Biomedical subjects
Publications and source records attributed to T Endo.
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The rabbit pulmonary artery contains postsynaptic alpha-adrenoceptors which meidate smooth muscle contraction; its noradrenergic nerves contain presynaptic alpha-adrenoceptors which mediate inhibition of the release of the transmitter evoked by nerve impulses. Dose-response curves for the pre- and postsynaptic effects of eight alpha-receptor agonists were determined on superfused strips of the artery in the presence of cocaine, corticosterone and propranolo. 1. According to the concentrations which caused 20% of the maximal contraction (EC20 post), the postsynaptic rank order of potency was: adrenaline greater than noradrenaline greater than oxymetazoline greater than naphazoline greater than phenylephrine greater than tramazoline greater than alpha-methylnoradrenaline greater than methoxamine. The pA2 values of phentolamine againstoxymethazoline, phenylephrine, alpha-methylnoradrenaline and methoxamine were 7.43, 7.48, 7.59 and 7.69, respectively. 2. For the investigation of presynaptic effects, the arteries were preincubated with 3H-noradrenaline. All agonists inhibited the overflow of tritium evoked by transmural sympathetic nerve stimulation. According to the concentrations which reduced the stimulation-induced overflow by 20% (EC20 pre), the rank order of potency was: adrenaline greater than oxymetazoline greater than tramazoline greater than alpha-methylnoradrenaline greater than noradrenaline greater than naphazoline greater than phenylephrine greater than methoxamine. 10(-5) M phentolamine shifted the presynaptic dose-response curves for moradrenaline and oxymethazoline to the right. 3. The ratio EC20 pre/EC20 post was calculated for each agonist as an index of its relative post- and presynaptic potency. According to the ratios, the agonists were arbitrarily classified into three groups. Group 1 (ratio about 30: preferentially postsynaptic agonists) comprised methoxamine and phenylephrine; group 2 (ratio near 1; similar pre- and postsynaptic potencies) comprised noradrenaline, adrenaline and naphazoline; group 3 (ratio below 0.2; preferentially presynaptic agonists) comprised oxymetazoline, alpha-methylnoradrenaline and tramazoline (as well as clonidine). 4. Preferentially presynaptic and preferentially postsynaptic agonists had opposite effects on the basoconstrictor response to nerve stimulation. Methoxamine and phenylephrine either did not change or enhanced, but never reduced, the response. In contrast, oxymetazoline, alpha-methylnoradrenaline and tramazoline at low concentrations selectively inhibited the response to stimulation at low frequency (0.25-2Hz). 5. It is concluded that alpha-adrenoceptor agonists vary widely in their relative pre- and postsynaptic potencies, possibly because of structural differences between pre- and postsynaptic alpha-receptors. Pre- and postsynaptic components contribute to their overll postsynaptic effec in actively transmitting synapses. The preferential activation of presynaptic alpha-receptors results in alpha-adrenergic inhibition of synaptic transmission.
Strips of the rabbit main pulmonary artery were preincubated with 3H-noradrenaline. 3 X 10(-8) -- 10(6) M yohimbine enhanced the overflow of tritium and the smooth muscle contraction induced by transmural sympathetic nerve stimulation. The increase of the stimulation-evoked overflow of tritium was prevented by a high concentration of oxymetazoline. The results indicate that yohimbine is more potent in blocking the presynaptic than the postsynaptic alpha-adrenoceptors of the artery.
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The effects of maprotiline, mainly on the CNS, were examined and compared with those of imipramine, methamphetamine and chlorpromazine. In the repeated administration and the stroboscope studies, maprotiline exhibited actions to increase behavioral activities of animals, just like amphetamine and imipramine. This appears to attest to pharmacological effects of maprotiline as an anti-depressant. It is noted, however, that whereas maprotiline shows a slight anti-apomorphine action in dogs and an inhibition of the spinal reflex action potential in cats, such actions are not recognized in other anti-depressants of the tricyclic groups including imipramine, amitriptyline, etc. These differences suggest the tranquilizing action of maprotiline at work, probably forming a specific pharmacological feature of maprotiline. Also, maprotiline increases body weight of rats strikingly, which seems to offer a wide range of clinical applications of this drug.
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The results of investigations done in 1965, 1966, and 1972 on the workload of motormen of high-speed trains operating on railroads with maximum speeds of 210 km/hr were compared in an attempt to discuss the physiological implications of the driving task. The driving time of a 515 km section was 4 hr in 1965 and was lowered to 3 hr 10 min since 1966 for the fastest super-express trains. The mean heart rate was maintained around 80 beats/min during the entire driving period in 1965, but declined gradually in 1966 or 1972. Although in 1966 the operations at constant high speed appeared to favor cerebral activities, drivers in the 1972 investigation not only showed lowered perceptual and choice reaction performances but also experienced significant increase in errors in detecting signal tones given as a subsidiary task. Polygraphic recordings in 1972 indicated that drivers sometimes fell into drowsing of short duration intermittently, accompanied by temporary drop in heart rate, absence of controller action, and increase of detection errors. These effects were dominant in periods after 90 min of driving. The need to reduce the monotomy effects during underloaded train driving is suggested.
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