of soman.

Soman (pinacolyl methylphosphonofluoridate) not only increases acetylcholine levels by inhibiting cholinesterases, it also alters the levels of some other neurotransmitters including norepinephrine, dopamine, and serotonin. Soman also causes an alteration in the activities of the enzymes metabolizing norepinephrine when it is administered to animals. Because these alterations may result from indirect effects on the enzymes, the effects of in vitro application of soman on catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) activities in rabbit tissues were investigated. Enzyme activities were determined in rabbit lung, liver, cerebellum, cerebrum, brain stem, mesenteric artery, pulmonary artery, renal artery, central ear artery, thoracic aorta, and diaphragm. MAO and COMT activities were not affected by soman in any tissues tested, except the lung and liver, where the activity of COMT was increased (p less than 0.05). Thus, reported effects of soman in vivo on norepinephrine, dopamine, or serotonin concentrations, and MAO and COMT activities do not seem to result from direct effects on the activities of these amine-metabolizing enzymes.

The effects of soman (pinacolyl methylphosphonofluoridate), an organophosphorus cholinesterase inhibitor, on vascular contractility were examined on helically cut central ear arteries (CEA) or superior mesenteric arteries (M) from New Zealand White rabbits. Concentrations of soman up to 20 microM added cumulatively to arterial strips did not alter their resting tension. Concentrations of soman up to 10 microM also did not alter the tension responses to cumulatively added norepinephrine (NE), histamine, potassium (KCl), or serotonin (5-HT). Concentration-response curves obtained to each agonist initially, or 2 h later, did not differ in artery strips from control rabbits and those from rabbits given soman at 5 micrograms/kg sc daily for 7 d. Changes in responses to NE between the two time periods did differ in arteries from soman-treated and control rabbits in both the CEA and M, and to histamine in the M. Soman at 10 microM potentiated contractions to single concentrations of agonists in most cases. Soman at 10 microM also further increased the tension of strips already contracted by the agonists. Thus, although soman did not alter the concentration-response curves of the agonists at contracting rabbit arteries, it potentiated contractions to single concentrations of agonists both when added before the agonist and when added at the peak of the agonist-induced contraction. It also altered the rate of change with time of both M and CEA in responses to NE of artery strips from rabbits given soman at 5 micrograms/kg daily for 7 d.

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.

1. The effects of soman on the resting contractile tension of human uterine arteries, and on contractions of these arteries to vasoactive agents were investigated. 2. Soman did not alter the resting tension of helically-cut strips of human uterine arteries. 3. Soman did not alter concentration-response curves of the strips to noradrenaline, serotonin, potassium chloride or histamine. 4. Soman increased contractile tension of human uterine artery strips to subsequently added 1 microM noradrenaline. 5. It is possible that this enhancement may be involved in decreased regional blood flow following soman administration.