Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 649 records · Page 36Linked to original sources

PubMed1987

Slow IPSP and the noradrenaline-induced inhibition of the cat sympathetic preganglionic neuron in vitro.

Focal electrical stimulation of the slice of the cat thoracic cord evoked in sympathetic preganglionic neurons a slow inhibitory postsynaptic potential (IPSP) associated with decreased neuronal input resistance. The slow IPSP decreased in amplitude with membrane hyperpolarization and reversed at about -90 mV. It increased in amplitude in low potassium and decreased in high potassium. Noradrenaline (NA) at doses of 10-50 microM caused in some of these cells a hyperpolarization with properties similar to those of the slow IPSP. Both the slow IPSP and the NA-evoked hyperpolarization were abolished by yohimbine, but not by prazosin or propranolol. These data suggest that both responses are due to an increase in potassium conductance and that NA may be the mediator of the slow IPSP evoked by focal stimulation.

Action Potentials↗

PubMed1987

Slow EPSP and the depolarizing action of noradrenaline on sympathetic preganglionic neurons.

Intracellular recordings were made from sympathetic preganglionic neurons of the lateral horn in slices of cat thoracic cord maintained in vitro. Focal electrical stimulation of the slice evoked, in addition to the already described fast EPSPs, EPSPs of several seconds duration. The slow EPSPs, like the fast EPSPs, were graded with stimulus intensity and were abolished by TTX or low Ca and high Mg superfusion. The slow EPSP decreased in amplitude with membrane hyperpolarization and was nullified at -90 mV but did not reverse with further hyperpolarization. The slow EPSP was abolished by phentolamine or prazosin but not by yohimbine. Noradrenaline NA, 10-50 microM) caused in 30% of neurons a TTX-resistant depolarization. The NA-evoked depolarization had the same characteristics as the slow EPSP with respect to sensitivity to membrane potential and to adrenergic blockers. These results suggest that NA, acting on an alpha 1-receptor, may be the mediator of the slow EPSP evoked in this neuron by focal stimulation.

Action Potentials↗

PubMed1987

[The source and significance of increased urinary dopamine excretion during sodium loading in rats].

To investigate the source and physiological significance of urinary free dopamine (f-DA) in high sodium diet (8% NaCl) loading, the effects of renal denervation and administration of carbidopa, an inhibitor of peripheral dopa decarboxylase, on urinary f-DA excretion were studied in male Wistar rats. Carbidopa was orally administered in a dose of 20mg/kg every 12h. To ascertain the extent of denervation, kidney norepinephrine was measured. Catecholamines were assayed by HPLC with electrochemical detection. Urinary f-DA and sodium excretion were significantly increased in response to the added NaCl. There were few effects of renal denervation on urinary excretion of f-DA and sodium in high sodium diet loading, whereas carbidopa caused a significant fall not only in urinary f-DA excretion but also in urinary sodium excretion. A highly significant correlation was also found between sodium excretion and f-DA excretion on the 5th day of carbidopa treatment. The data indicates that urinary f-DA in a high sodium diet is mainly derived from the renal tubular cells but not from renal nerves and that f-DA may be an important natriuretic hormone.

Administration, Oral↗

PubMed1987

Role of renal nerves and dopamine on prostaglandin E release from the kidney of rats.

The aim of the study is to investigate the role of renal nerves and dopamine (DA) on urinary excretion of prostaglandin E (PGE) released from kidney with or without salt loading in rats. After excessive intake of high Na, urinary excretions of PGE and DA enhanced as compared with those of basal Na. In rats with renal denervation, urinary excretion of PGE and norepinephrine decreased in salt loading, and urinary Na excretion increased. Urinary PGE excretion was also enhanced by treatment of bromocriptine accompanying with augmented natriuresis. Urinary PGE excretion was suppressed by treatment of carbidopa, which also suppressed the urinary excretion of DA. These results suggest that the renal adrenergic nerve and tubular DA in kidney play an important role on the release of PGE and that these mechanisms in PGE release from kidney augment in salt loading.

Animals↗

PubMed1987

A transient outward rectification in the cat sympathetic preganglionic neuron.

Intracellular recordings were made from sympathetic preganglionic neurons of the intermediolateral nucleus, in the slice of the T3 segment of the cat spinal cord. Depolarization to -60 mV from membrane potentials more negative than -75 to -80 mV caused a transient outward rectification which decayed in 0.5-2.0s. The rectification was sensitive to changes in K concentration, was abolished by 4AP (2 mM), and was unaffected by low Ca (0.25 mM), Co (2 mM), Ba (1 mM), TEA (20 mM) or intracellular Cs. These properties suggest that the rectification is due to a transient K-current similar to the A-current described in other neurons.

Animals↗

PubMed1987

Study of the growth factors for the mammary gland: epidermal growth factor and mesenchyme-derived growth factor.

The physiological importance of EGF in the development of the mouse mammary gland during pregnancy and in spontaneous mammary tumorigenesis has been documented by a series of experimental results presented herein. In our study, we have taken a variety of experimental approaches including radioimmunoassay of EGF in the submandibular gland and plasma, mammary gland organ/cell culture, EGF receptor assay, sialoadenectomy and treatment with EGF and EGF antibodies to assess the role of EGF in the mammary gland. In particular, studies employing sialoadenectomy and EGF replacement have provided valuable information concerning the function of EGF in the body. These studies are possible in the mouse system because the submandibular gland serves as a major source of circulating EGF and also because purified mouse EGF is available commercially. Our work on the biological, endocrinological, and physiological aspects of EGF in normal and neoplastic growth of the mammary gland should be useful for the study of the regulation of mammary gland growth at the molecular level as well as for clinical investigations of mammary tumors. Finally, our findings of a mammary growth factor in embryonic mesenchymal cultures suggest the possible involvement of paracrine growth factor(s) in mammary cell growth. Further progress in this area is needed for better understanding of the complex process of mammary gland growth and development.

Animals↗

PubMed1987

Significance of IgA deposits on the glomerular capillary walls in IgA nephropathy.

Based on immunofluorescence findings, 232 patients with IgA nephropathy were classified into two groups; one consisted of 88 patients (38%) with IgA deposits in the glomerular capillary walls together with the mesangial deposits (capillary type), and the other consisted of 144 patients (62%) with deposits confined to the mesangium (mesangial type). Electron microscopic findings revealed dense deposits on the capillary walls (subepithelial, 50%; intramembranous, 65%; and subendothelial, 24%) in 37 of 46 patients with capillary type and six of 47 with mesangial type (P less than .001). Crescent formation observed in greater than or equal to 10% of glomeruli was more frequently found in patients with the capillary type (30/88, 34%) than those with the mesangial type (9/144, 6%) (P less than .01), especially higher in those with subepithelial deposits (15/26, 57%). The capillary type patients showed heavier proteinuria (1.7 +/- 0.2 g/d) than the mesangial type patients (0.6 +/- 0.1 g/d) (P less than .05). Thirteen of the 14 patients in an acute exacerbation phase, manifested by an abrupt increase in urinary protein and development of macroscopic hematuria, showed capillary type IgA deposits. The ratio of patients with normal renal function in the fifth year after apparent onset was lower in the capillary type (74.0%) than in the mesangial type patients (96.9%) (P less than .05). These findings suggest that capillary IgA deposition is closely related to clinical and histologic activities of IgA nephropathy and is considered to be an important factor responsible for the progression of the disease, possibly through crescent formation.

Acute Disease↗

PubMed1987

Centrally induced vasopressor responses to ouabain in DOCA-salt hypertensive rats.

To investigate the effect of inhibition of cerebral Na+, K+-ATPase on cardiovascular regulation ouabain was injected into the lateral ventricle or the posterior hypothalamus in either conscious or urethane anaesthetised, deoxycorticosterone-salt hypertensive (DOCA) and sham operated (sham) rats. Ouabain injected intracerebroventricularly produced dose dependent vasopressor responses and tachycardia in the conscious rat; the magnitude of the pressor response was consistently larger in DOCA than in sham rats. In anaesthetised rats the pressor responses were accompanied by corresponding increases in abdominal sympathetic nerve activity. Thus the magnitude of the pressor responses, tachycardia, and the increases in nerve activity was again significantly greater in DOCA than in sham rats. Intrahypothalamic injections of ouabain produced pressor responses that were accompanied by consistent increases in both heart rate and abdominal sympathetic nerve activity in anaesthetised rats. In contrast to the intracerebroventricular injections the percentage increases from baseline blood pressure were significantly greater in sham than in DOCA rats at 5 min after injection. These results indicate that the centrally induced vasopressor response to ouabain, via the periventricular or bulbospinal system or both, is increased in DOCA-salt hypertensive rats whereas the pressor mechanism via the posterior hypothalamus is suppressed in DOCA rats.

Action Potentials↗

PubMed1987

Sympatholytic effects of the intravenously injected alpha 1-adrenergic blocker, bunazosin, in anaesthetized rats.

Cardiovascular regulation during alpha 1-adrenergic blocker-induced vasodepression was investigated in urethane-anaesthetized rats. Intravenous (i.v.) injections of bunazosin, an alpha 1-blocker, elicited depressor responses which were accompanied by corresponding decreases in both heart rate and abdominal sympathetic discharge, dose-dependently. Those responses were not affected by the bilateral sino-aortic de-afferentation. Assuming that the site of action is in the central nervous system, bunazosin was injected intracerebroventricularly (i.c.v.). It produced hypotension accompanied by decreases in heart rate and abdominal sympathetic nerve activity. The magnitude of the responses was greater when bunazosin was injected i.c.v. than when injected i.v. Since these results indicated that the central alpha 1-adrenergic receptors mediate vasopressor responses, the effects of i.c.v. injections of an alpha 1-agonist, phenylephrine was explored. It elicited vasopressor responses accompanied by corresponding increases in heart rate and abdominal sympathetic nerve activity. Furthermore, i.c.v. pretreatment with bunazosin abolished the vasopressor responses to i.c.v. injections of phenylephrine. These results indicate that central alpha 1-adrenergic receptors mediate vasopressor responses and that i.v. injections of alpha 1-blockers affect the central alpha 1-receptors, to produce a decrease in sympathetic nerve activity. Consequently, alpha 1-adrenergic blockers decrease blood pressure not only by peripheral vasodilation but also by inhibition of the sympathetic outflow in rats.

Adrenergic alpha-Antagonists↗

PubMed1987

The venous skin graft method for repairing skin defects of the fingers.

A venous skin graft for the treatment of skin defects in a finger is described. This procedure involves taking a flap from the forearm together with the subcutaneous vein and anastomosing both ends of this vein to the digital artery and vein, respectively. Thirteen difficult finger wounds were resurfaced with such a venous skin graft. The sizes of the flaps ranged from 1.3 X 3.0 cm to 2 X 5 cm. The lengths of the veins taken were from 6 to 12 cm. Subcutaneous fat is thin, and there is good elasticity in the grafted flap.

Adult↗

PubMed1987

Effects of hypoxia on rat hippocampal neurones in vitro.

1. The effects of hypoxia on the rat hippocampal CA1 neurones in tissue slices of the rat brain were studied in vitro by intracellular recording. 2. In response to superfusion of a hypoxic medium equilibrated with 95% N2-5% CO2, a majority of the neurones showed a hyperpolarization of 5-15 mV in amplitude and 4-12 min in duration. The hyperpolarization was, in turn, followed by a slow depolarization which within 20 min of hypoxic exposure reached a plateau level of about 25 mV above the pre-hypoxic resting potential. Both the initial hyperpolarization and subsequent depolarization were associated with a reduction in membrane resistance. 3. The hyperpolarization reversed in polarity at a membrane potential of -83 mV. There was an almost linear relationship between amplitude of the hyperpolarization and membrane potential. The hyperpolarization was markedly enhanced in potassium-free media and was depressed in high-potassium solutions. 4. The hyperpolarization was not significantly affected by low-chloride or low-sodium medium or by solution containing tetraethylammonium (10 mM), 4-aminopyridine (1.5 mM) or caesium (3 mM). Moreover, intracellular injection of ethyleneglycol-bis-(beta-aminoethylether)N,N-tetraacetic acid (EGTA) did not alter the hyperpolarization. On the other hand, barium (0.5 mM)-containing medium reduced the amplitude of the hyperpolarization by 20-40%. 5. Superfusion of ouabain (5-7 microM)-containing medium in normoxic conditions produced hyperpolarizing and depolarizing responses similar to those elicited by hypoxic exposure. The slow depolarization was also mimicked by elevation of the extracellular potassium concentration to 10-20 mM. 6. Evoked i.p.s.p.s were abolished within 4 min of hypoxic exposure while evoked e.p.s.p.s were maintained for about 20 min of hypoxic superfusion. Soma spikes of the neurones elicited by a depolarizing pulse were also well preserved. Their threshold was, however, raised, concomitant with a decrease in the peak amplitude. 7. When the slice was reoxygenated after 20-40 min of hypoxic exposure, the neurones immediately began to repolarize and showed a transient hyperpolarization of 5-10 mV in amplitude and 1-2 min in duration. The membrane potential, input resistance and action potential returned to the pre-hypoxic levels after 15-20 min of reoxygenation. The amplitude of the reoxygenation-induced hyperpolarization was not significantly changed when the membrane was hyperpolarized or depolarized. The hyperpolarization was eliminated by potassium-free medium or solution containing ouabain (1 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1987

Noradrenaline-induced afterdepolarization in cat sympathetic preganglionic neurons in vitro.

Sympathetic preganglionic neurons of the intermediolateral nucleus were identified by antidromic stimulation in the slice of the T2 or T3 segment of the cat spinal cord. In normal Krebs solution, the action potential of these neurons had a shoulder on the repolarization phase and was followed by a long-lasting afterhyperpolarization (AHP). The AHP had a fast and a slow component. Superfusion of the slice with noradrenaline (NA), 10-50 microM, resulted in depression of the shoulder on the repolarization phase of the action potential, in the appearance of an afterdepolarization (ADP), which was absent in control conditions, and in depression of the slow component of the AHP. These effects were present whether the membrane potential of the sympathetic preganglionic neurons was decreased, increased, or not changed by NA. A typical ADP had time to peak of 50 ms and decay time of 200-500 ms; the amplitude was variable and large ADPs could be suprathreshold, causing repetitive firing. The amplitude and duration of the ADP increased with NA concentration. The appearance of the ADP seemed to be independent of the depressant effect of NA on the slow AHP. The ADP was associated with a decrease in neuron input resistance and was voltage dependent, being depressed in nonlinear fashion by membrane hyperpolarization. The ADP decreased in amplitude or disappeared within a range of membrane potentials from -70 to -90 mV. The ADP was reversibly suppressed by the Ca-channel blocker cobalt (2 mM), by low Ca Krebs (0.25 mM), and by iontophoretic injection of ethyleneglycol-bis(B-aminoethyl-ether)-N,N'-tetraacetic acid into the cell. Increasing Ca concentration from 2.5 to 10.0 mM had no effect. The ADP was unaffected by tetrodotoxin, at a concentration blocking the Na spike, but was suppressed in Na-free medium, even when the Ca spike was prolonged by tetraethylammonium 20 mM. Changes in external K concentration from 3.6 to 2.5 or 10.0 mM did not change the ADP. Increasing intracellular Cl concentration or decreasing extracellular Cl concentration had no effect on the ADP. It is concluded that the ADP, evoked by NA, is due to an increase in membrane conductance involving Na and Ca ions, possibly a Ca-activated Na conductance. The ADP provides a mechanism with which NA may modulate sympathetic preganglionic neuron responsiveness to excitatory synaptic inputs.

Action Potentials↗

PubMed1987

Afterdepolarization mechanism in the in vitro, cesium-loaded, sympathetic preganglionic neuron of the cat.

Intracellular recordings were performed in Cs-loaded sympathetic preganglionic neurons (SPNs) of the intermediolateral nucleus, identified by antidromic stimulation, in the slice of the T2 or T3 segment of the cat spinal cord. Loading the neurons with Cs resulted in broadening of the action potential, depression of the fast component of the afterhyperpolarization (AHP), and appearance of an afterdepolarization (ADP). A typical ADP in a Cs-loaded neuron had time to peak of 45-110 ms, half-decay time of 70-250 ms, and amplitude of 2-10 mV at membrane potentials between -60 and -70 mV and at a Ca and K concentration of 2.5 and 3.6 mM, respectively, in the superfusion medium. The ADP was associated with a decrease in neuron input resistance and increased in magnitude with hyperpolarization of the cell membrane. The relation between peak ADP amplitude and membrane potential was linear within the range of membrane potentials from -60 to -100 mV. The ADP was reversibly suppressed by the Ca-channel blocker cobalt (2 mM) or by low Ca Krebs solution (0.25 mM). Superfusion with BaCl2 (1.0 mM) or tetraethylammonium (TEA) (10-20 mM) caused an increase in amplitude of the ADP and an increase in action potential duration. Hyperpolarizing pulses, delivered during the course of the spike shoulder, resulted in a decrease of spike duration and ADP amplitude. The ADP was not affected by tetrodotoxin, at a dose blocking the Na-spike, and was enhanced, in association with an increase in action potential duration, when NaCl in the Krebs solution was replaced with choline chloride. Increasing intracellular Cl concentration or decreasing extracellular Cl concentration had no effect on the ADP. Changes in external K concentration from 3.6 to 10 or 0.36 mM increased and decreased, respectively, the amplitude of the ADP. In the absence of Cs, and ADP, with similar time course to that recorded in Cs-loaded SPNs, was recorded when CaCl2 was replaced by BaCl or NaCl was replaced by TEAC1. It is concluded that the SPN afterpotential includes a Ca-dependent inward current, in addition to the already described fast and slow outward K currents of the AHP.

Action Potentials↗

PubMed1987

Evidence for a digitalis-like substance in the hypothalamopituitary axis in rats: implications in the central cardiovascular regulation associated with an excess intake of sodium.

The origin and the physiological role of an endogenous digitalis-like substance were investigated by measuring both the digoxin-like substance by a digoxin radioimmunoassay (RIA) and the inhibitory activity on the ouabain sensitive Na+,K+-ATPase in rats. The digitalis-like substance was in high concentration in the pituitary, and in decreasing concentration in the hypothalamus, adrenal and the other organs as measured by RIA using an antibody raised from a goat. However, the adrenal showed the highest content of digitalis-like substance as measured by the antibody raised from a rabbit. The plasma level markedly decreased during a 2-week sodium-loading, and the adrenal content decreased markedly on hypophysectomy as measured with the rabbit-antibody. Therefore, the substance measured with the rabbit-antibody must be one of ACTH-dependent adrenal steroids. The inhibitory activity on the Na+,K+-ATPase was high in the pituitary gland, and was decreased in order of the adrenal, hypothalamus and other organs. The 2-week sodium-loading increased both the content in the pituitary gland and the output in the urine, and decreased the hypothalamic content. Immunohistochemical staining of the hypothalamus with the antibody revealed that the immunoreactivity is restricted to the neurons of the paraventricular nucleus, supraoptic nucleus, magnocellular accessory nuclei and extended their fibers reaching to the inner layer of the median eminence. To determine the role of the substance in the brain, the crude extract dissolved in artificial cerebrospinal fluid was injected into the lateral ventricle; vasopressor responses, tachycardia and hyperactivity of the splanchnic nerve lasting for more than 30 min were recorded, which resembled the responses to ouabain injected similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Pathophysiological role of dopamine on the development of hypertension in rats.

The aim of the study is to investigate the pathophysiological role of dopamine (DA) in the development of hypertension in DOCA-salt hypertensive rats and spontaneously hypertensive rats (SHRs). The augmentation of dopaminergic activity by chronic administration of bromocriptine, a DA agonist, suppressed the increase of blood pressure in DOCA-salt hypertensive rats. In contrast, suppression of dopaminergic activity by chronic administration of carbidopa, an inhibitor of dopa decarboxylase, accelerated the development of hypertension in SHRs, and this acceleration was also increased by salt loading. Increased urinary excretion of norepinephrine (NE) by DOCA-salt treatment was suppressed by the treatment of bromocriptine. In contrast, administration of carbidopa and salt loading in SHRs resulted in an increase in renal NE content and in urinary NE and epinephrine (E) excretion and a decrease in urinary sodium excretion. These results suggest that dopaminergic activity participate in the development of hypertension and decreased dopaminergic activity accelerates the development of hypertension in hypertensive rats mainly through the enhancement of peripheral sympathetic nerve activity.

Animals↗

PubMed1987

Microbiological monitoring in inbred mouse foundation stocks in Japan.

Microbiological monitoring on 128 inbred mouse foundation stocks consisted of common 10 inbred strains and inbred strains originated from outbred dd mice was performed by cooperation of 24 organizations. A total of 881 mice were divided into 647 conventional animals from 95 colonies and 234 barrier-sustained animals from 33 colonies. Three viral, one mycoplasmal, 6 bacterial, one fungal and 3 parasitic agents selected as monitoring microbes according to the proposed selection standards. Among conventional colonies, 84.2% were positive for at least one agent. The highest detection rate was 44.2% for S. obvelata, followed by P. pneumotropica and S. muris, P. aeruginosa, G. muris, Sendai virus, M. pulmonis, MHV and E. coli O115a, c: K (B). Of these agents, only one microbe, P. aeruginosa, was detected in barrier-sustained colonies (36.4%), thus the efficacy of barrier system for the microbiological quality control of the inbred mouse foundation stocks was actually demonstrated. The positive rates of MHV (6.3%) and Sendai v. (16.8%) were significantly low compared with those in experimental mouse colonies. Positivity for parasites was rather high and they were infested together with other pathogens in many cases. Thus parasites including G. muris, S. muris and S. obvelata were regarded as useful indicators to see microbiological contaminations in conventional mice. There observed no strain difference in susceptibility to pathogens except for C57BL/6 and AKR mice which seemed to be high antibody responders to MHV.

Animals↗

PubMed1987

Involvement of dopamine in development of hypertension in spontaneously hypertensive rat: effect of carbidopa, inhibitor of peripheral dopa decarboxylase.

The demonstration of acceleration of hypertension was investigated in spontaneously hypertensive rats (SHR) treated with carbidopa, inhibitor of peripheral dopa decarboxylase. Oral administration of carbidopa to young SHR for 4 weeks accelerated significantly (P less than 0.05) development of hypertension as compared to SHR treated with vehicle. Urinary excretion of dopamine (DA) (P less than 0.01) and renal content of DA (P less than 0.02) were significantly decreased by carbidopa treatment. Urinary excretion of sodium (P less than 0.05) was significantly decreased and renal content of norepinephrine (NE) (P less than 0.01) was significantly increased by carbidopa. Urinary excretion of NE and epinephrine (E) did not change during the experimental period. Negative correlation between systolic blood pressure and urinary excretion of sodium (P less than 0.05) or dopamine (P less than 0.01) and positive correlation between systolic blood pressure and renal content of NE (P less than 0.05) were significantly observed in both groups of SHR treated with carbidopa and with vehicle for 4 weeks. These results suggest that decreased DA biosynthesis in peripheral tissues accelerates development of hypertension mediated by decrease of natriuresis and enhanced release of NE in the kidneys of SHR. DA plays an important role in regulation of blood pressure, and reduced dopaminergic mechanisms enhance blood pressure in SHR.

Animals↗

PubMed1987

Effect of decreased dopamine synthesis on the development of hypertension induced by salt loading in spontaneously hypertensive rats.

To clarify role of dopamine in the development of hypertension, the effect of a dopamine synthesis inhibitor on blood pressure and urinary output of catecholamines was investigated in spontaneously hypertensive rats (SHR) fed with high sodium diet. Rats were orally given carbidopa, an inhibitor of peripheral DOPA decarboxylase, or the vehicle for 4 weeks. Carbidopa administration accelerated significantly the development of hypertension as compared to the control SHRs with the vehicle. Carbidopa administration resulted in a significant decrease of urinary excreted sodium, urinary dopamine and renal content of dopamine. Conversely, carbidopa administration resulted in a significant increase of urinary excreted norepinephrine, urinary epinephrine and renal content of norepinephrine as compared with control SHRs. These results suggest that decreased dopamine synthesis in kidneys and probably other peripheral tissue accelerates the development of hypertension, mediated by a decrease of natriuresis and an enhancement of sympatho-adrenomedullary activity. Dopamine plays an important role in its protective action against the development of hypertension enhanced by salt loading, and decreased dopaminergic mechanisms accelerated hypertension in SHR.

Animals↗