European journal of pharmacology
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Pregnant sheep and their fetuses were instrumented between 110 to 120 days of gestation (term, 145 days) for monitoring maternal and fetal arterial blood pressure, heart rate and blood flow in the maternal uterine and fetal intra-abdominal umbilical arteries. The administration of 2,5-dimethoxy-4-methylamphetamine (DOM, a 5-HT2 agonist) i.v. to the ewe in doses ranging from 1 to 20 micrograms/kg of ewe body weight produced dose-dependent decreases in the blood flow of the uterine and umbilical arteries. This was accompanied by an increase in the arterial blood pressure of the mother and fetus and a decrease in the fetal heart rate. ⋯ Ketanserin, a 5-HT2 antagonist (1 mg/kg), administrated 30 min prior to DOM significantly inhibited the reduction in blood flow in the uterine and umbilical arteries to DOM and blocked the increased vascular resistance in these vessels. The inhibitory effects of ketanserin on the responses to DOM in the uterine and umbilical arteries were surmountable. Our results indicate that DOM is a potent constrictor of the uterine and umbilical vasculature which may lead to fetal distress as evidenced by a decrease in fetal heart rate and arterial blood PO2. 5-HT2 receptor stimulation by DOM may be involved in these effects since they were blocked by ketanserin.
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The present study examined patterns of analgesia by intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of the serotonin 5-HT3 receptor agonist, 2-methylserotonin (1-100 micrograms) against acute thermal, mechanical or formalin-induced chemo-inflammatory pain in male rats. Neither i.c.v. or i.t. 2-methylserotonin produced motoric, sedative or respiratory effects. I.c.v. 2-methylserotonin was not analgesic at any dose in the pain assays employed. ⋯ The effects of 2-methylserotonin (100 micrograms) in the formalin test were attenuated by pretreatment (10 micrograms i.t.) with the 5-HT3 receptor antagonist MDL-72222, opioid antagonist naloxone or GABA antagonist bicuculline; the 5-HT2-receptor antagonist ketanserin or 5-HT1 receptor antagonist mianserin did not affect 2-methylserotonin-induced analgesia. In the thermal test, i.t. pretreatment with MDL-72222, ketanserin, naloxone or bicuculline, but not mianserin, reduced analgesic effects of 2-methylserotonin (100 micrograms i.t.). These findings suggest that spinal 5-HT3, opioid and GABA receptor systems interact to mediate acute chemo-inflammatory pain, and implicate the interaction of these systems with 5-HT2 receptor substrates in analgesia against acute thermal nociception.
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The effects of anaesthetic agents on pressor effect of NG-nitro-L-arginine (L-NNA), a potent inhibitor of nitric oxide (NO) synthesis, were examined in rats. I.v. bolus of L-NNA (1-32 mg/kg) in conscious rats dose dependently increased mean arterial pressure (MAP) to a maximum value of 53 +/- 2 mmHg at 16 mg/kg with ED50 value of 4.7 +/- 0.9 mg/kg. The effects of a single i.v. bolus dose (32 mg/kg) of L-NNA were examined in conscious rats and rats anaesthetised with pentobarbital, chloralose, ketamine, althesin (mixture of alphaxalone and alphadolone), urethane, enflurane or halothane. ⋯ The onsets were delayed in rats anaesthetised with pentobarbital, althesin, chloralose and enflurane but not altered with ketamine and urethane compared to that in conscious rats. Therefore, L-NNA caused intense and prolonged pressor response in conscious rats and rats anaesthetised with the i.v. anaesthetic agents pentobarbital, chloralose, ketamine, althesin and urethane. MAP effect of L-NNA was markedly attenuated by the inhalation anaesthetics halothane and enflurane.