Peripheral inhibition of reflexogenic vasodilation induced by veratridine.
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The development of adren- and cholinergic nervous plexuses in the brain base arteries was studied by histochemical methods of Falck and Kelle in animals and fetuses of 10-22 days, newborn rats, animals of 10, 20, 30, 40, 60 and 120 days of life and 1 and 2 years old rats. The cholinergic nerve fibres were first found in the basilar, vertebral and internal carotid arteries on the 15th and 16th days of ontogenesis. Specific fluorescence of adrenergic conductors on the same arteries is revealed somewhat later--from the 17th and 18th days of the intrauterine development. Further formation of the cholin- and adrenergic innervation of the arteries of the Willis' circle goes on synchronously. The number of nerve fibres increases with the growth of the artery diameter. The concentration of catecholamines and the activity of AChE in them gradually increases. The greatest density of nerve fibres per 1 mm2 is determined in 20-day-old rats. The number of cholinergic nerve fibres on the arteries of the brain base is equal to that of adrenergic fibres during the whole period of postnatal ontogenesis. By the 30th day the effector nervous apparatus has a definite structure. In old rats the activity of AChE and the content of catecholamines drop, the amount and concentration of nerve fibres decrease.
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Plasma concentrations of nasally administered ipratropium bromide were analyzed in 10 subjects suffering from severe vasomotor rhinitis and 10 age-sex matched control subjects. The rate of salivary secretion and heart rate were monitored in order to measure systemic anticholinergic effects. A total dose of 360 micrograms of ipratropium bromide (60 micrograms into each nostril, repeated twice at 15 min intervals) were administered nasally to the subjects in randomized order. Ipratropium bromide was rapidly absorbed from the nasal mucosa into the systemic circulation in both groups. The peak plasma concentrations were detected within 10 min after the last drug administration. The peak concentrations were about 50% higher (380 +/- 153 pg/ml) in patients than in control subjects (245 +/- 134 pg/ml). The AUCs/0-15 min (1970 +/- 1140 pg/ml X min) in patients were about 100% higher than in the control subjects (960 +/- 560 pg/ml X min). During the experiment there was a small decrease in the heart rate (8 bpm) and salivary secretion (10%) in both groups. In conclusion, the vasomotor rhinitis increases the systemic absorption of nasally administered ipratropium bromide, but the small increase in the absorption is not likely to have any clinical consequences.
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