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Biomedical subjects

T Noshiro

Publications and source records attributed to T Noshiro.

At least 37 records · Page 2Linked to original sources
PubMed1995

Renal dopamine spillover rate using 3H-dopamine radiotracer technique as an index of renal dopaminergic nerve activity.

Renal and total dopamine (DA) spillover rates at rest were measured in 25 conscious rabbits with chronically implanted renal vein catheters. Renal DA spillover rate was calculated from veno-arterial difference in plasma free DA concentrations across the kidney corrected by the fractional extraction of infused 3H-DA. Plasma free DA concentrations were 11.0 +/- 2.7 pg/ml in the artery and 14.3 +/- 3.6 in the renal vein. Renal and total DA spillover rates were 0.51 +/- 0.08, 2.61 +/- 0.30 ng/min, respectively, both of which were significantly (p < 0.001) lower than the respective norepinephrine (NE) spillover rates (renal: 16.3 +/- 1.4, total: 39.6 +/- 1.7). The fractional extraction of 3H-DA across the kidney (55 +/- 3%) and the total DA clearance (285 +/- 31 ml/min) were both significantly (p < 0.05) higher than that of 3H-NE (45 +/- 3) and the total NE clearance (198 +/- 9), respectively. The ratio of renal to the total spillover rate of DA (0.23 +/- 0.05) was significantly (p < 0.05) lower than that of NE (0.41 +/- 0.04). These results demonstrate that DA is released into plasma within the kidney and suggest that the measurement of renal DA spillover rate using 3H-DA radiotracer technique is useful to detect resting renal dopaminergic nerve activity.

Animals↗
PubMed1995

Effect of dexamethasone on plasma free dopamine: dopaminergic modulation in hypertensive patients.

To investigate the peripheral dopaminergic modulation in the pathogenesis of human hypertension, we examined the responses of plasma free dopamine (DA) to dexamethasone (Dx) administration, which is suggested to activate dopaminergic activity. We administered Dx 2 mg intravenously to patients with primary aldosteronism (PA), essential hypertension (EH), and normotensive controls (NT). Plasma free DA was increased significantly in all groups and the responses were more remarkable in PA than in EH and NT. Plasma epinephrine (E) showed a gradual increase while plasma norepinephrine (NE) tended to decrease in all groups. The responses of both plasma DA and E were completely blocked by 250 mg of alpha-methyl-p-tyrosine, a tyrosine hydroxylase (TH) inhibitor, suggesting that Dx may stimulate peripheral dopaminergic activity by increasing catecholamine synthesizing enzyme (probably TH) activities. These data suggest that DA itself plays an inherent role in the sympathoadrenal regulation rather than only as a precursor of NE and that dopaminergic hyperresponses may be involved in the pathophysiology of PA.

Adult↗
PubMed1995

Plasma free dopamine: physiological variability and pathophysiological significance.

Dopamine (DA) is the most abundant catecholamines in human plasma and exists mostly in the sulfo-conjugated form (DA sulfate), a biologically inactive metabolite. The paucity of unconjugated DA (PDA) in plasma throws doubt on its physiological significance. However, PDA, when measured with a highly sensitive radioenzymatic method, showed quite different features from norepinephrine and epinephrine in some types of clinical hypertension, lower in essential hypertension and higher in primary aldosteronism and pheochromocytoma. There was a weak but significant correlation between the values of PDA and DA sulfate measured in the same specimens, but DA sulfate was more susceptible to impaired renal function. Upright posture, high salt diets and an intravenous injection of metoclopramide (MCP, 10 mg), a DA receptor antagonist, induced a slight but significant increase in PDA in normal and hypertensive subjects. An intravenous dexamethasone (2 mg) caused a gradual increase in PDA over 150 min after medication, which was completely blocked by concomitant administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. The responses of PDA to both high salt diets and MCP were blunted in salt-sensitive patients with uncomplicated essential hypertension. The results suggest that DA is not only a precursor of norepinephrine biosynthesis but also plays an inherent role as an active neurotransmitter in the peripheral sympathoadrenal system, and that PDA is a sensitive marker of peripheral dopaminergic activity, which may operate to modulate the cardiovascular and endocrine functions and participate in the pathogenesis of some types of hypertension.

Dexamethasone↗
PubMed1995

Two cases of pheochromocytoma diagnosed histopathologically as mixed neuroendocrine-neural tumor.

We treated two rare cases of pheochromocytoma which were histopathologically diagnosed as mixed neuroendocrine-neural tumor (MNNT): a 35-year-old male patient associated with ganglioneuroblastoma and cutaneous neurofibromatosis and a 42-year-old male patient with ganglioneuroma. Both patients showed typical clinical manifestations of pheochromocytoma without any familial traits. Although each of the diseases has its own entity and clinical features, these tumors are all derived from the neural crest tissues. The tumorigenesis of MNNT is still unknown. Here, a brief review of the recent literature on this subject is discussed.

Adrenal Gland Neoplasms↗
PubMed1995

Clinical evaluation of bevantolol hydrochloride in patients with severe hypertension. The Cooperative Study Group on Bevantolol in Japan.

The clinical efficacy and safety of bevantolol hydrochloride, a newly developed beta-blocker, used in combination with other types of antihypertensive agents, were evaluated in patients with severe hypertension by multicenter open-label trials. A total of 28 patients were studied at 20 medical centers. Four patients (14.3%) were excluded for some reasons, and the remaining 24 patients (22 outpatients and 2 inpatients) were analyzed. Following the initiation of therapy, blood pressure decreased from 181 +/- 15 (SD)/114 +/- 3 mmHg to 170 +/- 17/102 +/- 8 mmHg (p < 0.01) on the 14th day of the therapy and gradually lowered further thereafter. At the end of the trial (8th week), blood pressure was stabilized at the level of 160 +/- 14/96 +/- 10 mmHg. The antihypertensive efficacy rated by the changes in mean blood pressure was 79.2% (19/24). Pulse rate decreased slightly but significantly from 75 +/- 10 beats/min to 70 +/- 7 (p < 0.05) on the 14th day of the therapy and stabilized at the similar level thereafter. As abnormal laboratory data were detected in 3 patients and 1 patient complained of a mild headache, the safety ratio was 83.3% (20/24 patients). When the usefulness was assessed in terms of antihypertensive efficacy and safety profiles, bevantolol hydrochloride was considered useful in 75.0% of the patients studied. In conclusion, bevantolol hydrochloride, used in combination with other classes of antihypertensive agents, appears to be an excellent drug for the management of patients with severe hypertension.

Adrenergic beta-Antagonists↗
PubMed1994

Angiotensin II enhances norepinephrine spillover during sympathetic activation in conscious rabbits.

To investigate the potential modulating influence of angiotensin II (ANG II) on sympathetic activity in response to changes in baroreflex activity, renal and total norepinephrine (NE) spillover rates were examined during sodium nitroprusside (SNP) and phenylephrine (PE) infusions in four groups of conscious rabbits: 1) saline (control); 2) subpressor ANG II (ANG II, 2 ng.kg-1.min-1); 3) enalaprilat (MK-422, 200 micrograms/kg and 3.3 micrograms.kg-1.min-1); and 4) MK plus ANG II (MK+ANG II). Upper plateaus of baroreflex-NE spillover curves for renal and total NE spillover were reduced in the MK group (25 and 81 ng/min) compared with control (38 and 125 ng/min) and MK+ANG II (37 and 155 ng/min). To investigate the interaction of ANG II and sympathetic activity during treadmill exercise, hindlimb NE spillover rate was examined in three groups of rabbits: 1) control, 2) MK, and 3) MK+ANG II. Exercise at 6 and 12 m/min produced similar effort-related hemodynamic responses in the three groups. At maximal exercise, hindlimb NE spillover was reduced in the MK group (29 +/- 3 ng/min) compared with control (62 +/- 17 ng/min, P < 0.05) and MK+ANG II group (51 +/- 10 ng/min). It is concluded that endogenous ANG II enhances sympathetic activity during pharmacological (baroreflex) and physiological stimulation.

Angiotensin II↗
PubMed1993

Enalaprilat restores sensitivity of baroreflex control of renal and total noradrenaline spillover in heart failure rabbit.

1. The acute effect of an angiotensin converting enzyme inhibitor (ACEI), enalaprilat, on baroreflex-mediated changes in renal and total NA spillover rate in conscious rabbits with doxorubicin-induced cardiomyopathic congestive heart failure (CHF) were investigated under resting conditions and in response to changes in arterial pressure induced by sodium nitroprusside and phenylephrine infusions. 2. Six saline-treated (N group) and 11 doxorubicin-treated rabbits (1 mg/kg administered i.v. twice weekly) were studied after 4 and 6 weeks treatment. Five CHF rabbits received saline (C group) and six enalaprilat infusion (ACEI group). 3. After 4 weeks of doxorubicin, mean arterial pressure (MAP)-renal noradrenaline (NA) spillover and MAP-total NA spillover curves did not change during enalaprilat infusion. 4. After 6 weeks, the C group showed blunted MAP-renal NA spillover and MAP-total NA spillover curves. In the ACEI group, however, both curves returned toward those seen in the N group (slope of MAP-renal NA curve: from 0.27 to 1.80 ng/min per mmHg, MAP-total NA curve: from 1.61 to 3.59 ng/min per mmHg). 5. Results of this study indicate that enalaprilat enhances baroreflex control of renal and total NA spillover in rabbits with CHF and further support the view that activation of the renin-angiotensin system contributes significantly to the attenuated baroreflex responses in CHF.

Animals↗
PubMed1991

Effect of angiotensin-converting enzyme inhibition on renal norepinephrine spillover rate and baroreflex responses in conscious rabbits.

1. To evaluate the effects of angiotensin-converting enzyme (ACE) inhibition on sympathetic nerve activity, renal and total norepinephrine (NE) spillover rates were examined under control conditions and during enalaprilat infusion at rest and in response to sodium nitroprusside (SNP)-induced hypotension. 2. Resting renal and total NE spillover rate during enalaprilat infusion were similar to control values. 3. During SNP infusion at 10 micrograms/kg per min, renal NE spillover rate increased by 26% in enalaprilat-treated group and by 39% in controls, in response to falls in mean arterial pressure (MAP) of 25 and 19% respectively. 4. During sympathetic stimulation induced by SNP, total NE spillover rate was significantly increased in both groups, but the 50% (s.e.m. = 12) increase in the enalaprilat-treated group was less (P less than 0.05) than the 97% (s.e.m. = 16) change observed in controls. 5. Enalaprilat treatment resulted in a higher renal to total NE spillover ratio (P less than 0.05). The ratio fell in parallel in both groups during SNP-induced hypotension. 6. This study indicates that the sympathetic nervous system interacts dynamically with the renin-angiotensin system during hypotensive stimulation but this occurs predominantly at sites other than the kidney.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Norepinephrine spillover faithfully reflects renal sympathetic nerve activity in conscious rabbits.

The relationship between directly recorded renal sympathetic nerve activity (RSNA) and simultaneous renal norepinephrine (NE) spillover rate across the kidney at rest and in response to changes in mean arterial pressure (MAP) was examined in six conscious rabbits. Integrated RSNA and renal NE spillover rate at rest were 5.1 +/- 1.1 microV/s and 20.8 +/- 3.0 ng/min, respectively. Sodium nitroprusside infusions at 10 and 20 microgram.kg-1.min-1 significantly increased RSNA by 42 +/- 14 and 84 +/- 14% and renal NE spillover rate 39 +/- 22 and 107 +/- 22% in response to falls in MAP of 15 +/- 2 and 21 +/- 2 mmHg (19 and 27%), respectively. During phenylephrine infusion at 8 micrograms.kg-1.min-1, RSNA and renal NE spillover rate significantly decreased by 65 +/- 14 and 67 +/- 16%, respectively, in response to a 15 +/- 2 mmHg (19%) rise in MAP. There was a highly significant positive correlation between changes in directly recorded RSNA and changes in renal NE spillover rate (r = 0.81, P less than 0.01). The ratio of renal to total NE spillover rate at rest was 0.44 +/- 0.06. This ratio was decreased during both sympathetic stimulation (0.30 +/- 0.04) and inhibition (0.26 +/- 0.06). This study indicates that the measurement of renal NE spillover rate is a useful reliable method for detecting the changes in RSNA and its relative contribution to overall sympathetic nerve activity in response to physiological stimuli in conscious rabbits.

Animals↗
PubMed1990

Functional relationships between platelet alpha 2-adrenoceptors and sympathetic nerve activity in clinical hypertensive states.

Tritiated yohimbine binding was used to estimate platelet membrane alpha 2-adrenoceptor characteristics in normal subjects (n = 12) and patients with essential hypertension (n = 30), primary hyperaldosteronism (n = 10) and phaeochromocytoma (n = 10). There was a 20-fold increase in mean levels of resting norepinephrine and epinephrine in the phaeochromocytoma group. Total binding sites (Bmax) and dissociation constant (Kd) for 3H-yohimbine did not differ significantly among the four groups. Following curative surgery for phaeochromocytoma, plasma catecholamine levels were normalized but the Bmax remained unchanged. Following surgery for primary hyperaldosteronism, levels of plasma norepinephrine rose but Bmax was not changed. In all but the phaeochromocytoma patients, Bmax values correlated positively (r = 0.437, n = 48, P less than 0.01) with resting plasma norepinephrine. A significant negative correlation was observed between the change in plasma norepinephrine in response to postural change and resting Bmax. Treatment for 2-4 weeks with guanabenz or bethanidine induced a parallel fall in both Bmax and plasma norepinephrine. Treatment with reserpine was followed by a comparable fall in plasma norepinephrine, but Bmax values were unchanged. The findings support the view that platelet alpha 2-adrenoceptor density is functionally regulated in parallel with sympathetic nerve activity rather than circulating catecholamine levels, although it is not known which neuronal substance(s) may participate in this regulation.

Adrenal Gland Neoplasms↗
PubMed1989

A sympathetic component of baroreflex function in patients with essential hypertension.

1. The baroreflex-mediated changes in plasma norepinephrine (NE) and heart period (RR interval) to phenylephrine (PE)-evoked pressor and nitroprusside (NP)-evoked depressor stimulations were studied in 19 patients with chronic essential hypertension, 12 with borderline hypertension and in 11 age-matched normal controls. 2. Intravenous infusion of PE at a rate of 0.25-1.0 microgram/kg/min induced dose-related increases in mean arterial pressure (MAP) and in RR interval and a decrease in plasma NE. Similarly, NP infusion at a rate of 0.1-0.4 microgram/kg/min evoked the opposite changes in each variable. The reflex sensitivity was defined as the slope of linear regression between the changes in RR interval and MAP (RR/MAP) and between those in plasma NE (% of the baselines) and MAP (%NE/MAP). 3. Both RR/MAP and %NE/MAP for pressor and depressor stimulations were reduced below values found in normal subjects, in both chronic and borderline hypertensives. 4. The values of %NE/MAP was negatively related to the basal plasma NE during falls in blood pressure (r = -0.401, P less than 0.05). 5. The %NE/MAP may be a useful index of the sympathetic component of baroreflex sensitivity. A decrease in %NE/MAP in hypertensive and borderline hypertensive patients suggests a blunted sensitivity of the sympathetic constrictor reflexes.

Adult↗
PubMed1989

Plasma free dopamine in human hypertension.

The concentration of plasma free dopamine (PDA) is said to be much lower than that of other catecholamines and its physiological significance remains unclear. Our recent studies using a newly developed radioenzymatic method disclosed the fairly distinctive features of PDA in patients with various types of hypertension. PDA was also confirmed as a variable responsive to postural change, dietary sodium loading and dopamine receptor antagonist. The results suggest that PDA could be a sensitive marker to represent the peripheral dopaminergic function, which might play an inherent role as a physiological regulator responsible for the cardiovascular and endocrine system.

Diet↗
PubMed1989

Functional relationship between platelet alpha 2-adrenoceptors and sympathetic nerve activity in man.

Functional relationships between platelet alpha 2-adrenoceptors and sympathetic nerve activity were studied in patients with essential hypertension (n = 23), primary aldosteronism (n = 10), and normal subjects (n = 12). The maximum number of binding sites (Bmax) and the dissociation constant (Kd) of 3H-yohimbine on platelet membranes and resting plasma norepinephrine (NE) were similar among these groups of subjects. In all subjects combined, Bmax values were correlated positively (r = 0.471, p less than 0.01) to resting plasma NE and negatively (r = -0.531, p less than 0.01) to the changes in plasma NE when subjects were moved from lying to standing. A 2-4 week treatment with guanabenz or bethanidine induced a parallel fall of both Bmax and plasma NE, whereas administration of reserpine caused a similar fall of plasma NE but Bmax remained unchanged. Kd values were not changed after any of these treatments. The results support the view that platelet alpha 2-adrenoceptor density is functionally regulated in parallel with sympathetic nerve activity rather than plasma NE per se. This hypothesis seems quite reasonable when it is extended to the presynaptic alpha 2-adrenoceptors; otherwise, the negative feedback function on NE release should be lessened and contradictory to its physiological role.

Adult↗
PubMed1988

[Effects of high sodium diet on dopaminergic mechanism in normal and hypertensive subjects].

To investigate the effects of dietary sodium on the peripheral dopaminergic mechanism, changes of unconjugated plasma dopamine(DA) and its related humoral factors were studied in 8 patients with essential hypertension(EH) and 8 age-matched normal controls(N) while they were receiving ordinary meals (Na, 130-180 mEq daily) followed by higher sodium (250-300 mEq daily) diets for a week. Plasma and urinary DA, norepinephrine(NE) and epinephrine(E) were measured by the highly sensitive COMT-mediated radioenzymatic procedure, which permits an accurate estimation of plasma DA as low as 5-6 pg/ml. Under high sodium diets, blood pressure and heart rate were not changed significantly in N and EH subjects. Urinary NE and E tended to decrease, while urinary DA increased significantly in both groups of subjects (p less than 0.05). There was a significant correlation between urinary sodium and DA (r = 0.590, p less than 0.001), but plasma DA failed to correlate significantly to urinary sodium or DA in all subjects. Plasma NE and E tended to decrease in both N and EH subjects, while plasma DA increased significantly (p less than 0.05) in EH from 7.2 +/- 0.8 pg/ml [mean +/- SEM] to 9.3 +/- 1.0 and slightly in N from 9.1 +/- 1.8 to 11.2 +/- 1.3. Plasma renin activity(PRA) and plasma aldosterone(PAC) were invariably decreased in all subjects, while plasma prolactin(PRL) remained unchanged. A significant correlation was observed between plasma DA and NE under ordinary meals (r = 0.733, p less than 0.01), but this correlation disappeared under high sodium diets. Plasma DA showed an inverse correlation to PAC (r = 0.351, p less than 0.05) under both dietary conditions. Upright posture induced a significant rise (p less than 0.05) in NE, E, DA, PRA and PAC with ordinary meals, but the responses of NE and PAC were apparently attenuated with high sodium diets. An intravenous injection of metoclopramide (MCP, 10 mg), a DA receptor antagonist, provoked a slight rise in plasma NE and DA with ordinary meals, of which responses were further enhanced with high sodium diets. MCP induced a definite rise in PAC and PRL in all subjects under both dietary conditions (p less than 0.01), while plasma E and PRA remained unchanged after MCP challenge. The results lend support to the view that unconjugated plasma DA could be a useful marker of peripheral dopaminergic activity, which might be a physiological regulator responsible for the suppression of aldosterone secretion and sympathetic nerve activity observed during high sodium intake.

Adult↗