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S Shigetomi

Publications and source records attributed to S Shigetomi.

17 recordsLinked to original sources
PubMed1992

Defective dopamine generation from dihydroxyphenylalanine in stable essential hypertensive patients.

We studied the metabolic pathways of dihydroxyphenylalanine (DOPA) and dopamine as well as the cardiovascular and renal responses to a single administration of DOPA (500 mg orally) in stable essential hypertension. We found that after DOPA, stable hypertensive patients compared with controls showed more blood pressure decrease without reflex tachycardia, had lower creatinine clearance but a higher fractional excretion of sodium, and had lower plasma renin activity at the height of DOPA action. Hypertensive patients also showed increased plasma DOPA, the ratio of plasma DOPA to dopamine, and the sum of plasma DOPA and 3-O-methyl-DOPA, as well as increased urinary 3-O-methyl-DOPA and the plasma and urine dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid. Finally, despite an augmented post-DOPA glomerular load of DOPA, the predominant source of urinary dopamine, the excretion rates of dopamine and its metabolites remained comparable in hypertensive patients to those in control subjects. These data suggest that, in stable hypertensive patients, exogenous DOPA is to a lesser degree decarboxylated to dopamine, which is more rapidly metabolized intraneuronally. Contrasting with this finding are the hyperdopaminergic features, such as hypernatriuresis with renin suppression and excessive blood pressure decline in the absence of reflex tachycardia. They may be due to an upregulation of renal, vascular, and brain dopaminergic receptors secondary to a preexisting dopaminergic deficiency in stable essential hypertension.

Administration, Oral↗
PubMed1991

Dopaminergic abnormalities in borderline essential hypertensive patients.

To explore whether an altered metabolic pathway of dihydroxyphenylalanine (DOPA) may be related to some previously observed dopamine abnormalities in borderline hypertension, we measured basal and DOPA-induced (500 mg orally) changes in blood pressure and pulse rate as well as in three hourly plasma and urine samples. We found that borderline hypertensive patients compared with controls 1) showed a higher baseline urinary excretion of methoxytyramine, a marker of exocytotic dopamine release, with a greater DOPA-induced decrease of systolic blood pressure without reflex tachycardia; 2) had in response to DOPA a blunted plasma DOPA and free dopamine increase but an accentuated plasma dopamine sulfate and urinary DOPAC excretion; and 3) eliminated comparable quantities of dopamine in urine despite a lower rise in the glomerular DOPA load. Furthermore, although DOPA elicited natriuresis in both groups, its effect was greater in borderline hypertensive patients, who lacked the urinary sodium correlation with urinary dopamine excretion seen in control subjects. These data are compatible with increased basal exocytotic dopamine release and accelerated neuronal and renal (extraneuronal) dopamine generation from administered DOPA in borderline hypertension. The DOPA-induced hypernatriuresis exceeding augmented dopamine in borderline hypertensive patients, contrasting with the urinary sodium and dopamine correlation in control subjects, suggests that DOPA induced an additional natriuresis in borderline hypertensive patients by a decrease in renal sympathetic tone because of its central inhibition of sympathetic outflow, which also may account for the absence of reflex tachycardia.

Adult↗
PubMed1991

A case of glomerulocystic kidney disease associated with hypothyroidism in man.

Glomerulocystic kidney (GCK), a rare disease mostly seen in infants and small children, is characterized by dilatation of Bowman's space. We report about a 32-year-old Japanese male with GCK. Although radiologic studies including computed tomography of the kidneys failed to show cysts in the corticomedullary regions, renal biopsy specimens revealed diffuse glomerular cystic lesions. Extrarenal malformations were not determined, but the patient was found to have hypothyroidism presumably due to a functional disorder of the hypothalamus (tertiary hypothyroidism). This is probably the fifth documented case of the disease in an adult. To our best knowledge, the association with hypothyroidism is rare. Although its pathogenic relevance to GCK is unknown, the endocrine dysfunction seems to have occurred as part of the extrarenal conditions of GCK, which calls further attention to this entity.

Adult↗
PubMed1990

[The significance of cGMP and dopamine receptor on the natriuretic and hypotensive activities of synthetic atrial natriuretic polypeptide in essential hypertension].

This study was undertaken to clarify the role of dopamine receptor (DA2) on the effects of atrial natriuretic polypeptide(ANP) on blood pressure, plasma and urinary cyclic GMP, and urinary sodium excretion, alpha-human ANP (alpha-hANP) was intravenously administrated to 7 normal subjects and 14 patients with essential hypertension as follows: first a dose of 0.01 micrograms/kg/min for 30 minutes, and then 0.03 micrograms/kg/min with or without metoclopramide(MC) for 30 minutes. After the infusion of the 0.03 micrograms/kg/min dose of alpha-hANP, systolic blood pressure fell from 115 +/- 17 mmHg to 109 +/- 15 mmHg in normal subjects, and fell significantly from 163 +/- 33 mmHg to 145 +/- 26 mmHg in patients with essential hypertension. Diastolic blood pressure fell from 101 +/- 14 mmHg to 92 +/- 7 mmHg in patients with essential hypertension but did not change in normal subjects. A dose of 0.03 micrograms/kg/min of alpha-hANP led to a threefold rise in urine volume and twofold rise in urinary sodium excretion in normal subjects, and a fivefold rise in urine volume and fourfold rise in urinary sodium excretion in patients with essential hypertension. However, there was no relationship between the hypotensive and natriuretic effects of alpha-hANP in either normal subjects or patients with essential hypertensions. The infusion of a 0.03 micrograms/kg/min dose of alpha-hANP increased plasma cyclic GMP concentration from 4.1 +/- 2.1 pmol/ml to 34.3 +/- 25.Opmol/ml in normal subjects and from 4.5 +/- 2.6 pmol/ml to 20.3 +/- 7.4 pmol/ml in patients with essential hypertension. The rise in plasma cyclic GMP by alpha-hANP was suppressed by MC both in normal subjects and patients with essential hypertension. Urinary cyclic GMP excretion also increased during the infusion of alpha-hANP, but this effect was not suppressed by MC. Furthermore, plasma aldosterone concentration (PAC), which was depressed by alpha-hANP in normal subjects and patients with essential hypertension, was increased by MC. These results suggest that the hypotensive effect of alpha-hANP may depend not only on the natriuretic effect, but also on vasodilatation, the inhibition of aldosterone production or the suppression of the sympathoadrenomedullary system. Cyclic GMP may be produced through the DA2 receptor in vascular tissue but not in the kidney.

Aldosterone↗
PubMed1989

[The role of Na+-K+ ATPase activity on blood pressure regulation and sodium metabolism in DOCA-treated rats].

In this study, we attempt to clarify the role of sodium-potassium adenosine 5'-triphosphatase (N+-K+ ATPase) on the regulation of systemic blood pressure and renal sodium metabolism. Male Wistar rats (n=20) were divided into four groups: 1) controls (n=5), 2) sodium loading rats (NaCl group, n=5), 3) deoxycorticosterone (DOCA group, n=5) injected rats with intact kidneys (DOCA group, n=5), 4) DOCA and ouabain-injected rats with intact kidneys (ouabain groups) and raised for six weeks. The changes in urine volume and urinary sodium were determined, and urinary excretions of norepinephrine (NE), epinephrine (E) and dopamine were measured in week six. Then blood samples were obtained from the inferior vena cava, and plasma cyclic AMP (cAMP) and cyclic GMP (cGMP) concentration were measured. At the time of sacrifice, systolic blood pressure of the ouabain group (157.3 +/- 24.8 mmHg) was significantly higher than the control group (124.5 +/- 6.9 mmHg) (p less than 0.05), but no significant differences were observed between the control group, NaCl group (123.7 +/- 7.0 mmHg), and DOCA group (128.1 +/- 4.5 mmHg). Urine volume and sodium excretion in the NaCl, DOCA and ouabain groups all increased, but the natriuretic response in the NaCl group was smaller than in either the DOCA and ouabain groups. Urinary NE in the NaCl, DOCA and ouabain groups was 1396 +/- 1025 ng/day, 640 +/- 351 ng/day, 607 +/- 177 ng/day, respectively, and NE excretions in these groups were higher than in the control group (138 +/- 104 ng/day). Urinary E in the NaCl group was higher than in the control group, but there were no significant differences among the control, DOCA and ouabain groups. Urinary dopamine in the NaCl (5723 +/- 2028 ng/day), DOCA (7661 +/- 5992 ng/day) and ouabain (4077 +/- 1984 ng/day) groups was higher than in the control group (2081 +/- 483 ng/day). Plasma cAMP in the DOCA and ouabain groups was slightly higher than in the control group, while no significant differences in plasma cAMP between the control and NaCl groups were observed. Plasma cGMP in the DOCA group was slightly higher than in either of the other three groups. These results suggest that Na+-K+ ATPase may play an important role in the maintenance of blood pressure through sodium efflux and that ouabain, Na+-K+ ATPase inhibitor, may change the renal sodium excretion and vascular responsiveness to endogenous pressor substances, leading to higher blood pressure after the administration of sodium and mineralocorticoid.

Animals↗
PubMed1989

[Increased plasma and urinary Na+-K+ ATPase inhibitory activity and elevated blood pressure in metoclopramide-treated rats].

Our recent studies demonstrated that dopaminergic receptor may play an important role in controlling blood pressure and renal sodium handling. This study was designed to investigate whether endogenous Na+-K+ ATPase inhibitors are related to changes in blood pressure and sodium balance, caused by the administration of metoclopramide (MC), a dopamine (D2) receptor antagonist, and sodium loading. Young male Wistar rats (250 approximately 300 g) were raised under three different conditions, control (control group), 1% NaCl loading (NaCl group) and 1% NaCl plus 1.5 mg/kg/day of metoclopramide (MC group) for 7 days. Systolic blood pressure (SBP), urinary and plasma Na+-K+ ATPase inhibitory activity (ATPI), urinary sodium, potassium and catecholamine excretions were measured. SBP in the MC group elevated from 116 +/- 2 mmHg to 134 +/- 4 mmHg, but there were no changes in SBP in the control and NaCl groups. Urine volume and urinary sodium excretion significantly increased in not only the NaCl group but also in the MC group. Plasma ATPI in both the NaCl and MC groups was higher than in the control group (p less than 0.001), and the level of ATPI in the MC group was significantly higher than in the NaCl group (p less than 0.05). Urinary ATPI in the control group was not detected after 7 days, but that in the NaCl and MC groups was clearly increased. The excretions of urinary catecholamines remained unchanged in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[Effects of dopamine and synthetic atrial natriuretic polypeptide on the release of norepinephrine and epinephrine from the adrenal medulla of rats].

We evaluated the effects of dopamine (DA) and synthetic atrial natriuretic polypeptide (ANP) on the release of catecholamines (CA) from the adrenal medulla. Adrenal glands of male Wistar rats were superfused with Ringer's solution saturated with 95%, O2, 5% CO2 by the use of a continuous flow incubation system, and norepinephrine (NE) and epinephrine (E) concentrations in the perfusate were continuously measured by high pressure liquid chromatography with fluorescent reaction. And the effects of DA and ANP on the CA release were evaluated. Next the effects of metoclopramide (MC), dopamine (D2) antagonist, and glucagon were added in the Ringer's solution, and the changes of NE and E in the perfusate were determined. Basal secretion of NE and E were 0.02-0.04 ng/mg.wet weight/min and 0.05-0.1 ng/mg.wet weight/min, respectively. DA remarkably decreased both NE and E release, and the suppressive effect was dependent on DA concentration in the perfusate. MC clearly raised NE and E release as well as glucagon. The increasing effect of MC was perfectly suppressed by 10(-4) M of DA. But the effect of glucagon was not blocked by the same dose of DA. Alpha rANP (10(-5)M) slightly decreased the releases of NE and E from adrenal medulla, and the magnitude of the effect of rANP was smaller than that of DA. MC significantly increased NE and E release even when the adrenal gland was superfused with Ringer's solution containing 10(-5)M of rANP. These data suggest that the release of CA from adrenal medulla may be regulated by DA, and that the receptors specifically binding to DA may exist in adrenal medulla as well as sympathetic presynaps. We concluded that DA (but not ANP) may play an important role in controlling (suppressing) the activity of sympathoadrenomedullary system.

Adrenal Medulla↗
PubMed1986

[Role of renal dopamine receptor in the pathogenesis of hypertension after sodium loading].

UNLABELLED: The purpose of this study is to clarify the role of renal dopamine receptor in the pathogenesis of salt-dependent hypertension. Male Wistar rats were raised under three different conditions, control, 1% NaCl loading (NaCl) and 1% NaCl plus metoclopramide with a dose of 1.5 mg/kg daily (MC), for 2 weeks. Then, renal plasma membranes were prepared by ultracentrifugation method, and maximal binding capacity (Bmax) and dissociation constant (Kd) were determined by Scatchard analysis using 3H-spiperone. And plasma aldosterone and prolactin concentration in these three groups were measured by radioimmunoassay. RESULTS: Systolic blood pressure measured tail-cuff method significantly elevated in MC group, but not control and NaCl group. Bmax of renal dopamine receptor was 535.9 +/- 85.0 fmol/mg protein, 594.9 +/- 159.3 fmol/mg protein, 529.1 +/- 166.1 fmol/mg protein, in control, NaCl and MC group, respectively. Kd of renal dopamine receptor in NaCl group was significantly lower than control (p less than 0.05). Renal dopamine contents of NaCl and MC group were lower than control. There was a negative correlation between renal dopamine content and Bmax of renal dopamine receptor in NaCl group (r = -0.95, p less than 0.02). In MC group, plasma aldosterone concentration was slightly higher than control and NaCl group, but there was no differences in plasma prolactin concentration among these three groups.

Aldosterone↗
PubMed1986

Two adult familial cases of selective hypoaldosteronism due to insufficiency of conversion of corticosterone to aldosterone.

A 57-year-old woman (case 1) and her daughter aged 29 (case 2) with hyperkalemia exhibited subnormal plasma aldosterone (ALD) in the face of elevated plasma renin activity. Their physical findings were normal. Their arterial blood gas analysis showed that metabolic acidosis and renal function of these cases were slightly impaired. Urinary 17-OHCS and 17-KS excretions in these cases were normal. Baseline levels of corticosterone (B) and 18-hydroxycorticosterone (18-OH-B) were clearly elevated. Plasma deoxycorticosterone (DOC), B and 18-OH-B as well as cortisol remarkable increased after ACTH injection, but the increase in plasma ALD was very small. Angiotensin II infusion in case 1 resulted in a clear rise in plasma 18-OH-B but in slight depletion of B, and no increase in ALD. 9-alpha-fludrocortisone acetate treatment was performed in case 1. Serum potassium was normalized and blood pressure elevated from 82/52 to 120/78 mmHg. Arterial blood gas analysis was corrected. We concluded that these two cases with subnormal plasma ALD and hyperreninemia may exist as a congenital and familial abnormality of the final step of aldosterone boisynthesis due to the impairment of the conversion of B to ALD.

Adrenocorticotropic Hormone↗