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Biomedical subjects

S Shigetomi

Publications and source records attributed to S Shigetomi.

At least 37 records · Page 2Linked to original sources
PubMed1994

Dopaminergic abnormalities in hypertension associated with moderate renal insufficiency.

To evaluate the additive effect of moderate chronic renal failure to the abnormal dopamine generation and action observed in stable hypertension, we investigated 22 age-matched patients with a comparable degree of hypertension with and without chronic renal failure. Both groups were compared with each other and with an age-matched control group after a single oral dose of dihydroxyphenylalanine (DOPA) while cardiorenal responses and DOPA, dopamine, and their metabolites were measured. The hypertensive patients with chronic renal failure shared with their hypertensive counterparts without chronic renal failure an impaired DOPA decarboxylation to dopamine. However, patients with chronic renal failure had decreased hemodynamic and normal natriuretic responses compared with the hypernatriuresis of hypertensive patients with normal renal function; patients with chronic renal failure had elevated basal plasma concentrations of DOPA and dopamine sulfates as well as increased plasma and urinary DOPA sulfate but blunted urinary dopamine sulfate increases after DOPA administration; they presented augmented plasma atrial natriuretic factor concentrations. Thus, hypertensive patients with moderate chronic renal failure exhibit a decreased hemodynamic responsiveness to DOPA administration-induced dopamine elevation but with the natriuretic effect of dopamine maintained (possibly because of its permissive interaction with increased atrial natriuretic factor levels). Hypertensive patients with chronic renal failure have a heightened DOPA and dopamine sulfoconjugating propensity. Dopamine sulfate attenuates the biologic action of free dopamine. This may contribute (possibly via glomerular hypertension and hyperfiltration due to decreased postglomerular vasodilation) to progressive hypertensive renal damage, particularly in groups predisposed to dopamine deficiency, such as diabetics, blacks, and the elderly.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Recent aspect of the role of peripheral dopamine and its receptors in the pathogenesis of hypertension.

Dopamine is an essential and indispensable catecholamine, which acts not only as a neurotransmitter in dopaminergic and noradrenergic sympathetic neurons but also as an autocrine/paracrine substance in non-neuronal tissues. The regulatory mechanism of dopamine synthesis in neuronal tissues seems to be different from that in non-neuronal tissues. Among receptors specifically bound to dopamine, five different receptors have already been cloned. Dopamine exhibits vasodilative and natriuretic effects by stimulating specific dopamine receptors located in renal tubular cells, blood vessels, etc. Physiological effects of dopamine appear to be protective against hypertension and sodium retention. Spontaneously hypertensive rats (SHR) are known to have an enhanced dopamine generation associated with the increased sympathetic nervous activity. A defect of renal D1-receptor-mediated coupling to adenylate cyclase has also been demonstrated in SHR. On the other hand, it has been reported that Dahl salt sensitive rats exhibit defective dopamine synthesis during high salt intake, which may be a definitive abnormality in this strain. The pathophysiological role of peripheral dopamine is essential hypertensive patients is still controversial. Considering the previous studies, it seems to be the case that essential hypertensive patients with increased sympathoadrenergic activity show enhanced dopaminergic discharge where dopamine may negatively modulate high blood pressure, and that stable essential hypertensive patients with salt-sensitivity and/or suppressed renin activity show insufficient dopamine synthesis in the kidney.

Animals↗
PubMed1993

Defective 3,4-dihydroxyphenylalanine decarboxylation to dopamine in hydralazine-treated hypertensive patients may be pyridoxine remediable.

The previously observed defective dopamine (DA) generation from 3,4-dihydroxyphenylalanine (DOPA) can also be seen in patients treated for many years by hydralazine. This may be due to a hydralazine-induced depletion of pyridoxine, an essential coenzyme of the aromatic L-amino acid decarboxylase (LAAD). Eleven hydralazine-treated stable essential hypertensive (EH) patients, initially found to have a defect in the DOPA decarboxylation to DA, tested by a single DOPA administration (500 mg, orally), were retested by the same test 4 days after pyridoxine pretreatment (100 mg/day) for data on blood pressure (BP), pulse rate, and renal and plasma catecholamines and their metabolites, as well as plasma atrial natriuretic factor (ANF), cyclic GMP (cGMP), plasma renin activity (PRA), and plasma aldosterone (PA). Initially, hydralazine-treated stable EH patients manifested, following DOPA administration, lower DOPA decarboxylation to DA than control subjects. Pyridoxine pretreatment accelerated DA generation from exogenous DOPA and attenuated the DOPA-induced increases in plasma and urinary DOPA and its metabolite 3-O-methyl-DOPA, but accentuated the increase in free DA and its main metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), while BP, ANF, cGMP, PRA, and PA remained unaffected. The DOPA-induced increments of urinary DA were, in contrast to plasma DA changes, blunted by pyridoxine pretreatment. The attenuation of the sodium excretion by pyridoxine pretreatment exceeded that of the DA excretion, suggesting that pyridoxine suppressed a natriuretic factor, other than ANF, or activated a sodium-retaining factor, other than renin or aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗