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E Ogata

Publications and source records attributed to E Ogata.

At least 163 records · Page 9Linked to original sources
PubMed1991

Effect of salt loading on aldosterone response to long-term infusion of angiotensin II in rats.

We examined changes in plasma aldosterone level and blood pressure (BP) after long-term (12 days) intravenous infusion of angiotensin II (Ang II; 15 and 60 ng/min) with two different sodium intakes (0.66% and 8% salt-containing diet) in Wistar rats. Without salt loading, 15 ng/min of Ang II did not increase mean BP (112 +/- 1 vs. 112 +/- 2 mm Hg), but 60 ng/min of Ang II increased mean BP (144 +/- 3 mm Hg, p less than 0.01). However, the 8% salt diet not only enhanced the pressor effect of 60 ng/min Ang II (168 +/- 9 mm Hg, p less than 0.05), but also elevated mean BP with 15 ng/min of Ang II (159 +/- 3 mm Hg, p less than 0.01). On a normal-salt diet (0.66%), plasma aldosterone was increased by Ang II infusion from 11.3 +/- 0.3 ng/dl to 12.7 +/- 0.5 ng/dl (NS) at a rate of 15 ng/min Ang II, and to 15.7 +/- 0.4 ng/dl (p less than 0.01) at 60 ng/min Ang II. However, salt loading reduced Ang II-induced elevation of aldosterone: 11.3 +/- 0.5 ng/dl (less than 0.01) at a rate of 60 ng/min Ang II. Thus, salt loading diminished aldosterone response to Ang II, which might compensate salt-induced enhancement of the pressor effect of Ang II.

Aldosterone↗
PubMed1991

Mechanism of glycogenolytic action of histamine in rat hepatocytes.

The mechanism by which histamine induces glycogenolysis was investigated in rat hepatocytes. Histamine induced stimulation of glucose output in hepatocytes in a dose-dependent manner. The maximal effect of the glycogenolytic action of histamine, which was approximately 60% of the maximal glucagon action, was obtained at 10(-6) M. These effects were inhibited by H1 receptor antagonists triprolidine hydrochloride and tripelennamine but not by a H2 receptor antagonist cimetidine. Histamine also increased the activity of phosphorylase a. When 10(-6) M histamine and 5 x 10(-9) M glucagon were added simultaneously, the actions of these two agents were additive. In contrast, there was no additivity when 10(-6) M histamine and 10(-8) M angiotensin II were added. Histamine did not increase adenosine 3',5'-cyclic monophosphate at any doses tested but induced a rapid increase in the cytoplasmic free calcium concentration ([Ca2+]c). Histamine increased [Ca2+]c even in the presence of 1 microM extracellular calcium, an observation suggesting that histamine caused calcium release from an intracellular calcium pool(s). When [3H]inositol-labeled hepatocytes were incubated with histamine, radioactivity in the D-myo-inositol trisphosphate fraction was rapidly increased. These results indicate that histamine acts on rat hepatocytes mainly via H1 receptors and stimulates glycogenolysis by activating the calcium messenger system.

Angiotensin II↗
PubMed1991

High-potassium diet attenuates salt-induced acceleration of hypertension in SHR.

We studied the effects of K supplementation (8% KCl) for 4 wk on blood pressure (BP), Na space, and renal hemodynamics in 5-wk-old, spontaneously hypertensive rats (SHR) or age-matched Wistar-Kyoto rats (WKY) eating normal-NaCl (0.66%) or high-NaCl (8%) diet. In WKY, high-Na and/or high-K diets had no effects on BP. In SHR, Na load accelerated the development of hypertension, whereas K supplementation did not affect BP of normal-Na SHR but attenuated the increase in BP with Na load. Correspondingly, Na load in SHR significantly increased renal vascular resistance (RVR), and K supplementation attenuated the increased RVR of Na-loaded SHR. Moreover, Na space of SHR was increased compared with that of WKY, and although Na load did not affect Na space, K supplementation tended to decrease Na space in SHR. These results indicate that 9-wk-old SHR is relatively volume-expanded compared with age-matched WKY, and K supplementation could improve the lowered slope of the pressure-Na excretion relationship in SHR, resulting in maintenance of Na balance. Thus the data suggest that changes in RVR, which might be intimately related to renal function for Na excretion, contribute to both salt sensitivity of SHR and antihypertensive action of K supplementation in Na-loaded SHR.

Animals↗
PubMed1991

High potassium intake attenuates antinatriuretic response to air stress in DOCA-salt rats.

We studied the effects of potassium supplementation (2 wk of 0.5% KCl to drink) on responses of renal function to a stressful environmental stimulus (air stress) in deoxycorticosterone acetate (DOCA)-salt rats. In conscious DOCA-salt rats, air stress decreased urine flow rate and urinary sodium excretion without changes in effective renal plasma flow and glomerular filtration rate, whereas in normotensive vehicle-treated rats air stress had no effect on these measures. Renal denervation abolished the antidiuretic and antinatriuretic responses to air stress in DOCA-salt rats. Correspondingly potassium supplementation in DOCA-salt rats could not only reduce basal blood pressure significantly but also attenuate the antidiuretic and antinatriuretic responses to air stress without renal denervation. Evidence suggests that the attenuation by potassium supplementation of air stress-induced decrease in urine flow and sodium excretion in DOCA-salt rats may be partly involved in the natriuretic and the resultant antihypertensive actions of potassium in DOCA-salt hypertensive rats, but the mechanisms could not be clarified by the present study.

Air↗
PubMed1991

Antihypertensive effect of dietary calcium loading in angiotensin II-salt rats.

To clarify the hypotensive effect of high dietary Ca intake on salt-sensitive hypertension, 7-wk-old Sprague-Dawley rats, 3.15% Na and/or 4.07% Ca diet loaded, were administered 125 ng/ml of angiotensin II (ANG II) intraperitoneally for 12 days. Compared with control rats (mean blood pressure 108 +/- 2 mmHg), ANG II administration caused hypertension (131 +/- 4 mmHg, P less than 0.05). Na loading enhanced the hypertensive effect of ANG II (161 +/- 4 mmHg, P less than 0.01). Dietary Ca loading did not significantly inhibit the pressor effect of ANG II alone (119 +/- 4 mmHg). However, Ca loading suppressed hypertension in ANG II-salt rats (126 +/- 4 mmHg, P less than 0.01). Plasma total catecholamine (norepinephrine + epinephrine) was increased in ANG II-salt rats (176 +/- 14 vs. 290 +/- 23 pg/ml, P less than 0.05), but Ca loading decreased plasma catecholamine (182 +/- 13 pg/ml, P less than 0.05). In contrast, plasma catecholamine was not significantly different between ANG II-treated rats with and without Ca loading. Ca loading increased serum Ca in ANG II rats (10.9 +/- 0.1 vs. 11.7 +/- 0.1 mg/dl, P less than 0.05) but did not do so significantly in ANG II-salt rats (10.8 +/- 0.2 vs. 10.9 +/- 0.1 mg/dl). Thus Ca loading exclusively ameliorated salt-sensitive hypertension, which was induced with ANG II administration and Na loading in rats, probably through suppression of the increased sympathetic activity. In addition, these effects of Ca loading were not mediated through an increased blood level of Ca.

Angiotensin II↗
PubMed1991

Endothelin 1 increases cell calcium in mouse collecting tubule cells.

Effects of endothelin 1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) were examined in superfused single-nephron segments dissected from mouse kidney. ET-1, 10(-9) to 10(-6) M, caused a biphasic increase in [Ca2+]i consisting of an initial rapid rise followed by a second more sustained elevation in [Ca2+]i in cortical collecting tubules (CCT), outer medullary CT (OMCT), and inner medullary CT (IMCT). The magnitude of the response was dose dependent and was greater in CCT than in OMCT or IMCT. Additional studies using CCT revealed that Ca2+ removal from the superfusate resulted in attenuation of the second phase of [Ca2+]i with approximately 50% reduction in the height of the initial [Ca2+]i peak in response to 10(-6) M ET-1. Ca2+ channel blocker nicardipine had little effect on ET-1-evoked changes in [Ca2+]i. BAY K 8644 and high superfusate K+ also did not affect [Ca2+]i. Addition of ET-1 and arginine vasopressin (AVP), 10(-6) M each, showed the presence of homologous desensitization but the absence of heterologous desensitization in [Ca2+]i changes. There was no additive effect of ET-1 and AVP on [Ca2+]i when they were added together. These data show that ET-1 evokes a biphasic increase in [Ca2+]i of collecting tubules and suggest that the initial peak of the ET-1-evoked rise in [Ca2+]i is largely due to cell Ca2+ release and that the second sustained rise in [Ca2+]i is largely due to increased Ca2+ influx. Data also suggest that ET-1 and AVP may act in the collecting tubules through different receptors.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Ion channel activities of cultured rat mesangial cells.

We used the patch-clamp technique to clarify the nature of ion channels in renal mesangial cells in culture. In the cell-attached mode most patches were silent in the absence of agonists. In some patches a 25-pS nonselective channel was observed. This 25-pS cation channel was consistently observed in inside-out patches, and it was activated by intracellular Ca2+. Excised patch experiments also revealed the existence of a 40-pS K+ channel, which was activated by intracellular Ca2+. This 40-pS K+ channel was observed infrequently in the cell-attached mode. The activities of both channels were increased by arginine vasopressin or angiotensin II, resulting from an increase in intracellular Ca2+ concentration.

Angiotensin II↗
PubMed1991

Circulating bone Gla protein in end-stage renal disease determined by newly developed two-site immunoradiometric assay.

As a marker for bone formation, bone Gla protein (BGP) levels in the circulation have been measured in clinical research and management for metabolic bone diseases. We evaluated the clinical availability of a newly developed two-site immunoradiometric assay (IRMA) for human BGP and determined the serum BGP concentrations using this methodology in patients with abnormal calcium metabolism including those with end-stage renal disease undergoing maintenance dialysis. A cross-reactivity test revealed that this assay system specifically recognizes intact molecules (1-49) of BGP and excludes fragments of the molecules (1-19, 12-33, 23-33). Serum BGP levels in dialysis patients were positively correlated with those by conventional radioimmunoassay (RIA) (r = 0.918, p less than 0.00001, n = 37) as well as normal individuals (r = 0.935, p less than 0.0001, n = 16). However, the levels of BGP determined by IRMA were estimated to be significantly lower than those by RIA (23.6 +/- 9.8 vs. 29.6 +/- 9.1 ng/ml, p less than 0.00001). These results suggest that this IRMA system, with a rapid and easy procedure, excludes fragment forms of BGP in the circulation, which are found in uremic sera and probably attributed to increased bone resorption. Further studies are needed to ensure that serum intact BGP levels mainly reflect BGP production in osteoblasts, particularly in end-stage renal disease.

Female↗
PubMed1991

Role of chloride in angiotensin II-induced salt-sensitive hypertension.

The present study investigated the effect of the anion accompanying sodium on the development of angiotensin II-induced hypertension in rats and the role of the sympathetic nervous system and extracellular fluid volume in its mechanism. Hypertension was induced by intraperitoneal infusion of angiotensin II (125 ng/min) for 12 days via miniosmotic pump. High dietary intake of sodium chloride significantly augmented the angiotensin II-induced hypertension (mean blood pressure on day 13, 165 +/- 6 versus 142 +/- 6 mm Hg, p less than 0.05), but equimolar sodium loading provided as sodium citrate failed to enhance angiotensin II hypertension (140 +/- 6 mm Hg). Plasma norepinephrine concentration in the conscious, resting state increased with sodium chloride loading in angiotensin II-infused rats (594 +/- 42 versus 312 +/- 37 pg/ml, p less than 0.01), but it remained unchanged with sodium citrate loading (324 +/- 23 pg/ml). Correspondingly, maximum response to hexamethonium bromide, a ganglion blocker, was greater in sodium chloride-loaded angiotensin II rats (77.7 +/- 4.6 mm Hg) than that in angiotensin II (59.7 +/- 5.1 mm Hg) or in sodium citrate-loaded angiotensin II (57.7 +/- 4.2 mm Hg) rats. Moreover, extracellular fluid volume, measured as Na2(35)SO4 space, increased in sodium chloride-loaded angiotensin II rats (427 +/- 18 ml/kg body wt) as compared with that in angiotensin II rats (375 +/- 15 ml/kg body wt) but not when compared with volume in sodium citrate-loaded angiotensin II (389 +/- 7 ml/kg body wt) rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

A novel vitamin D3 analog, 22-oxa-1,25-dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia.

Although 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has been shown to inhibit the growth of certain malignant cells, its hypercalcemic effect has prevented clinical application. We have recently developed a novel vitamin D3 analog, 22-oxa-1,25-(OH)2D3 (OCT), that is capable of promoting differentiation and inhibiting proliferation without inducing hypercalcemia. The present study was undertaken to determine whether OCT could be applied for the treatment of breast cancer with or without estrogen receptor (ER). OCT inhibited the proliferation of both ER-positive (MCF-7, T-47D, and ZR-75-1) and ER-negative breast cancer cells (MDA-MB-231 and BT-20) in vitro in a time- and dose-dependent manner, as determined by cell number and [3H]thymidine uptake. The antiproliferative effect was observed with a concentration as low as 10(-11) M OCT, and treatment of MCF-7 cells with 10(-8) M OCT for 8 days caused more than a 50% reduction in cell number compared with that of vehicle-treated cells. OCT was approximately 1 order of magnitude more potent than 1,25-(OH)2D3 in inhibiting the proliferation of MCF-7 cells. The in vivo effect of OCT was examined in athymic mice implanted with ER-negative MX-1 tumor, which was established as the xenograft derived from human breast carcinoma. Intratumor administration of OCT three times a week remarkably delayed the growth of MX-1 tumor in a time- and dose-dependent manner. The antitumor effect of 1 microgram/kg BW OCT was greater than that of 500 microgram/kg BW adriamycin, and the relative tumor weights in each group on day 26 were 29.7% and 50.5% of that in the vehicle-treated group, respectively. The effects of OCT and adriamycin were additive, and the relative tumor weight after 26 days of combined treatment was 21.7% of that in the vehicle-treated group. Oral administration of OCT was also effective, and the relative tumor weight in the OCT-treated group (1 microgram/kg BW) was 54.6 +/- 0.1% (mean +/- SEM) of that in the vehicle-treated group. Neither intratumor nor oral administration of OCT raised the serum calcium level in these animals. These results demonstrate that OCT is a potent inhibitor of the proliferation of breast cancer cells with or without ER and that OCT inhibits the growth of breast cancer in vivo without inducing hypercalcemia. We suggest that OCT may provide a new strategy for the treatment of breast carcinoma regardless of ER status.

Animals↗
PubMed1991

Pheochromocytoma with pyrexia and marked inflammatory signs: a paraneoplastic syndrome with possible relation to interleukin-6 production.

Pheochromocytoma can cause several paraneoplastic syndromes. We report a patient with pheochromocytoma who exhibited pyrexia and marked inflammatory signs along with an elevated serum interleukin-6 (IL-6) level. All of these abnormalities disappeared and serum IL-6 became undetectable by removal of the tumor. In addition, immunohistochemical analysis revealed the presence of IL-6 in the tumor cells. It is suggested that pyrexia and the elevation of acute phase proteins can be a paraneoplastic syndrome with pheochromocytoma, and that the elaboration of IL-6 from pheochromocytoma may play an important role in the development of the syndrome.

Adrenal Gland Neoplasms↗
PubMed1991

Salt sensitivity in Goldblatt hypertensive rats--role of extracellular fluid volume and renin-angiotensin system.

Effects of a high-salt diet on blood pressure, extracellular fluid volume, and the renin-angiotensin system in rats with the two types of Goldblatt hypertension were examined. Both in one-kidney, one clip (1K1C) rats and in one-kidney, sham-clipped (1K) rats, systolic blood pressures of rats which received a high-salt diet for 4 weeks were higher than those of rats of respective groups on a normal-salt diet, suggesting an increased sensitivity of blood pressure to changes in salt intake. Whereas sodium space was increased in 1K rats on the high-salt 1K1C rats receiving the high-salt did not have significantly increased sodium space. These results suggest that acceleration of 1K1C hypertension with salt load could not be explained only by changes in extracellular fluid volume. In contrast, both in two-kidney, one clip (2K1C) rats and in two-kidney, sham-clipped (2K) rats, the high-salt diet produced no change in blood pressure despite the increase in sodium space, suggesting a decreased salt sensitivity. Although on the normal-salt diet the blood pressure of 2K1C rats tended to correlate with plasma renin activity, on the high-salt diet plasma renin activity was markedly decreased, and then blood pressure highly correlated with sodium space. Accordingly, the lesser salt sensitivity in 2K1C rats is probably attributable to the counterbalance of the suppressed renin-angiotensin system against volume expansion. Evidence presented suggests, therefore, that 1K1C rats have greater salt sensitivity of blood pressure than 2K1C rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Hypotensive action of taurine in DOCA-salt rats--involvement of sympathoadrenal inhibition and endogenous opiate.

We studied the roles of the sympathoadrenal system and endogenous opiate in the antihypertensive effects of supplementation of dietary taurine, a sulfur amino acid, in deoxycorticosterone acetate (DOCA)-salt rats. Supplementation of 1% taurine in drinking water for 2 weeks was found to prevent the increase in systolic blood pressure of DOCA-salt rats (116 +/- 2 vs 138 +/- 2 mmHg, p less than 0.01), but failed to effect the systolic blood pressure of vehicle-treated control rats (115 +/- 2 vs 112 +/- 3 mmHg), taurine supplementation restored to normal increased plasma norepinephrine (326 +/- 32 vs 531 +/- 67 pg/ml, p less than 0.01) and epinephrine (204 +/- 19 vs 304 +/- 43 pg/ml, p less than 0.05) concentrations in DOCA-salt rats, but had no effect on norepinephrine (346 +/- 23 vs 338 +/- 33 pg/ml) or epinephrine (198 +/- 17 vs 224 +/- 26 pg/ml) concentrations in control rats. Accordingly, the increased epinephrine content in the adrenals of DOCA-salt rats was normalized with the supplementation of taurine, associated with a markedly increased adrenal taurine content. In conscious rats, moreover, intraperitoneal injection of naloxone (2 mg/kg), a specific opiate antagonist, increased systolic blood pressure only in taurine-supplemented DOCA-salt rats. Evidence presented suggests, therefore, that both the suppression of the increased sympathoadrenal activity and the activation of endogenous opiate might contribute to the antihypertensive effect of taurine in DOCA-salt rats.

Adrenal Glands↗
PubMed1991

Spot determinations of urinary cortisol for the screening of Cushing's syndrome.

The usefulness of spot determination of urinary cortisol in the screening of Cushing's syndrome was evaluated by measuring the cortisol concentration in randomly sampled urine in 68 normal subjects and in 9 patients with Cushing's syndrome. The urinary cortisol concentration in the morning was significantly higher in patients with Cushing's syndrome but some overlap existed between normal subjects and patients with Cushing's syndrome. In contrast, there was a clear discrimination between two groups when urinary cortisol was measured in the late evening: urinary cortisol was lower than 75 micrograms per gram creatinine (microgram/gCr) in normal subjects but higher than 150 micrograms/gCr in patients with Cushing's syndrome. When 1 mg dexamethasone was administered at 2300 h in the evening, spot urinary cortisol the next morning was less than 80 micrograms/gCr in normal subjects while it was above 100 micrograms/gCr in patients with Cushing's syndrome. Dexamethasone-induced suppression of urinary cortisol in normal subjects lasted until late in the afternoon, which allows sampling of urine at any time in the morning and possibly in the afternoon. These results suggest the usefulness of spot determination of urinary cortisol in the screening of Cushings' syndrome.

Adolescent↗
PubMed1991

Inhibition of growth hormone secretion by activin A in human growth hormone-secreting tumour cells.

Effect of activin A on growth hormone secretion was studied in primary culture of 8 human GH-secreting adenomas, which were responsive to TRH in vivo. When studied in vitro, basal GH secretion was reduced in all cases when cells were pre-incubated for 48 h with activin A at a concentration of 5 X 10(-9) mol/l or greater. Pretreatment of GH-secreting cells with 1 X 10(-9) mol/l activin A did not affect either basal secretion or cellular content of GH. These tumour cells also responded to TRH in vitro and the GH response to TRH was completely blocked in cells pretreated with activin A. Activin A slightly reduced the increase in cytoplasmic free calcium concentration induced by TRH. Furthermore, pretreatment of the cells with activin A attenuated GH secretion induced by A23187 or 12-O-tetradecanoyl phorbol-4-acetate, agents which bypass receptor-mediated generation of second messengers. These results indicate that activin A inhibits GH secretion by directly acting on human GH-secreting cells and that activin A inhibits the action of TRH by acting on multiple steps in the messenger system.

Activins↗
PubMed1991

Inherited primary hypothyroidism with thyrotrophin resistance in Japanese cats.

Mutant cats were developed with non-goitrous primary hypothyroidism. They were clinically characterized by severely retarded growth, mild anaemia and high mortality in the young. They responded markedly to thyroid hormone replacement. Thyroid glands in the mutants were normal in position but slightly reduced in size. Laboratory studies revealed low serum concentrations of thyroxine (T4) and tri-iodothyronine (T3), and increased serum concentrations of TSH. Administration of TRH induced no further increase in TSH. Administration of exogenous TSH after suppression of endogenous TSH by T3 did not increase the serum concentration of T4 in the mutants, in sharp contrast with the threefold increase in serum T4 observed in the normal litter-mates. These findings suggest that the underlying pathogenesis of this disorder is unresponsive to TSH. Moreover, we found that the mutants were transmitted in an autosomal recessive manner.

Animals↗