[Combined use of antihypertensive agents and treatment of high blood pressure].
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Biomedical subjects
Publications and source records attributed to Y Orita.
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In our previous paper (Yanase, M. et al. (1983) Biochim. Biophys. Acta 733, 95-101) we reported that the Na+-dependent D-glucose uptake into brush-border membrane vesicles is decreased in rabbits with experimental Fanconi syndrome (induced by anhydro-4-epitetracycline). In the present paper we investigate the mechanism underlying this decrease. D-Glucose is taken up into the osmotically active space in anhydro-4-epitetracycline-treated brush-border membrane vesicles and exhibits the same distribution volume and the same degree of nonspecific binding and trapping as in control brush-border membrane vesicles. The passive permeability properties of control and anhydro-4-epitetracycline-treated brush-border membrane vesicles are shown to be the same as measured by the time-dependence of L-glucose efflux from brush-border membrane vesicles. D-Glucose flux was measured by the equilibrium exchange procedure at constant external and internal Na+ concentrations and zero potential. Kinetic analyses of Na+-dependent D-glucose flux indicate that Vmax in anhydro-4-epitetracycline-treated brush-border membrane vesicles (79.3 +/- 7.6 nmol/min per mg protein) is significantly smaller than in control brush-border membrane vesicles (141.3 +/- 9.9 nmol/min per mg protein), while the Km values in the two cases are not different from each other (22.3 +/- 0.9 and 27.4 +/- 1.8 mM, respectively). These results suggest that Na+-dependent D-glucose carriers per se are affected by anhydro-4-epitetracycline, and that this disorder is an important underlying mechanism in the decreased Na+-dependent D-glucose uptake into anhydro-4-epitetracycline-treated brush-border membrane vesicles.
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This paper presents the application of wire-guide insertion of peritoneal dialysis catheter. 30 patients who required acute peritoneal dialysis were treated using a total of 37 peritoneal catheters with the wire-guide method. The catheters were left in place as long as possible (periods totalling 644 days in all). The complication of insertion was minor bleeding with blood-tinged dialysate that tended to clear spontaneously in a few days. Leakage occurred in 17 indwelling catheters but did not occur on the days of insertion. There were 3 episodes of clinical peritonitis, so the infection rate was 1 episode every 7 patient-months. This technique is safer and simpler, i.e. the incidence of peritonitis is lower in long-term indwelling catheters, and so it will contribute to the wider and earlier utilization of peritoneal dialysis.
A hypertensive crisis associated with evidence of catecholamine release was induced following intravenous administration of 10 mg metoclopramide in a woman with pheochromocytoma and in whom the tyramine test was negative. After removal of the tumor, blood-pressure and plasma catecholamine concentrations were not influenced by the administration of metoclopramide. It is suggested that the mechanism of hypertensive crises induced by metoclopramide may not be due to a direct catecholamine releasing effect from the tumor or sympathetic nerve endings, but rather to its presynaptic dopaminergic blocking effect which would indirectly release catecholamines.
To determine factors mediating the aldosterone secretory response to orthostasis, we examined the effect of angiotensin-converting enzyme inhibition (CEI) on orthostasis in eight normal subjects and 10 normotensive patients with primary glomerulonephritis ingesting a normal sodium intake. On standing with CEI, the mean plasma aldosterone concentration (PAC) did not change [68.6 +/- 3.9 (+/- SE) and 63.4 +/- 6.9 pg/ml] in normal subjects, while PAC rose significantly from 72.3 +/- 7.5 to 129.5 +/- 13.2 pg/ml (P less than 0.001) in the glomerulonephritis patients without a concurrent rise in plasma angiotensin II, serum potassium, plasma ACTH, or mean blood pressure. There was a good correlation (r = -0.7064; P less than 0.03) between the changes in PAC and the changes in fractional sodium excretion in the patients. Pretreatment with indomethacin blunted the rise in PAC from 159.0 +/- 21.5 to 63.3 +/- 10.2 pg/ml upon standing with CEI, without a concurrent change in circulating 6-keto prostaglandin F1 alpha (from 57.7 +/- 9.5 to 56.0 +/- 11.1 pg/ml) in 4 patients. These results suggest that the aldosterone secretory response to orthostasis in patients with glomerulonephritis is dependent on factors blunted by pretreatment with indomethacin in addition to angiotensin II.
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Glomerular mesangial cells were isolated from explants of normal rat whole glomeruli according to the differential growth capacities of the cultured cells. The cultured mesangial cells comprised almost all of the grown cells on day 21 of the primary culture when the subculture could be performed. They contained abundant cytoplasmic microfilaments and actin. The contractile response to vasoactive hormone of both primarily cultured and subcultured mesangial cells was quantified as a decrease in cell surface area. The maximum decrease in surface area in response to 1 nM of angiotensin II was about 30%. This magnitude of contraction is consistent with that observed in cultured rat vascular smooth muscle cells. The mesangial cells did not phagocytose horse-radish peroxidase or sensitized sheep red blood cells, nor did they have binding capacities for Fc or C3b, while the cells derived from explanted glomerulus and probably of blood-born monocyte origin did. We conclude that the most important function of the glomerular mesangial cell is the control of glomerular blood flow and filtration by contraction.
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The effect of anhydro-4-epitetracycline on sodium gradient-dependent D-glucose transport of rabbit renal brush-border membrane vesicles was studied. The purity of isolated brush-border membrane vesicles as judged by enzyme activities was not different between normal control and anhydro-4-epitetracycline-administered rabbits. There was no difference in estimate of intravesicular volume, either. When NaCl was used for sodium gradient, the overshoot of D-glucose uptake into brush-border membrane vesicles isolated from anhydro-4-epitetracycline-treated rabbits was significantly smaller than that of normal control rabbits. In the cases of NaSCN or Na2SO4, the former was also smaller than the latter, but not significantly so. To avoid the possible effect of membrane potential on D-glucose uptake, the voltage-clamp method was applied. Even in the voltage-clamped condition, the overshoot of D-glucose uptake into vesicles from anhydro-4-epitetracycline-treated rabbits was decreased compared to that of normal rabbits. In vitro incubation of brush-border membrane vesicles with 20 mM anhydro-4-epitetracycline caused no alteration in sodium gradient-dependent D-glucose uptake. Our results demonstrate that there exists a disorder in sodium gradient-dependent D-glucose uptake of renal brush-border membrane in anhydro-4-epitetracycline-treated rabbits, and suggest that this disorder is one of the underlying mechanisms of experimental Fanconi syndrome.
The effect of the change from supine to upright position on GFR (measured by creatinine clearance) was studied in nonazotemic patients with biopsy-proven primary glomerulonephritis. Compared to healthy subjects, the fall in GFR following the postural change was significantly larger in patients with mesangial proliferation (MP) and with both MP and thickening of glomerular capillary wall (GCW), while similar in those with thickening of GCW alone, suggesting that MP, but not thickening of GCW, augments posturally induced fall in GFR. The augmented fall in GFR in patients with MP was accompanied by larger fall in GFR per unit increase in plasma renin activity than in healthy subjects, and was eliminated by angiotensin-converting enzyme inhibition. We conclude that MP augments posturally induced fall in GFR through affecting glomerular reactivity to angiotensin II.
Using two-dimensional (2-D) echocardiography we evaluated the applicability of the left ventricular (LV) short axis view combined with manual scanning technique for the detection and evaluation of aneurysms of the membranous ventricular septum (AMS). In 12 patients with angiographically proven AMS, we recorded from the left sternal border the short axis view of the left ventricle continuously displayed from the aortic to the ventricular level by tilting the transducer manually along the LV long axis plane. We then compared the detectability of AMS by this method with that by other standard fixed 2-D echocardiographic views. This method proved to be best for the detection of AMS (12/12), followed by an apical four-chamber view (10/12), a parasternal LV long axis view (8/12) and an apical two-chamber (2/12) view. For the detection of AMS and for three-dimensional evaluation of the structure of the AMS and the original orifice of ventricular septal defect the method was shown to be clinically applicable.
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The effects of furosemide on the mitochondrial electron transport system and on oxidative phosphorylation were explored. Furosemide above the concentration of 2 X 10(-3) mol/l was found to inhibit state 3 (ADP-dependent) respiration of the rat liver, renal cortex, renal medulla mitochondria. State 4 (resting) respiration was not affected by furosemide. Furosemide above the concentration of 7.5 X 10(-6) mol/l (substrate: glutamate-malate), and above 5 X 10(-6) mol/l (substrate: succinate) inhibited the respiration of rat liver mitochondria released by 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile (SF 6847). This fact exactly indicates that furosemide inhibits the electron transport system in mitochondria. Furosemide at the concentration of 4 X 10(-3) mol/l inhibited the activities of NADH cytochrome c reductase and succinate cytochrome c reductase in sonicated mitochondrial subparticles of beef heart by 78.2% and 79.2% of control, respectively.
Protein-synthetic activity in the liver and muscle of rats with chronic renal failure (CRF) of 2 weeks' duration was studied by examining RNA/DNA ratios and polysome profiles and in vitro protein synthetic activity of isolated polysomes. CRF was found to cause differential effects on protein synthesis in the liver and muscle. In the liver, CRF caused impairment of protein synthesis only in the fed condition; CRF rats maintained the same "basal" protein synthetic activity as the sham-operated control rats upon 18 hours' starvation. In the muscle, the effect of CRF was manifested only in the starved condition; CRF caused extensive disaggregation of polysomes when animals were starved. It is proposed that the muscle serves as a "reserve" protein when animals sustain a protein-catabolic state such as CRF.