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T Saruta

Publications and source records attributed to T Saruta.

At least 325 records · Page 18Linked to original sources
PubMed1993

Segmental differences in angiotensin receptor subtypes in interlobular artery of hydronephrotic rat kidneys.

Recent studies demonstrate that angiotensin II (ANG II)-induced vascular action is mediated preferentially by AT1 receptors. Although autoradiographic studies indicate the presence of AT2 receptors in large preglomerular vessels, functional roles for AT2 receptors in ANG II-induced renal vasoconstriction remain undetermined. We examined the effects of DuP-753 and PD-123319 on ANG II-induced vasoconstriction of interlobular arteries (ILA) in isolated perfused hydronephrotic rat kidneys to directly assess the AT1- and AT2-mediated action of ANG II on renal microvessels. Both DuP-753 (0.1-10 microM) and PD-123319 (0.1-10 microM) elicited dose-dependent vasodilation of ANG II-induced ILA constriction, with 86 +/- 4% and 36 +/- 4% inhibition by 10 microM DuP-753 and PD-123319, respectively. The reversal by DuP-753 of ANG II-induced ILA vasoconstriction was greater in small-caliber segments than in large-caliber segments. In contrast, the ability of PD-123319 (10 microM) to inhibit the vasoconstriction was augmented as the vessel diameter increased (slope = +0.46, correlation coefficient = +0.68; P < 0.01). Thus, although AT1 predominantly mediates the ANG II-induced ILA vasoconstriction, PD-123319-sensitive ANG II receptors (e.g., AT2 or AT1B) may also participate partly in the ILA vasoconstriction, particularly at large-caliber segments. In conclusion, distribution of ANG II receptor subtypes may differ depending on the size of the renal microvasculature.

Angiotensin II↗
PubMed1993

Steroid-responsive renal insufficiency due to idiopathic granulomatous tubulointerstitial nephritis.

A 26-year-old male was admitted to our hospital having suffered from subfever, sterile pyuria and renal insufficiency for 1 year. There had been no apparent hematuria/proteinuria, and evidence of infection, allergy or intoxication was not demonstrated. Open renal biopsy revealed severe tubulointerstitial changes with granuloma accompanied by neither caseous necrosis nor giant cells. Infiltrating cells mostly consisted of CD4 and CD8 T cells, and some proximal tubular cells presented MHC class II antigen. Following the negative culture of biopsied specimen for acid-fast bacilli, diagnosis of idiopathic granulomatous tubulointerstitial nephritis was made, and steroid therapy was started. Two months later, pyuria disappeared and renal function improved significantly, proving the effectiveness of steroid on idiopathic granulomatous tubulointerstitial nephritis.

Adult↗
PubMed1993

Central and peripheral vasopressin interact differently with sympathetic nervous system and renin-angiotensin system in renal hypertensive rabbits.

This study was designed to elucidate how central and peripheral arginine vasopressin (AVP) interacts with the sympathetic nervous system and the renin-angiotensin system to maintain blood pressure in two-kidney, one-clip hypertensive rabbits. We recorded renal sympathetic nerve activity (RSNA) in the conscious state as an index of sympathetic nervous system function. The changes in mean arterial pressure, heart rate, and RSNA were recorded continuously for 60 minutes after intravenous administrations of captopril (2.5 mg/kg) and nicardipine (3.2 micrograms.kg-1.min-1) in eight identical rabbits. Despite equivalent reductions in mean arterial pressure (10 +/- 1 mm Hg), the increase in RSNA was significantly larger with captopril than that with nicardipine, and the plasma concentration of AVP was elevated (from 100% to 255 +/- 24%) with captopril. Mean arterial pressure was reduced, and RSNA was increased by intravenous infusion of AVP antagonist d(CH2)5Tyr(Me)AVP (n = 8), whereas vertebral artery infusion of the antagonist (n = 6) did not change RSNA. During central and peripheral infusions of AVP antagonist, RSNA was exaggerated by blood pressure reduction with nicardipine as well as with captopril. Increases in RSNA induced by captopril and nicardipine were larger by central infusion of AVP antagonist than by intravenous infusion. The decrease in mean arterial pressure by captopril (30 +/- 4 mm Hg) in eight sinoaortic-denervated hypertensive rabbits was larger than that in hypertensive rabbits with intact baroreflex. These data suggest that compensatory activation of RSNA was revealed by central and peripheral attenuation of AVP and that the sympathetic nervous system became the most important mechanism for blood pressure maintenance in the absence of AVP. The interaction of AVP with the sympathetic nervous system may be independent of the state of the renin-angiotensin system, since the exaggeration of RSNA by AVP antagonist was qualitatively the same with nicardipine as with captopril. In conscious renal-hypertensive rabbits, AVP in the central nervous system played a substantial role when blood pressure was reduced, although it did not contribute to blood pressure maintenance in the basal condition.

Angiotensin II↗
PubMed1993

Thyrotropin-producing microadenoma associated with pituitary resistance to thyroid hormone.

A 21-yr-old female with hyperthyroidism is described. Though her serum-free T3 was 17.8 pmol/L and free T4 was 60.2 pmol/L, TSH was as high as 10.7 mU/L. TRH stimulated an increase in TSH from 10.7-91.7 mU/L. T3 administration in gradually increasing doses of 100, 200, and 400 mg/day resulted in gradual reduction in serum TSH. Cranial computed tomography and magnetic resonance imaging revealed a microadenoma of the pituitary gland. Histology of the surgical specimen showed a TSH-producing adenoma with TSH cell cluster islets and decreased numbers of TSH cells in the nonneoplastic pituitary. Cultured cells from the adenoma secreted TSH spontaneously and in response to TRH. This TRH-stimulated TSH secretion was suppressed by T3 in a dose-dependent manner. One year postoperatively, neither residual tumor nor recurrence were seen by computed tomography and magnetic resonance imaging. However TSH, as well as free T3 or T4, was still high and overresponsive to TRH.

Adenoma↗
PubMed1993

Nitric oxide synthase mRNA in endothelial cells: synergistic induction by interferon-gamma, tumor necrosis factor-alpha and lipopolysaccharide and inhibition by dexamethasone.

Regulation of nitric oxide synthase mRNA by interferon-gamma, tumor necrosis factor-alpha, bacterial lipopolysaccharide (LPS) and dexamethasone in rat aortic endothelial cells was examined. The combination of interferon-gamma (100 U/ml) and tumor necrosis factor-alpha (5000 U/ml) evoked a time-dependent increase in nitric oxide synthase mRNA and nitrite/nitrate production, both of which were inhibited by dexamethasone. Neither interferon-gamma (100 U/ml), tumor necrosis factor-alpha (5000 U/ml) nor LPS (100 ng/ml) alone was capable of increasing nitric oxide synthase mRNA and nitrite/nitrate production in these cells. However, combinations of two of the three agents synergistically increased both nitric oxide synthase mRNA and nitrite/nitrate production. When the three agents were applied simultaneously, nitric oxide synthase mRNA and nitrite/nitrate production were both markedly increased. LPS contamination, which may affect the induction of nitric oxide synthase, was below 20 pg/ml in all experiments unless LPS was added exogenously, namely, the effects observed were those of the cytokines themselves. Our results suggest that in endothelial cells, these cytokines regulate the production of nitric oxide at the level of nitric oxide synthase mRNA induction.

Amino Acid Oxidoreductases↗
PubMed1993

Dexamethasone inhibits nitric oxide synthase mRNA induction by interleukin-1 alpha and tumor necrosis factor-alpha in vascular smooth muscle cells.

The effects of interleukin-1 alpha, tumor necrosis factor-alpha and dexamethasone on the induction of nitric oxide synthase mRNA in rat aortic smooth muscle cells were studied. Neither interleukin-1 alpha (up to 100 U/ml) nor tumor necrosis factor-alpha (up to 5000 U/ml) was capable of inducing nitrite/nitrate production and nitric oxide synthase mRNA in smooth muscle cells. In contrast, treatment for 12 hr or longer with a combination of the two synergistically induced nitrite/nitrate and cyclic GMP production in cell culture media and nitric oxide synthase mRNA, both of which were prevented by dexamethasone. Contamination with bacterial lipopolysaccharide, which may affect the induction of nitric oxide synthase, was below 30 pg/ml in all experiments. Our findings show that dexamethasone and these cytokines regulate the induction of nitric oxide synthase at the mRNA level in vascular smooth muscle cells.

Amino Acid Oxidoreductases↗
PubMed1993

Effects of large and small transections of the preoptic-hypothalamic region on hydromineral regulation in rats.

To further elucidate the role of the preoptic-hypothalamic region in fluid and electrolyte balance we studied the effect of surgical preoptic-hypothalamic disconnection using either a large (preoptic-hypothalamic disconnection) or a small (medial preoptic-hypothalamic disconnection) microknife. Both the large and small cuts seemed to transect the posterior projection originating in the periventricular tissue surrounding the anteroventral third ventricle (AV3V) and extending to supraoptic nucleus, but the supraoptic-neurohypophysial pathway was severed only by the large cut. Seven-day metabolic studies showed a disruption in hydromineral balance only in large cut rats; they had increased water intake and urine volume on day 1, a near-recovery of function on days 2 and 3, and polydipsia and polyuria on days 4 to 7. There was no difference between small cut rats and sham-operated rats in metabolic measurements. The large cut rats also had sustained hypernatremia and hyperosmolality, which was enhanced after water restriction for 48 h but was not accompanied by an increase in plasma arginine vasopressin. Our data therefore suggest that the efferent fibers running caudally from the AV3V are not involved in mediation of the hydromineral regulation of the AV3V.

Animals↗
PubMed1993

A case of aldosterone producing adenoma associated with high PRA after long-term angiotensin converting enzyme inhibitor treatment.

A 62-year-old patient with non-insulin dependent diabetes (NIDDM) was admitted to our hospital for blood pressure control. He had been treated with angiotensin converting enzyme inhibitor (ACEI) for 7 years and showed marked hypokalemia with increased urinary potassium excretion. Hormonal examination revealed a normal plasma aldosterone concentration and increased plasma renin activity (PRA, 13.4 ng/ml/h), so potassium losing nephropathy was suspected. After discontinuation of the ACEI, PRA decreased to normal. An adrenal adenoma was found on abdominal magnetic resonance imaging (MRI) and adrenalectomy was performed to confirm aldosterone producing adenoma (APA). Although ACEIs are said not to alter PRA in APA, this drug was primarily responsible for the increased PRA in this case. This is a rare case of APA, which showed markedly increased PRA during ACEI treatment.

Adenoma↗
PubMed1993

Significance of steroidogenic enzymes in the pathogenesis of adrenal tumour.

We examined both activities and amounts of steroidogenic cytochrome P-450s at the posttranslational protein level and steroid contents in the adrenocortical adenoma from patients with primary aldosteronism and Cushing's syndrome. Aldosterone synthase cytochrome P-450 (human P-450aldo) was detected in the tumour portion of aldosterone-producing adenoma, but not in the normal control adrenals, at the protein level. Neither the activities nor the amounts of other P-450s in the tumour portion of aldosterone-producing adenoma were significantly different from those in the non-tumour portion in the adenoma and the normal control adrenals. The aldosterone content was significantly elevated, while the androstenedione content was significantly decreased in the tumour portion of the adenoma compared with that in the normal control adrenals. In Cushing's syndrome, both the activities and amounts of P-450(17 alpha) and P-450c21 were significantly elevated in the tumour portion compared with the non-tumour portion of the adenoma and the normal control adrenals, while those of P-450scc and P-450(11 beta) in the tumour portion were not significantly different from the normal control adrenals. The cortisol content was significantly elevated, while the amounts of aldosterone and 18-hydroxydeoxycorticosterone in the tumour portion of the adenoma were significantly decreased compared with those in the normal control adrenals. These results demonstrate that overexpression of P-450aldo in aldosterone-producing adenoma, and those of P-450(17 alpha) and P-450c21 in cortisol-producing adenoma may play some role in the pathogenesis of primary aldosteronism and Cushing's syndrome, respectively.

Adenoma↗
PubMed1993

Effects of beta-blocking agents on the release of various enzymes in muscular tissues.

We examined the kinetics study of serum enzyme after the administration of beta-blocking agents or alpha-stimulator in the experimental rats. Following the administration of beta-blocking agents, propranolol and pindolol, the serum levels of adenylate kinase, aldolase, lactate dehydrogenase and aspartate aminotransferase as well as that of creatine kinase increased in rats. The same was observed following the administration of noradrenaline (an alpha-stimulator). Isoenzyme pattern indicated that most of these enzymes were considered to be released from muscular tissues. There were also changes in serum calcium, inorganic phosphorus and magnesium, concurrently with the release of the enzymes into the serum.

Adrenergic beta-Antagonists↗
PubMed1993

Effects of sodium and chloride ions on blood pressure in deoxycorticosterone acetate-treated rats.

The effects of sodium (Na+) and chloride ions (Cl-) on blood pressure were studied in rats treated with deoxycorticosterone acetate (DOCA). Four groups were prepared, each consisting of male Wistar rats that underwent heminephrectomy and administration of DOCA: the control group was maintained with tap water, the NaCl group with tap water containing 1% sodium chloride, the NaCit group with tap water containing 1.67% sodium citrate (including an equivalent dose of Na+ to 1% NaCl), and the ChoCl group with tap water containing 1.15% choline chloride (including an equivalent dose of Cl- to 1% NaCl). The time-course of systolic blood pressure showed only slight change in blood pressure in the control and ChoCl groups, and in the NaCl and NaCit groups. The rotational correlation time, an index of the fluidity of erythrocyte membrane, with spin-labeling of 16-doxyl-stearic acid, was significantly (p < 0.05) higher in the NaCl and NaCit groups than in the control group, indicating an increase in the membrane fluidity, i.e., membrane fragility. The sodium, potassium ions-activated adenosine triphosphatase (Na+,K(+)-ATPase) activity of the erythrocyte membrane was decreased to 22% (P < 0.01) and 24% (P < 0.01) in the NaCl and NaCit groups, respectively, compared with the control groups; this activity was decreased to 43% in the ChoCl group (P < 0.05). The Ca(2+)-ATPase activity showed similar changes. In contrast, there were no marked differences in the erythrocyte electrolyte level between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Glucose-induced insulin secretion and alpha 2-adrenergic receptor subtypes.

alpha 2-Adrenoceptor antagonists have been investigated in human in vivo studies as new oral antihyperglycemic agents. alpha 2-Adrenoceptors are subdivided into alpha 2A and alpha 2B subtypes by using receptor-binding methods or cloning methods. This study was designed to determine the alpha 2-adrenergic receptor subtype(s) involved in glucose-induced insulin and glucagon secretion from the isolated perfused rat pancreas at a glucose concentration of 16.7 mmol/L. Both the alpha 2A-preferential agonist oxymetazoline and the non-subtype-selective alpha 2-agonist p-aminoclonidine, at concentrations above 10(-9) mol/L, significantly inhibited glucose-induced insulin secretion (p < 0.05 and p < 0.01, respectively) and stimulated glucagon secretion from 10(-7) mol/L, as compared with basal levels (p < 0.01, respectively). In contrast, the alpha 1-selective agonist phenylephrine, at concentrations up to 10(-6) mol/L, affected neither insulin nor glucagon secretion as compared with basal levels. Furthermore, the non-subtype-selective alpha 2-antagonist rauwolscine, at concentrations above 10(-6) mol/L, and the alpha 2A-preferential antagonist WB-4101, at 10(-5) mol/L, significantly antagonized the effects of 10(-7) mol/L p-aminoclonidine on both insulin and glucagon secretion (p < 0.01 and p < 0.05, respectively). In contrast, neither the alpha 1- and alpha 2B-selective antagonist prazosin nor the alpha 2B-preferential antagonist chlorpromazine, at concentrations up to 10(-5) mol/L, antagonized the effects of p-aminoclonidine. These results suggest that alpha 2A rather than alpha 2B-adrenergic agonism inhibits glucose-induced insulin secretion and stimulates glucagon secretion in the isolated perfused rat pancreas.

Adrenergic alpha-Agonists↗
PubMed1993

Isoproterenol stimulates Cl- current by a Gs protein-mediated process in beta-intercalated cells isolated from rabbit kidney.

To examine the effect of isoproterenol on Cl- current and its signal transduction pathway in beta-intercalated cells (beta-IC cell), peanut agglutinin (PNA) positive cells in culture were studied by the whole-cell clamp technique. We identified these cells as beta-IC cells by PNA-binding, cell alkalinization induced by Cl- free in the superfusate, and an increase in intracellular cAMP concentration by isoproterenol, but not by vasopressin. Application of isoproterenol in the voltage-clamp mode induced an activation of Cl- current in a dose-dependent fashion and its threshold concentration was in the order of 0.01 microM and ED50 was about 0.1 microM. This effect of isoproterenol was inhibited by atenolol, a beta-adrenergic blocker. Either extracellular application of forskolin or intracellular application of cAMP mimicked the action of isoproterenol. In the presence of forskolin or cAMP, isoproterenol caused little further activation of Cl- current. A synthetic inhibitor of protein kinase A (5-24 amide) inhibited the Cl- -channel activation by isoproterenol. Isoproterenol failed to activate the current in the presence of intracellular GDP beta S. By contrast, intracellular application of GTP gamma S rendered irreversible the Cl- -channel activation by brief exposure to isoproterenol. The present studies provide direct evidence that in the PNA-binding cell, probably the beta-IC cell, the stimulation of beta-adrenoceptor activates Cl- current through the signal transduction system involving G-protein, adenylate cyclase, cAMP, and protein kinase A.

Animals↗
PubMed1993

Effects of magnesium on the renin-angiotensin-aldosterone system in human subjects.

Recent prospective study of intravenous magnesium sulphate administration into patients with acute myocardial infarction revealed the improvement of survival rate of these patients. This study was designed to determine the effect of intravenous administration of magnesium on the renin-angiotensin-aldosterone (RAA) system. MgSO4 (0.72% in 3.24% glucose solution) at 5 mEq/hr was infused intravenously into six healthy normotensive men for six hours. MgSO4 infusion increased plasma renin activity (PRA) at 60 minutes (4.1 +/- 1.4 ng/ml/hr vs 2.7 +/- 0.8 ng/ml/hr, p < 0.05) and decreased plasma aldosterone concentration (PAC) at 180 minutes (40 +/- 8 pg/ml vs 60 +/- 12 pg/ml, p < 0.05). The maximum level of serum magnesium reached 2.32 +/- 0.09 mEq/L, from the control value of 1.58 +/- 0.07 mEq/L, at -3 hours. Analysis of both serum levels and urinary excretion of electrolytes revealed significant increases in urinary excretion of calcium and magnesium, whereas no significant changes in other electrolytes in serum or urinary excretion were found. To clarify the mechanism by which magnesium increased PRA and suppressed PAC, either prostaglandin synthesis inhibitor, indomethacin (75 mg/day), or a calcium channel blocker, diltiazem (90 mg/day), was administered. Indomethacin completely blocked the increase in PRA but did not induce any changes in PAC. Diltiazem inhibited the decrease in PAC but did not induce any changes in PRA. These data indicate that magnesium stimulates renin release through the elevation of prostaglandins and suppresses aldosterone production through the intracellular calcium mobilization. From these results it is suggested that a favorable effect of magnesium administration to patients with myocardial infarction relates to the alterations of the RAA system.

Adult↗