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T Saruta

Publications and source records attributed to T Saruta.

At least 307 records · Page 17Linked to original sources
PubMed1994

Calcium restriction accelerates salt-induced hypertension in young spontaneously hypertensive rats.

To assess the effect of dietary calcium (Ca) and salt on blood pressure and vascular reactivity, 5-week-old male spontaneously hypertensive rats were placed on control (1% Ca diet+tap water), high Na (1% NaCl administered in drinking fluid), low Ca (0.2% Ca diet), and low Ca+high Na intake for 3 weeks (n = 8-10). During the observation period, systolic blood pressure increased in all groups, but the increase was markedly enhanced in the low Ca+high Na group. There were no significant differences in body weight and serum electrolytes. On high Na intakes, urine volume and urinary Na excretion increased and plasma renin activity and aldosterone concentration were suppressed, whereas Ca restriction did not affect these values. The dose-response curves of mesenteric arterial beds for in vitro contraction to norepinephrine (NE) were not affected by dietary manipulations. However, the time from maximum contraction to return to baseline levels of contractility by 10(-4) M NE was significantly prolonged in the low Ca+high Na group. These results indicate that Ca restriction accelerates salt-induced hypertension in young spontaneously hypertensive rats, and the cellular impairment in vascular smooth muscle might, at least in part, participate in the enhanced blood pressure elevation under this condition.

Animals↗
PubMed1993

Interleukin 4 downregulates cell growth and prostaglandin release of human mesangial cells.

Several clinical studies have proposed that a T cell derived cytokine IL-4 is operative in glomerulonephritis; however, its biological activities on renal cells have not been investigated. To elucidate its possible role in glomerulonephritis, we have examined whether IL-4 has effect on cell growth and prostaglandins synthesis using cultured mesangial cells (MC). IL-4 dose-dependently suppressed DNA synthesis and cell proliferation. IL-4 (10 ng/ml) alone did not affect prostaglandin E2 (PGE2) synthesis by mesangial cells, though, it inhibited IL-1 alpha- and TNF alpha-stimulated PGE2 synthesis by 48% and 81%, respectively. Comparable inhibition was observed on the conversion of exogenous arachidonic acid to PGs by IL-1-stimulated cells, suggesting IL-4 down regulates PG endoperoxide synthase activity. These results demonstrated that IL-4 is antagonistic to inflammatory cytokines upon PG synthesis as well as anti-mitogenic with MC.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

[Adrenal incidentaloma].

Recent increased use of ultrasonography and computed tomography (CT) has detected a substantial number of incidentally discovered adrenal tumor (incidentaloma). In our institute the discovery rate of adrenal incidentaloma per number of abdominal CT examinations was 0.43%. Those incidentalomas were incidentally found during examination for abdominal discomfort and lumbar pains or evaluation of the cause of hypertension. In the group study by the research committee on "Disorders of Adrenal Steroid Hormones" under the sponsorship of the Ministry of Health and Welfare of Japan, in 53 of 149 patients with incidentaloma, surgical resection was done during 5 years between 1983 and 1989. The pathological examination of those tumors revealed 67.9% of non-hyperfunctioning adrenocortical adenoma, 9.4% of adrenal cancer, 9.4% of ganglioneuroma, 5.7% of pheochromocytoma, 5.7% of adrenal cyst and 1.9% of myelolipoma. The criteria for resection of adrenal incidentaloma have not been established. However, tumors having a diameter of over 5 cm are generally excised in most institutes. Tumors having a diameter of between 3 cm and 5 cm are usually resected if the shape of the tumor is ambiguous and the margin of the tumor is irregular. Tumors having a diameter of less than 3 cm should be carefully followed up by abdominal CT examination every 6 months.

Adrenal Gland Neoplasms↗
PubMed1993

Study on pharmacokinetics of a new biliary excreted oral angiotensin converting enzyme inhibitor, temocapril (CS-622) in humans.

Despite the usefulness of angiotensin converting enzyme (ACE; EC 3.4.15.1) inhibitors for patients with renal insufficiency, some hesitation has been exercised in applying ACE inhibitors to the treatment of such patients because most ACE inhibitors are excreted mainly into the urine. In this context, development of an ACE inhibitor which is excreted into the bile has been sought. The pharmacokinetic properties of the novel ACE inhibitor, temocapril hydrochloride (temocapril HCl; CS-622), were investigated in six healthy volunteers. This drug is excreted mainly into the bile in animal studies. Temocapril HCl was given in a single dose of 0.5, 1.0, and 2.0 mg, and 36, 44, and 38 per cent of the administered drug was excreted in the feces and 17, 19, and 24 per cent in the urine as the de-esterified active diacid form (the diacid metabolite) within 48 h, respectively. The plasma ACE activity was markedly inhibited. No abnormal clinical findings suggestive of side-effects were observed. Thus, from the pharmacokinetic standpoint, temocapril HCl is expected to be a useful drug for patients with renal dysfunction.

Administration, Oral↗
PubMed1993

The role of cytotoxic macrophages in non-obese diabetic mice: cytotoxicity against murine mastocytoma and beta-cell lines.

The cytotoxicity of macrophages from non-obese diabetic (NOD) mice against murine mastocytoma (P-815), and murine beta-cell lines having the NOD gene background (MIN6N-9a), were examined. Peritoneal exudate cells from 20-week-old mice showed higher cytotoxicity, measured as inhibition of thymidine uptake into P-815, than those from 12-week-old mice (p < 0.01). In cyclophosphamide-injected mice, cytotoxicity of peritoneal exudate cells had increased at 8 days post-injection, at which time the mice were not diabetic. To confirm macrophage cytotoxicity against pancreatic cells and examine its cytolytic mechanism, the cytotoxicity of peritoneal exudate cells from cyclophosphamide-injected NOD mice against MIN6N-9a cells was measured by the chromium release assay. These peritoneal exudate cells showed higher cytotoxicity as compared to those of saline-injected mice (p < 0.001). Macrophages were demonstrated to be the major component of peritoneal exudate cells (50%) by flowcytometric analyses. Cytotoxicity increased with macrophage enrichment by adhesion (p < 0.01). Furthermore, a macrophage toxin, silica, completely blocked the cytotoxicity (p < 0.001). Cytokines (interleukin 1 and tumour necrosis factor) and a nitric-oxide-producing vasodilator, sodium nitroprusside, were cytotoxic to MIN6N-9a cells but only sodium nitroprusside showed cytotoxicity when incubated for the same period as peritoneal exudate cells. Thus, macrophages play an important role in beta-cell destruction and soluble factors other than cytokines (e.g. nitric oxide) may be mediators of this early cytolytic process.

Aging↗
PubMed1993

Efficacy of manidipine in the treatment of hypertension with renal impairment: a multicenter trial.

The effects of 5 to 20 mg/day of manidipine, a dihydropyridine-type calcium channel blocker, on blood pressure and renal function were studied in 71 hypertensive patients with renal impairment (serum creatinine levels between 1.4 and 5 mg/dl). Thirty-two patients were followed for more than 48 weeks, and 22 patients remain on the treatment after 24 to 48 weeks. The study was interrupted in 17 patients. In 32 patients who were followed for more than 48 weeks, blood pressure was well controlled in 21 (65.6%) patients. In seven of these patients alpha beta- or beta-blockers were added to manidipine to control blood pressure. Only 1 of 32 patients whose serum creatinine level was below 3.1 mg/dl showed deterioration of renal function during the 48 weeks. Two of the 17 patients in whom the study was interrupted died of cerebral bleeding or pneumonia. Two patients discontinued the study because of complications of myocardial infarction and retinal infarction, six withdrew because of deterioration in renal function, and the other seven patients withdrew because of poor compliance. From these studies, it was concluded that manidipine is well tolerated and effective in hypertensive patients with renal impairment (serum creatinine levels < or = 3 mg/dl). If blood pressure is not well controlled in these patients, combined treatment with manidipine and alpha beta- or beta-blockers is recommended.

Adult↗
PubMed1993

Effects of alpha 2- and beta-adrenergic agonism on glucagon secretion from perfused pancreata of normal and streptozocin-induced diabetic rats.

Insulin secretion is known to be inhibited by alpha 2-adrenergic agonism and stimulated by beta-adrenergic agonism in both experimental animals and humans. In contrast, adrenergic regulation of glucagon secretion remains controversial. This study was designed to determine the effects of alpha 2- and beta-adrenergic agonism on islet alpha cells, using isolated perfused pancreata of normal and streptozocin-induced diabetic (STZ-D) rats. The alpha 2-adrenoceptor agonist clonidine at a concentration of 10(-7) mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (1,286 +/- 90 v 417 +/- 53 ng/L, P < .01) and STZ-D rats (551 +/- 86 v 130 +/- 19 ng/L, P < .01). Also, the beta-adrenoceptor agonist isoproterenol at a concentration of 10(-7) mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (751 +/- 130 v 347 +/- 41 ng/L, P < .05) and STZ-D rats (182 +/- 22 v 92 +/- 20 ng/L, P < .01). Furthermore, these alpha 2- and beta-agonistic effects were almost completely inhibited in the presence of the alpha 2-adrenoceptor antagonist yohimbine and the beta-adrenoceptor antagonist propranolol at a concentration of 10(-6) mol/L, respectively. Insulin secretion was markedly reduced in STZ-D rats. These results suggest that even in a severely diabetic state, not only beta- but also also alpha 2-adrenergic agonism stimulates glucagon secretion from rat pancreatic alpha cells.

Adrenergic alpha-Agonists↗
PubMed1993

Detection of heat shock protein in patients with insulin-dependent diabetes mellitus.

We have investigated whether antibodies to heat shock protein (hsp) 65 are present in sera from patients with insulin-dependent diabetes mellitus by using Mycobacterium leprae hsp65. Fifty-two sera from patients with IDDM, 36 from patients with unclassified insulin-treated diabetes mellitus and 41 from normal healthy controls were examined by ELISA assay. Seventeen (32.7%) out of 52 IDDM sera and 10 (27.8%) out of unclassified insulin-treated diabetic sera were positive for anti-Mycobacterium (anti-M. leprae) hsp65 antibodies while none of the healthy control sera were positive. Based on western blot analysis, 12 of the 17 IDDM sera and 1 of 2 sera from the unclassified insulin-treated diabetics were positive for anti-M.leprae hsp65 antibodies while all normal control sera were negative. These results support the idea that hsp65 may play a role in the pathogenesis of IDDM. Future studies are necessary to elucidate the role of hsp65 in the pathogenesis of IDDM.

Antibodies, Bacterial↗
PubMed1993

Dissociation of clinical manifestation and histopathology in the course of mesangial injury by anti-thymocyte antibody.

Intravenous administration of heterologous anti-thymocyte antibodies, which react with rat mesangial cells, induced minimal mesangiolysis (6 hours to 3 days) followed by mesangial hypercellularity. Moreover, autologous immunoglobulins appeared in the mesangium within 1 or 2 weeks. At the same time, electron microscopy demonstrated mesangial deposits. Accompanying these pathological alterations, significant proteinuria developed. To accelerate an acute autologous immune reaction, rats were preimmunized with rabbit IgG prior to the injection of anti-thymocyte antibodies. They revealed marked mesangiolytic lesions 3 days after injection with deposition of autologous immunoglobulins and C 3 in the mesangium. In contrast, there was no significant proteinuria. Thus, mild pathological alterations in the mesangium induced by heterologous and subsequent autologous immune reactions caused proteinuria, and accelerated immune injury to the mesangium produced severe mesangiolysis without proteinuria. Based on these findings, it is suggested that the time-lapse between heterologous and autologous immune reactions to the mesangium influences the pathological alterations and clinical manifestations occurring in mesangial injury by anti-thymocyte antibody.

Animals↗
PubMed1993

Role of NO on pressure-natriuresis in Wistar-Kyoto and spontaneously hypertensive rats.

We investigated the role of the endothelium-derived relaxing factor nitric oxide (NO) on pressure-natriuresis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) using in vivo perfusion studies. Differences in the neural and hormonal background to the kidney were minimized by renal denervation and by holding plasma vasopressin, aldosterone, corticosterone, and norepinephrine levels constant by intravenous infusion. In WKY, elevation of renal perfusion pressure (RPP) from 115 to 157 mm Hg increased urinary sodium excretion 4.5 to 14.8 microEq/min/g kidney wt, and the slope of its linear regression was 0.21 microEq/min/g kidney wt/mm Hg. Infusion of an inhibitor of NO synthase, L-NMMA (1 mg/min/kg), lowered this slope (P < 0.05) but L-arginine (3 mg/min/kg) did not change it. By contrast, the impaired pressure-natriuresis response of SHR was ameliorated by L-arginine (slope: 0.08 to 0.16; P < 0.05), while L-NMMA did not blunt it further. GFR and renal plasma flow (RPF) were well autoregulated in both strains, but L-NMMA lowered RPF significantly (SHR: from 4.2 to 2.6 ml/min/g kidney wt; WKY: 4.5 to 2.5 ml/min/g kidney wt). Moreover, when infused simultaneously, all these individual effects of L-NMMA and L-arginine were nullified. These results suggest that NO plays an important role in the pressure-natriuresis mechanism.

Amino Acid Oxidoreductases↗
PubMed1993

Enzymuria in non-insulin-dependent diabetic patients: signs of tubular cell dysfunction.

1. To evaluate tubular damage in diabetic patients, we measured the 24 h urinary excretion of five enzymes (N-acetyl-beta-D-glucosaminidase, gamma-glutamyl transpeptidase, dipeptidyl aminopeptidase IV, alanine aminopeptidase and alkaline phosphatase) that originate in renal proximal tubular cells. 2. Studies were performed on 118 non-insulin-dependent diabetic patients, 59 non-diabetic patients with chronic renal disease and 47 normal control subjects. First, the correlation between renal function, glycaemic control and urinary enzyme excretion was investigated. Secondly, the subjects were treated by controlled diet therapy to assess the effects of better glycaemic control on urinary enzyme excretion. 3. Regardless of a diabetic or non-diabetic cause of renal dysfunction, all of the five enzymes showed abnormal urinary excretion in patients with renal insufficiency (serum creatinine concentration > 2.0 mg/dl). In diabetic patients, however, an increase in N-acetyl-beta-D-glucosaminidase excretion and a decrease in gamma-glutamyl transpeptidase excretion were noted even in those who had no signs of renal dysfunction, including microalbuminuria. Moreover, the excretion of these two enzymes had a higher degree of correlation with glycaemic control and renal function than did that of the other three enzymes. Multiple regression analysis revealed that excretion of N-acetyl-beta-D-glucosaminidase is best correlated with urinary protein (r2 = 0.35), whereas excretion of gamma-glutamyl transpeptidase is closely associated with glomerular filtration rate (r2 = 0.33). 4. In diabetic patients, diet therapy improved glycaemic control but had no effects on renal function, microalbumin excretion and beta 2-microglobulin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1993

Pharmacokinetics of cefuroxime axetil in patients with normal and impaired renal function.

The pharmacokinetics of cefuroxime axetil were studied by a model-independent method after a single oral dose corresponding to 500 mg of cefuroxime in 28 subjects grouped according to renal functions. Creatinine clearance (Clcr) was > 85, 50 to 84, 15 to 49, and < 15 mL/min in groups 1, 2, 3, and 4 respectively. The V(area)/F (distribution volume/bioavailability) was independent of renal function, the average being 0.82 +/- 0.27 L/kg. Both Cls/F (systemic clearance/bioavailability) and Clr (renal clearance) decreased linearly with the decrease in Clcr. The T1/2 (serum half-life) was 1.4 +/- 0.33 h, 2.4 +/- 0.65 h, 4.6 +/- 2.32 h, and 16.8 +/- 10.2 h in groups 1, 2, 3, and 4 respectively. A significant correlation existed between kel (elimination rate constant) and Clcr (r = 0.88, P < 0.01). kel of cefuroxime can be predicted by: kel (h-1) = 0.0046 x Clcr + 0.0108. Based on these data, modification of dosing schedule is not deemed necessary when Clcr is above 50 mL/min/1.73 m2, while the standard individual dose should be given every 12 h when Clcr is 49-30 mL/min/1.73 m2, every 24 h when it is 29-10 mL/min/1.73 m2, and every 48 h when it is below 10 mL/min/1.73 m2.

Adult↗
PubMed1993

Impaired insulin sensitivity in young, lean normotensive offspring of essential hypertensives: possible role of disturbed calcium metabolism.

OBJECTIVES: To determine whether insulin sensitivity is impaired in normotensive offspring of essential hypertensives and to investigate how it relates to disturbed calcium metabolism. DESIGN: In 10 young lean, normotensive subjects with family histories of essential hypertension and in 10 age-matched controls we investigated insulin sensitivity by the euglycaemic hyperinsulinaemic clamp technique, and 75-g oral glucose tolerance test (GTT). We simultaneously measured calcium-related factors, including the intracellular calcium concentration in platelets. RESULTS: Insulin-induced glucose uptake was significantly impaired in subjects with positive compared with in subjects with negative family history of essential hypertension. Intracellular calcium concentration was significantly higher in subjects with positive than in those with negative family history. Insulin sensitivity was inversely correlated with intracellular calcium concentration (r = -0.56; P < 0.05). Those who showed a higher intracellular calcium concentration had impaired insulin sensitivity. Oral GTT results were normal in both groups. CONCLUSION: Impaired insulin sensitivity and disturbed calcium metabolism exist before the onset of hypertension. Insulin sensitivity correlates inversely with intracellular calcium concentration. These findings suggest that the association of the impaired insulin sensitivity and disturbed calcium metabolism may contribute to the development of hypertension.

Adult↗
PubMed1993

Role of L-arginine-nitric oxide pathway in hypertension.

OBJECTIVE: The present study was designed to investigate the effect of L-arginine administration on patients with essential and secondary hypertension by measuring haemodynamic parameters, neuroendocrine hormones and indicators of nitric oxide (NO) release. DESIGN: Ten patients with essential hypertension and six with secondary hypertension (three with renovascular hypertension and three with primary aldosteronism) were enrolled in the study. METHODS: L-Arginine was administered intravenously to the hypertensive patients. During L-arginine administration, blood pressure, heart rate, cardiac output and neuroendocrine hormones such as catecholamines, plasma renin activity and plasma aldosterone were measured. To examine whether L-arginine administration increases NO production, indicators of NO release in vivo such as plasma cyclic GMP, plasma citrulline and urinary excretion of nitrite and nitrate were measured simultaneously. RESULTS: During administration, mean arterial pressure decreased, heart rate increased, cardiac output increased and total peripheral resistance decreased. The indicators of NO release increased simultaneously during administration. Catecholamine and plasma renin activity, rather than increasing in response to L-arginine-induced hypotension as expected, showed no significant changes except in patients with renovascular hypertension. In all patients plasma aldosterone levels decreased significantly in response to L-arginine administration, regardless of basal plasma renin activity and aldosterone levels. CONCLUSIONS: These results suggest that exogenous L-arginine produces a vasodilatory effect by increasing NO production and that L-arginine, or released NO, modulates the release of neuroendocrine hormones in hypertensive subjects.

Adult↗
PubMed1993

Serious adverse effects induced by simultaneous administration of two nonsteroidal anti-inflammatory drugs.

We have described the case of a 58-year-old woman in whom acute hemolytic anemia, renal failure, and granulocytopenia developed after intake of mefenamic acid and diclofenac. Results of direct and indirect Coombs' tests were negative, but the lymphocyte transformation test was positive for these two nonsteroidal antiinflammatory drugs (NSAIDs). We suggest that the immune complex mechanism could have induced these adverse reactions. Although these drugs are very popular, simultaneous administration should be avoided because serious adverse effects can potentially occur.

Acute Kidney Injury↗
PubMed1993

Arginine vasopressin produces renal vasodilation via V2 receptors in conscious dogs.

In conscious dogs, 36-h water deprivation induced a significant increase in renal blood flow (RBF) with elevation of the plasma arginine vasopressin (AVP) concentration to 9.6 +/- 1.8 pg/ml. To simulate such a condition, a mild elevation of plasma AVP was produced by infusing AVP intravenously at a dose of 0.1 ng.kg-1.min-1 for 20 min. The plasma AVP concentration then increased to 6.8 +/- 0.7 pg/ml. This dose of AVP increased the RBF by 21.7 +/- 2.6% and decreased the renal vascular resistance by 18.1 +/- 2.3% without significant changes in mean arterial pressure, cardiac output, or heart rate. The mechanism of this renal vasodilatory action was examined using newly developed, orally effective, selective AVP antagonists OPC-21268 (a V1-receptor antagonist) and OPC-31260 (a V2-receptor antagonist). In 36-h water-deprived dogs, V2-receptor blockade with OPC-31260 significantly decreased the RBF by 20.5 +/- 2.6% without significant changes in cardiac output. The exogenous AVP-induced renal vasodilatory response tended to be augmented when V1 receptors were blocked by pretreatment with OPC-21268, but the change did not achieve statistical significance. On the other hand, V2-receptor blockade by either pretreatment with OPC-31260 or simultaneous infusion of OPC-31260 inhibited this vasodilatory response. Furthermore, intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP) at a dose of 0.3 ng.kg-1 x min-1 for 20 min significantly increased the RBF by 36.5 +/- 1.7%, and this DDAVP-induced renal vasodilation was inhibited by simultaneous infusion of V2-receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of in vivo and in vitro alkali treatment on intracellular pH regulation of OMCDis cells.

To examine functional changes of the transporters in the inner stripe of the outer medullary collecting ducts (OMCDis) by the peritubular acid-base status, in vitro microperfusion using the acetoxymethyl ester of 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein was performed. Cell alkalinization systems were assessed by the recovery rate (dpHi/dt) of intracellular pH (pHi) after intracellular acid loading by NH(4+)-NH3 prepulse with bath amiloride. In alkali-loaded rabbits (0.15 M NaHCO3 drinking for 14 days), dpHi/dt showed a significant decrease (1.80 +/- 0.29 pH units/s x 10(3)) compared with either control (3.30 +/- 0.59) or acid-loaded rabbits (0.15 M NH4Cl drinking for 14 days, 3.05 +/- 0.46). The difference of dpHi/dt between control and alkali-loaded rabbits was eliminated by lumen N-ethylmaleimide (NEM), suggesting that H+ pump activity was decreased. The effect of in vitro alkali treatment (50 mM HCO3-, pH 7.7) for 3-4 h was also examined. This incubation significantly decreased the dpHi/dt (1.83 +/- 0.35) compared with the time control experiments (3.18 +/- 0.28), whereas no significant difference was seen in the presence of lumen NEM. Anion exchanger activity, as determined from the pHi changes after Cl- addition to the bath, showed no significant change with in vivo or in vitro alkali treatment. The results indicate that cell function of the OMCDis is regulated in response to the peritubular acid-base environment via changes in the H(+)-adenosinetriphosphatase.

Amiloride↗