British journal of pharmacology
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1. The effects of indomethacin were investigated on haemodynamics, haematological and blood glucose values, and the release of tumour necrosis factor (TNF), platelet activating factor (PAF) and eicosanoids in anaesthetized pigs receiving 5 micrograms kg-1 E. coli lipopolysaccharide (LPS) over 60 min into the superior mesenteric artery. The animals were observed for an additional period of 2 h after the termination of LPS infusion. 2. ⋯ Concentrations of cyclo-oxygenase products studied were reduced by the end of the observation period, whereas LTB4 production was unaffected.6. The decrease in MABP induced by exogenous PAF was temporarily prevented by indomethacin.7. These data indicate that the beneficial effect of indomethacin in LPS-induced septic shock is related to cyclo-oxygenase inhibition as well as to a direct vasoconstrictor property of the drug.
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Changes of quantal transmitter release caused by gadolinium ions at the frog neuromuscular junction.
1. The actions of the trivalent cation, gadolinium (Gd3+), were studied on frog isolated neuromuscular preparations by conventional electrophysiological techniques. 2. Gd3+ (450 microM) applied to normal or formamide-treated cutaneous pectoris nerve-muscle preparations induced, after a short delay, a complete block of neuromuscular transmission. ⋯ Gd3+, in concentrations higher than 100 microM, decreased reversibly the amplitude of m.e.p.ps suggesting a postsynaptic action. 8. It is concluded that the block of nerve-impulse evoked quantal release caused by Gd3 + is related to its ability to block the calcium current entering the nerve endings, supporting the view that Gd3 + blocks N-type Ca2+ channels; while the enhancement of spontaneous quantal release is probably the result of Gd3 + entry into motor nerve endings. Besides its dual prejunctional effects on quantal release it is suggested that Gd3 + exerts a postsynaptic action on the endplate acetylcholine receptor-channel complex.
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Comparative Study
Cardiovascular profile of 5 novel nitrate-esters: a comparative study with nitroglycerin in pigs with and without left ventricular dysfunction.
1. Four cumulative 10 min intravenous infusions of 0.05, 0.2, 0.5 and 2.0 mg min-1 were used to compare the cardiovascular profile of 5 novel nitrate-esters dissolved in Intralipid 10% to that of nitroglycerin (GTN) in conscious pigs. 2. Infusion of Intralipid 10% alone had no effect on any of the systemic haemodynamic parameters. ⋯ At this dose, GTN also caused vasodilatation in the vascular beds of the brain, kidneys and adrenals. With CEDO 8956 no significant changes were achieved. 9. We conclude that the cardiovascular profile of CEDO 8956 in both normal animals and in animals with chronic left ventricular dysfunction warrants further study on its usefulness in the treatment of a number of cardiovascular disorders.
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1. A series of experiments was performed in conscious, unrestrained, male, Long Evans rats, chronically instrumented for the measurement of regional haemodynamics. 2. Infusion of glyceryl trinitrate (GTN, 0.1 mg kg-1 min-1, i.v.) for 10 min elicited tachycardia, but no sustained change in mean arterial blood pressure. ⋯ However, since the effects of enalaprilat were more marked than those of captopril (in spite of the dose of both drugs being supramaximal for inhibition of angiotensin-converting enzyme), other factors must have been involved. 6. In a separate experiment, pretreatment with the nitric oxide synthesis inhibitor, N0-nitro-L-arginine methyl ester (1 mg kg- 1 h-1, i.v.), enhanced the mesenteric vasodilator effect of molsidomine. Collectively, these results are consistent with in vitro data showing that endogenous nitric oxide can inhibit the vasodilator effects of nitric oxide derived from molsidomine, and that the sulphydryl groups of captopril can protect endogenous nitric oxide from inactivation by oxygen-derived free radicals, thereby enhancing the inhibitory effect of endogenous nitric oxide on the vasodilator responses to exogenous nitric oxide derived from molsidomine (or GTN).
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1. Chronic treatment with the dihydropyridine calcium channel antagonist, nitrendipine, given concurrently with ethanol, prevented the ethanol withdrawal syndrome in mice, even though the chronic nitrendipine treatment was stopped 24 h or 48 h before the withdrawal testing. 2. This effect was seen in two strains of mice with different methods of ethanol administration. ⋯ Chronic nitrendipine treatment did not affect the seizure threshold to bicuculline in mice that were not given ethanol. 7. Whole brain concentration measurements showed that the effects were not due to residual nitrendipine in the CNS at the time of withdrawal testing or to differences in central ethanol concentrations during the treatment. 8. It is suggested that the results provide evidence for a functional role for dihydropyridine-sensitive calcium channels in ethanol dependence.