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Biomedical subjects

T Kubo

Publications and source records attributed to T Kubo.

At least 937 records · Page 52Linked to original sources

Pharmacological characterisation of the alpha-adrenoceptors responsible for a decrease of blood pressure in the nucleus tractus solitarii of the rat.

The effects of various alpha-adrenoceptor agonists, microinjected into the area of the nucleus tractus solitarii (NTS) at the level of the obex, on blood pressure, and the interaction between noradrenaline and some alpha-antagonists in the area of the NTS were investigated in anaesthetized male rats. A dose-dependent decrease in blood pressure was induced by noradrenaline. The relative potencies of the substances were adrenaline greater than noradrenaline greater than alpha-methylnoradrenaline greater than clonidine greater than tyramine. In contrast, phenylephrine was ineffective. The hypotensive effect of noradrenaline, alpha-methylnoradrenaline and clonidine was not affected by pretreatment with 6-hydroxydopamine given intraventricularly, while the effect of tyramine was blocked by the pretreatment. Prior application of phentolamine at the same site antagonized the hypotensive response to noradrenaline. Prazosin was about 10 times less potent than yohimbine in antagonizing the noradrenaline-induced hypotension. The present data suggest that the alpha-adrenoceptors in the area of the NTS responsible for the decrease in blood pressure are the same type as the peripheral presynaptic alpha 2-adrenoceptors but may be located postsynaptically. It appears that the noradrenergic neurons in the NTS can play a role in blood pressure regulation.

Adrenergic alpha-Agonists↗

Comparative studies of (--)-, (+/-)-propranolol, atenolol, guanethidine, bretylium and tetracaine on adrenergic transmission.

1 Effects of (--)-, (+/-)-, and (+)-propranolol, atenolol, guanethidine, bretylium and tetracaine were studied on relaxation responses of rabbit ileum and contractile responses of rabbit pulmonary artery and guinea-pig vas deferens to electrical nerve stimulation (2 to 50 Hz). 2 In the ileum, inhibition by tetracaine 3.3 x 10(-6) M occurred at high frequencies of stimulation, while bretylium 1.2 x 10(-4) M and guanethidine 2 x 10(-5) M inhibited responses at all frequencies, the latter producing greater inhibition at low frequencies. 3 (+/-)-Propranolol 10(-5) M produced a tetracaine-type inhibition after 1 h and a bretylium-pattern after 2 h in the ilea and pulmonary arteries and a transition from bretylium- to guanethidine-pattern in the vas deferens, while atenolol 2 x 10(-5) to 10(-4) M produced guanethidine-type inhibition in all preparations. 4 (--)-, (+/-)-, and (+)-Propranolol 3 x 10(-6) to 3.3 x 10(-5) M were equipotent in the vas deferens and ileum. However, inhibition by (--)-propranolol 3.3 x 10(-5) M persisted in the ileum, while that by the (+)-isomer was partially restored by washing. 5 (--)- or (+)-Propranolol 3.3 x 10(-5) M or atenolol 2 x 10(-5) M did not inhibit relaxation of the ileum after the bath temperature was maintained at 4 degrees C for 2 h during drug application. 6 In conclusion, propranolol and atenolol both have gradually developing guanethidine-like adrenergic neurone blocking actions.

Animals↗

Cardiovascular responses to intracisternal administration of nicotine in rats.

The administration of nicotine into the cisterna magna evoked a delayed depressor effect with an initial pressor effect in anaesthetized rats. The depressor response was accompanied by a bradycardia. The cardiovascular effects of nicotine were abolished after intracisternal administration of hexamethonium but not after atropine given via the same route. Intravenous administration of methylatropine abolished the bradycardic response to nicotine but did not affect the blood pressure responses. The pressor effect of nicotine was abolished by intravenous administration of phenoxybenzamine. The cardiovascular effects of nicotine injected intracisternally were abolished when the diffusion of nicotine onto an area around the area postrema was interrupted using a polyethylene tube. In contrast, nicotine applied to the area produced a marked pressor--depressor response. It is concluded that the cardiovascular responses to intracisternal administration of nicotine result from the activation of central nicotinic receptor sites that may be present around the area postrema.

Animals↗

Head and eye movements following vestibular stimulus in squirrel monkeys.

Head and eye movements induced by vestibular stimuli (rotational velocity steps) were studied under several experimental conditions in squirrel monkeys. Monkeys showed prominent head nystagmus under a free head condition. Slow phase gaze velocity (SPGV) was calculated by summing the slow phase speed of coupled head and eye nystagmus. A statistical test showed no significant difference between slow phase eye velocities in a fixed head versus SPGV in a free head condition. This indicates that an accurate negative feedback control of eye movements is performed by the vestibular system when sensing active head movements. Bilateral lateral semicircular canal block eliminated these responses in subjects without amphetamine injection. However, in amphetamine-injected animals, 14-21% of preoperative response could be found even after this operation. Since the plane of rotation was not parallel to that of the lateral semicircular canals, the result was considered to be due to vertical semicircular canal stimulation.

Animals↗

Antihypertensive effects of nifedipine on conscious normotensive and hypertensive rats.

Hypotensive actions of single and repeated administrations of nifedipine were evaluated in comparison with hydralazine in normotensive, spontaneously hypertensive and renal hypertensive rats. Substantial and prolonged falls in blood pressure were observed following oral dosing with 3 mg/kg of nifedipine in renal hypertensive rats, with 10 mg/kg of nifedipine in normotensive and spontaneously hypertensive rats and with 10 mg/dg of hydralazine in all three groups of animals. The hypotensive effect of nifedipine was greater in both forms of hypertensive rats than the normotensive rats, while there was no difference in the hypotensive effect of hydralazine in normotensive and hypertensive animals. In spontaneously hypertensive rats tolerance to nifedipine and hydralazine was not observed with oral administrations for 4 weeks at a daily dose of 10 mg/kg. An increase in heart rate always accompanied the hypotension induced by both drugs, but this tachycardia was seen to a lesser extent with nifedipine than with hydralazine. The mechanism of the selective action of nifedipine in hypertensive rats in contrast to normotensive rats is discussed.

Animals↗

Increased pressor responses to nicotine in spontaneously hypertensive rats.

Intraventricular administration of nicotine produced a biphasic effect, consisting of an initial rise than a slight fall in blood pressure in unanaesthetized rats. Spontaneously hypertensive rate (SHR) showed increased pressor responses, but these responses were within normal limits in renal hypertensive and DOCA-saline hypertensive rats. The blood pressure response to nicotine in SHR was abolished by intraventricular administration of hexamethonium, but not by atropine given via the same route. Central phentolamine and 6-hydroxydopamine did not affect the pressor response to nicotine. The pressor effect of nicotine in SHR was markedly diminished after removal of the adrenals and abolished after bilateral adrenalectomy plus peripheral 6-hydroxydopamine. These results indicate that the pressor response to intraventricular nicotine is increased in SHR. The pressor effect of nicotine may result from the activation of the central nicotinic receptor sites, which may cause the release of catecholamines both from the adrenal medulla and adrenergic nerve terminals.

Adrenalectomy↗

Intracardiac pressures in pregnant patients with mitral stenosis.

The influences of pregnancy on the pulmonary circulation in mitral stenosis (MS), were studied. 1) Twenty-two cardiac patients underwent serial right heart catheterization with the use of flow-directed catheter without X-ray fluoroscopy during the course of pregnancy. 2)In 23 cases of MS, in whom cardiac catheterization had been performed before pregnancy, clinical courses during the pregnancy were studied. In the 26-32 weeks' gestation: in MS (Group I), an elevation of peak systolic pulmonary arterial pressure (s-PAP) (mean + 14.9 mmHg, P less than 0.001) was seen; in contrast, in atrial septal defect (Group II), s-PAP remained constant. Right atrial pressure rose in the 26-32 weeks, gestation in both the groups. Infusion of 200 ml of dextran in 12-16 weeks, gestation induced an elevation of s-PAP in Group I, especially in those who fell into heart failure in the succeeding courses of pregnancy; but not in Group II. In MS, in 12 cases, whose s-PAP before the pregnancy was below 35 mmHg, no heart failure occurred during the pregnancy; in 6 of 8 cases with s-PAP between 35 and 50 mmHg, mild heart failure occurred; and in 2 cases with s-PAP over 50 mmHg, severe heart failure occurred during the pregnancy. In conclusion, in MS, PAP rises during pregnancy, and S-PAP before pregnancy and the reaction to dextran infusion can give suggestions for allowing pregnancy.

Adult↗

Adrenergic transmission failure via the blockade of presynaptic beta receptors in guinea-pig pulmonary arteries.

Mechanisms related to the inhibitory actions of low concentrations of l- and d-propranolol on adrenergic transmission were investigated in isolated preparations of guinea-pig pulmonary arteries. In sympathetic nerve-radial muscle preparations, l-propranolol (3.3 X 10(-8) and 10(-7) M) dose-dependently inhibited by 15 to 20% contractile responses to nerve stimulation (1 Hz, 2-msec pulse width, 100-sec period and 30-min intervals) 30 and 60 min after the addition, whereas 3.3 X 10(-7) M produced a maximal inhibition. Contractile responses to cumulatively applied norepinephrine were not modified by pretreatment with l-propranolol (10(-7) - 10(-6) M). d-Propranolol (10(-7) M) produced no inhibition of adrenergic transmission. In superfused spiral preparations preloaded with [3H]norepinephrine, l-isoproterenol (3 X 10(-8) - 10(-6) M) dose-dependently facilitated total 3H efflux by transmural field stimulation by 10 to 35% under the same conditions; this facilitation was antagonized by l-propranolol (10(-7) M) but not by d-propranolol (10(-7) M). Phentolamine (3 X 10(-6) M) increased 3H efflux by approximately 3-fold. In the presence of phentolamine, l-propranolol (10(-7) M) significantly inhibited 3H efflux, whereas d-propranolol (10(-7) M) produced no effect. Presynaptic beta adrenoceptors are present on sympathetic nerve endings which innervate guinea-pig pulmonary arteries and low concentrations of propranolol inhibit adrenergic transmission via blockade of these receptors.

Adrenergic beta-Antagonists↗

Geographical pathology of gastric carcinoma: a comparative study on histological types between high and low mortality areas in Japan.

A histological comparison of 1,687 cases of gastric carcinoma in Niigata, a high mortality prefecture for this cancer, and 954 cases in Kagoshima, a low mortality area, was carried out in order to investigate whether or not this difference in mortality reflects any change of histological type of gastric carcinoma. In both series, in both males and females , the proportion of adenocarcinoma increased with increase of the patients' age, while that of diffuse carcinoma decreased. When data from the two prefectures were compared, there was no significant difference in age group distribution of each histological type. It appears that the same histological types of gastric carcinoma occur throughout Japan.

Adenocarcinoma↗

Geographical pathology of gastric carcinoma: histological types among Chileans.

Nine hundred and twenty-three Chilean cases of gastric carcinoma who had received surgical resection of the stomach were histologically classified. In both males and females, diffuse carcinoma was a common type among younger patients, while adenocarcinoma was predominant in elderly patients. Statistical analysis demonstrated identical type distributions in all age groups in the Chilean series, as was seen in other ethnic groups surveyed previously.

Adenocarcinoma↗