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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 685 records · Page 38Linked to original sources
PubMed1986

Centrally induced cardiovascular and sympathetic responses to adrenocorticotrophic hormone.

To investigate the effects of adrenocorticotrophic hormone on central cardiovascular regulation, an intracerebroventricular injection of the drug was given to male Wistar rats. With doses of 1 microgram and 10 micrograms per rat, blood pressure began to rise within 1 min, attaining a maximum value 5-10 min later. Both heart rate and abdominal sympathetic nerve activity increased simultaneously with the rise in blood pressure. Injection into the fourth ventricle or intravenous administration of the drug elicited no appreciable cardiovascular responses. These results suggest that endogenous adrenocorticotrophic hormone produced locally in the hypothalamus may participate in central cardiovascular regulation by increasing sympathetic outflow.

Action Potentials↗
PubMed1986

Cardiovascular and sympathetic responses to ouabain injected into the hypothalamus in rats.

To investigate the effects of sodium-potassium activated adenosine triphosphatase inhibition on central cardiovascular regulation a microinjection of ouabain was given into the hypothalamus of urethane anaesthetised rats. Doses of 0.01-1.0 micrograms per rat injected into the posterior hypothalamus produced a rise in blood pressure within 1 min, the maximum rise occurring 15-20 min later in a dose dependent manner. Both heart rate and abdominal sympathetic nerve activity increased with the rise in blood pressure. Ouabain injected into either the anterior preoptic hypothalamus or the ventromedial hypothalamus produced no notable cardiovascular responses. These results suggest that an endogenous digitalis like substance produced in the hypothalamus as a result of sodium loading may participate in central cardiovascular regulation by increasing sympathetic outflow in the discrete area of the brain, as does ouabain.

Action Potentials↗
PubMed1986

A neuroendocrine (Merkel) cell carcinoma with coexisting intraepidermal squamous cell carcinoma of the skin. Its growth accelerated by an extrinsic factor.

A case of neuroendocrine (Merkel) cell carcinoma with coexisting intraepidermal squamous cell carcinoma of the skin was studied histologically, immunohistochemically and ultrastructurally as well as with tissue-culture and transplantation into nude mice. The primary tumor found in the lower leg of a 68-year-old Japanese man had remained thumb-sized for five years and, after contusion, had begun to enlarge rapidly up to 5 cm in size during one month. The patient died of metastatic neuroendocrine cell carcinoma nine months after excision of the primary tumor. Histologically the primary tumor was composed of neuroendocrine cell carcinoma extending down to subcutaneous adipose tissue and a small amount of intraepidermal squamous cell carcinoma, not associated with a wide range of necrosis, hemorrhage, granulation tissue or fibrosis. The tumor cells of the former were diffusely positive for neuron-specific enolase. They contained a few secretory granules, 100 nm in diameter. The tumor cells both cultured in media and transplanted into nude mice died two months later. The present case is the first report of Merkel cell carcinoma in which the growth accelerated by an extrinsic factor was proved. Histogenesis of neuroendocrine cell carcinoma with coexisting squamous cell carcinoma is also discussed.

Adenocarcinoma↗
PubMed1986

Afterhyperpolarization mechanisms in cat sympathetic preganglionic neuron in vitro.

A long-lasting afterhyperpolarization (AHP) follows the antidromic or current-induced action potential of sympathetic preganglionic neurons (SPNs) studied in slices of cat spinal cord maintained in vitro. Duration and amplitude of the AHP that follows a single spike were 2.8 +/- 0.3 s and 16.0 +/- 0.7 mV (mean +/- SE), respectively. In most cases two components could be distinguished, an initial faster and usually larger component [fast (F) AHP] followed by a slowly decaying component [slow (S) AHP]. An increase in membrane conductance was associated with the AHP. The amplitude of both components increased with membrane depolarization and decreased with hyperpolarization. Both fast and slow component were nullified at a voltage of -90 mV in 3.6 mM K+. Peak AHP amplitude decreased as K+ was increased from 1.5 to 7.0 mM. The null point for both fast (F) AHP and slow (S) AHP shifted in the depolarizing or hyperpolarizing direction when K+ was increased or decreased, respectively. These data suggest that an increase in K+-conductance is the mechanism underlying the AHP. The two components of the AHP could be separated by their differential sensitivity to superfusion with the Ca2+-channel blocker cobalt (2 mM) or with low Ca2+ (0.25 mM). These procedures resulted in an AHP of much shorter duration (330 ms, range 150-600), presumably the FAHP. These observations indicate that a Ca2+-activated K+-conductance is likely to be involved in the generation of the SAHP. The FAHP was depressed during superfusion with tetraethylammonium (TEA) (20 mM) and intracellular cesium injection. The SAHP was enhanced by TEA and enhanced or depressed by cesium. In 3.6 mM K+ the FAHP reversed in polarity at membrane voltages more negative than -90 mV. This component had an approximately linear relation of amplitude to membrane potential. The SAHP did not reverse in most cells. In the few cases in which it reversed, the change in amplitude for a given change in membrane voltage was much smaller on the negative than on the positive side of the null potential. Thus the SAHP shows voltage-dependent, nonlinear characteristics. This difference in behavior of the two components was also observed when the null point was displaced in high or low K+. In the presence of tetrodotoxin (TTX) the AHP persisted in temporal association with a high-threshold, TTX-resistant, cobalt-sensitive spike. During the time course of the AHP the efficacy of synaptic input decreased, suggesting that the AHP has an important role in regulating the firing rate of the SPN.

Action Potentials↗
PubMed1986

Attenuated development of hypertension by chronic administration of bromocriptine in Doca-salt hypertensive rats.

The aim of the study was to investigate whether or not the development of hypertension is influenced by chronic treatment with bromocriptine and/or domperidone. Rats treated with DOCA-salt were divided into 4 groups: control with vehicle, bromocriptine, bromocriptine with domperidone, and domperidone. Increased blood pressure by DOCA-salt treatment was significantly suppressed by treatment with bromocriptine and this bromocriptine suppression was significantly blocked by treatment with domperidone. Increased urinary excretion of norepinephrine by DOCA-salt treatment was significantly suppressed by bromocriptine and the inhibiting effect of bromocriptine disappeared with domperidone. In the four groups of rats, there were significant correlations between systolic blood pressure and urinary excretion of norepinephrine, systolic blood pressure and urinary excretion of epinephrine, and urinary excretion of dopamine and sodium. These results suggest that the chronic effect of bromocriptine is to suppress development of DOCA-salt hypertension, mainly through peripheral mechanisms which are involved in the decreased release of norepinephrine.

Animals↗
PubMed1986

Hypotension and hypothalamic depression produced by intracerebroventricular injections of GABA in spontaneously hypertensive rats.

To determine the central effects of 4-Amino-n-butyric acid (GABA), pressor and sympathetic nerve responses to electrical stimulation of the ventromedial hypothalamus were recorded following the intracerebroventricular (ICV) injection of GABA. In normotensive Wistar rats, anesthetized with urethane, ICV injections of GABA (50-200 micrograms) reduced sympathetic nerve activity, arterial blood pressure, and heart rate in a dose-dependent manner. Graded electrical stimulation of the ventromedial hypothalamus (50, 100, 150 microA) increased not only mean blood pressure but also the rate of sympathetic nerve firing, and both responses were attenuated by GABA pretreatment (100, 200 micrograms, ICV). In spontaneously hypertensive rats (SHR), ICV-injected GABA also reduced sympathetic and cardiovascular activity, but the magnitude of depressor responses was significantly larger in SHR than in normotensive Wister Kyoto controls (WKY). Pressor and sympathetic nerve responses elicited by ventromedial hypothalamic stimulation were initially larger in SHR than in WKY, but upon subsequent ICV injection of GABA, hypothalamic responsiveness in SHR was inhibited more prominently and became comparable to that in WKY. These results suggest that by depressing hypothalamic function, centrally injected GABA decreases sympathetic nerve activity to thereby lower blood pressure and heart rate, and in SHR, ICV-injected GABA reversed hypothalamo-sympathetic hyperactivity and thus attenuated hypertension.

Animals↗
PubMed1986

Hypotensive responses to centrally administered taurine in DOCA-salt hypertensive and spontaneously hypertensive rats.

The present study was designed to investigate the short-term effects of intracerebroventricularly-administered taurine in DOCA-salt hypertensive (DOCA), spontaneously hypertensive (SHR) and their respective normotensive control rats anesthetized with urethane. Blood pressure, heart rate and sympathetic nerve activity were consistently decreased following the injection of taurine 150 micrograms per rat in hypertensive rats as well as in normotensive controls of the two groups. Percent changes from the baselines in blood pressure, heart rate and sympathetic nerve activity were significantly larger in DOCA-salt hypertensive rats than those in sham operated rats. In contrast, percent changes in blood pressure and sympathetic nerve activity were not significantly different between spontaneously hypertensive rats and normotensive wistar kyoto rats. These result show that the responses of blood pressure, heart rate and sympathetic nerve activity to intracerebroventricular taurine are different between spontaneously hypertensive rats and DOCA-salt hypertensive rats. It appears that augmented vasodepressor responses to taurine in DOCA-salt hypertensive rats, as compared to spontaneously hypertensive rats, are due to enhanced inhibition of the sympathetic outflow.

Animals↗
PubMed1986

Enhanced renal sympathetic nerve activity in response to salt loading in rats.

To analyze the conflicting data on the relationship between sodium intake and sympathetic activity, the effects of a chronically excessive intake of sodium on renal sympathetic activity and blood pressure were investigated in normotensive rats. Renal sympathetic activity was estimated by urinary excretion of free norepinephrine (NE) and the turnover of NE in the kidneys. Blood pressure increased in rats receiving a high sodium diet when compared with that of the basal sodium diet. Urinary-free NE, epinephrine (E) and dopamine (DA) excretions in rats receiving a high sodium diet were enhanced significantly from those in the basal sodium diet. The turnover of NE in the kidneys was more enhanced in the high sodium group than in the basal sodium group. By blocking the sympathetic tone with ganglionic blockade, hexamethonium, enhanced excretion of urinary NE and elevation of blood pressure in response to salt loading were blocked to the levels of the basal sodium diet. These results suggest that a chronically excessive intake of sodium enhances the renal sympathetic and adreno-medullary activities, leading to a rise in blood pressure in normotensive rats.

Animals↗
PubMed1986

The significance of duration of salt loading on cardiovascular response and urinary excretion of catecholamine in rats.

To analyze the conflicting data on the relationship between sodium intake and catecholamine release, the effect of the duration of high sodium loading on cardiovascular response and catecholamine release was examined in conscious rats. Urinary excretions of norepinephrine (NE), and dopamine (DA) were measured frequently over a 4 week period. Male Wistar rats at 4 weeks of age were given a diet containing either basal (0.3%) or high (3.1%) sodium content. Systolic blood pressure was measured weekly by the tail cuff method. Twenty-four hour urine collections were made for analysis of catecholamines in metabolic cages every other day during the initial 2 weeks and once a week in the following 2 weeks of salt loading. High sodium intake resulted in a rise in blood pressure and a reduction in heart rate. Bradycardia was significant during the initial 2 weeks and not significant during the following 2 weeks after the initiation of salt loading. Urinary excretion of NE did not change during the initial 2 weeks of salt loading but increased significantly following the 2 week period after salt loading. Urinary excretion of DA increased diphasically, showing the first peak at 1 week after salt loading and the second peak at 4 weeks after the initiation of salt loading. These results suggest that the heart rate and urinary excretion of catecholamine are influenced by the duration of salt loading. When we estimate the effect of salt loading on cardiovascular response and urinary excretion of catecholamine, we should draw attention to the importance of the duration of salt loading, because this duration of time further elicites delayed response in the sympathetic nervous system.

Animals↗
PubMed1986

Acute effects of captopril on the baroreflex of normotensive and spontaneously hypertensive rats.

When captopril was injected intravenously in urethane anesthetized rats, a hypotensive effect accompanied by bradycardia was obtained, while an intravenous (i.v.) injection of prostaglandin I2 (PGI2), which induced hypotension of the same magnitude as the hypotensive effect obtained with captopril, caused a marked tachycardia. Simultaneously, sympathetic nerve activity recorded from abdominal sympathetic nerves was unchanged following injection of captopril, while it was significantly increased during hypotension induced by PGI2. The bradycardia, but not the hypotensive effects induced by captopril was abolished by i.v. pretreatment with atropine. Intracisternal injection of a small dose of captopril inhibited reflex tachycardia during hypotension induced by PGI2 and prolonged the hypotensive effect, while intravenous administration of this dose did not inhibit the reflex tachycardia induced by PGI2. In spontaneously hypertensive rats (SHR), the hypotensive effect of captopril was increased partly, however, the accompanying bradycardia was significantly reduced. These findings suggest that captopril inhibits the baroreflex and centrally activates the cardiac vagal nerve. Moreover in SHR, the effect of captopril on cardiac vagal activity was disturbed.

Animals↗
PubMed1986

Central GABA-ergic stimulation attenuates hypertension and hypothalamic hyperactivity in spontaneously hypertensive rats.

When GABA (4-amino-n-butyric acid, 50-200 micrograms) was injected into the lateral ventricle of urethane-anaesthetized Wistar rats, sympathetic nerve activity, arterial pressure and heart rate were decreased dose-dependently. Graded electrical stimulation of the ventromedial hypothalamus (50, 100 and 150 microA) increased not only mean blood pressure but also the rate of sympathetic nerve firing, and both responses were attenuated by GABA pretreatment (100 and 200 micrograms, i.c.v.). In spontaneously hypertensive rats (SHR), i.c.v.-injected GABA also reduced sympatho-cardiovascular activity, but the magnitude of the depressor responses was significantly larger in SHR than in normotensive Wistar-Kyoto (WKY) control rats. Pressor and sympathetic nerve responses elicited by hypothalamic stimulation were initially larger in SHR than in WKY rats. However, upon subsequent i.c.v. injection of GABA, hypothalamic responsiveness in SHR was inhibited more prominently and became almost the same as that in WKY rats. These results suggest that, by depressing hypothalamic function, central GABA-ergic stimulation decreases sympathetic nerve activity thereby lowering blood pressure and heart rate. Because of the increased central sensitivity in SHR, GABA-ergic stimulation reversed hypothalamo-sympathetic hyperactivity and attenuated hypertension.

Animals↗
PubMed1986

Augmented vasodepressor and sympathetic responses to intracerebroventricular injections of diltiazem, a calcium channel blocker, in DOCA-salt hypertensive rats.

The role of the calcium ion in central cardiovascular regulation was investigated by injecting a calcium channel blocker, diltiazem, intracerebroventricularly (i.c.v.) in urethane-anaesthetized, DOCA-salt hypertensive rats. This produced a fall in blood pressure and bradycardia with corresponding decreases in abdominal sympathetic nerve activity. However, a similar amount of diltiazem injected intravenously (i.v.) did not affect abdominal sympathetic nerve activity despite an accompanying vasodepression. The responses to i.v. injections of diltiazem were not different between the two groups; however, the magnitude of the blood pressure fall, bradycardia and sympathetic inhibition with i.c.v. injections was greater in the DOCA rats than in the sham-operated animals. These results suggest that diltiazem causes the central nervous system to decrease the sympathetic nerve outflow. The augmented central vasodepressor responses to diltiazem in DOCA-salt hypertensive rats may indicate that calcium metabolism in the central nervous system is disrupted and that this is of importance in the pathogenesis of DOCA-salt hypertension in rats.

Animals↗
PubMed1986

Evidence for a digitalis-like substance in the hypothalamo-pituitary axis in rats.

The origin of an endogenous digitalis-like substance in rats was investigated. The tissue content of the substance measured by radio-immunoassay was highest in the pituitary gland, with a decreasing gradient through the hypothalamus, forebrain, cerebellum, brain stem, heart, liver and kidney. Sodium loading decreased the content in the hypothalamus and increased the urinary excretion of the substance. The urinary output of the substance decreased after electrical lesions of the anteroventral third ventricle in the brain. The content increased in the hypothalamus and decreased in the plasma when the axonal flow of neurosecretion was interrupted with intracerebroventricular injections of colchicine. These results suggest that the digitalis-like substance could be produced in the hypothalamus and secreted from the pituitary gland like vasopressin, and that sodium loading increases the turnover of the substance in the hypothalamus.

Animals↗