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Biomedical subjects

T Takabatake

Publications and source records attributed to T Takabatake.

At least 73 records · Page 4Linked to original sources

Effects of endothelin on renal hemodynamics and tubuloglomerular feedback.

The effect of endothelin (ET)-1 infusion on renal hemodynamics and the tubuloglomerular feedback (TGF) mechanism was examined in rats. ET-1 reduced early proximal flow rate (EPFR) measured in the absence of distal flow from 28 +/- 1 to 23 +/- 1 nl/min at a subpressor dose (100 pmol.100 g body wt-1.h-1 iv) and from 27 +/- 2 to 19 +/- 2 nl/min at a pressor dose (200 pmol.100 g body wt-1.h-1). Reductions of EPFR induced by loop perfusion at 40 nl/min were 11 +/- 1 and 12 +/- 1 nl/min at the subpressor and pressor doses and were not different from controls. The stop-flow pressure response to loop perfusion was not altered by the pressor dose of ET-1. The subpressor dose of ET-1 increased renal vascular resistance (RVR) by 40% but left glomerular filtration rate (GFR) and urinary excretion of sodium (UNaV) unaltered. The pressor dose of ET-1 not only increased RVR by 140% and decreased GFR and renal plasma flow by 37 and 52%, but it increased UNaV proportional to the rise in blood pressure (r = 0.724, P less than 0.01). ET-1 is a potent renal vasoconstrictor and induces pressure natriuresis. ET-1 increases both pre- and postglomerular resistances but does not affect TGF response.

Animals↗

Intraglomerular expression of MHC class II and Ki-67 antigens and serum gamma-interferon levels in IgA nephropathy.

In order to clarify intraglomerular cellular activation and cytokine involvement in IgA nephropathy, the glomerular expression of MHC class II antigens (HLA-DR and DQ) and cellular proliferative nuclear antigen (Ki-67), and serum gamma-interferon (gamma-IFN) levels were evaluated in 49 patients with IgA nephropathy. HLA-DR was detected in all but 4 patients in whom glomerular sclerosis was present. HLA-DQ and Ki-67 were observed in 51 and 38% of the patients, respectively. Proteinuria, recent macroscopic hematuria, mesangial proliferation, and extracapillary and endocapillary lesions were more frequent and more severe in HLA-DQ-positive than in HLA-DQ-negative patients. In 10 patients with acute exacerbation, endocapillary lesions and HLA-DQ and Ki-67 expression were present in 70, 80 and 88%, respectively. Serum gamma-IFN levels were high in the patients (2.0 +/- 0.3 U/ml, n = 40), especially during acute exacerbation (3.4 +/- 1.1 U/ml, n = 9). Glomerular HLA-DO and Ki-67 expression correlated with serum gamma-IFN levels (r = 0.73, p less than 0.01 for HLA-DQ; r = 0.75, p less than 0.01 for Ki-67). Renal biopsy specimens taken before and after prednisolone and/or urokinase therapy were available from 4 patients. There was strong reactivity to HLA-DQ in the glomerular tufts of all 4 pretreatment samples. However, HLA-DQ reactivity disappeared after treatment in 3 samples, concomitant with normalization of serum gamma-IFN levels. We conclude that serum gamma-IFN levels are related to glomerular HLA-DQ and Ki-67 expression and acute exacerbation in patients with IgA nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Bacteriostatic effect of 4,7-dicyanobenzofurazan due to inactivation of 2,3-dihydroxyisovalerate dehydratase.

As part of our research on benzofurazans (BZs), we have reported the bacterioses of BZs in Escherichia coli, which may be due to O2-. produced within E. coli in the presence of dioxygen (O2). Incubation of E. coli with 4,7-dicyanobenzofurazan (1) lowered the 2,3-dihydroxyisovalerate dehydratase activity detectable in extracts from these cells. Addition of branched chain amino acids such as valine and leucine protected E. coli from growth inhibition by compound 1, though it could not protect E. coli from the damage by paraquat (PQ). Addition of Fe(III)-tris[N-(2-pyridylmethyl)-2-aminoethyl]amine (Fe-TPAA), a novel superoxide dismutase mimic, protected the dehydratase in a dose-dependent manner, which confirms that inactivation of the dehydratase is largely due to production of O2-.. The possibility was discussed that the bacteriostatic effect of compound 1 is due to the inactivation of 2,3-dihydroxyisovalerate dehydratase.

Bacteria↗

[Renal adaptations to acid-base disorders].

Alterations in acid-base status affect renal hemodynamics and tubular function. GFR is reduced both in acute acidosis and alkalosis. Tubular functional adaptation to acute acidosis includes an acceleration in proximal acidification, induced by the increase in Pco2 and luminal bicarbonate concentration and a stimulated ammonia production, induced by low pH. Alteration in distal bicarbonate reabsorption is also an important determinant of the net acid excretion. Renal functional alterations in acute alkalosis include a reduction in GFR and a stimulated bicarbonate secretion in the cortical collecting duct. Proximal acidification is almost unchanged during acute alkalosis but reportedly accelerates after at least 3 weeks of maintained alkalosis. Renal adaptation during chronic phase of acid-base disorders differs from that during the acute phase.

Acidosis↗

Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction.

The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 l.kg-1, the absorption rate constant was 2.2 h-1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml.min-1.1.48 m-2). Dosage adjustment of SUN 1165 is necessary in renal failure.

Acute Kidney Injury↗

Blood pressure and tubuloglomerular feedback mechanism in chronically salt-loaded spontaneously hypertensive rats.

Experiments were performed to qualitatively characterize the effects of tubuloglomerular feedback (TGF) inhibition by chronic salt loading on salt sensitivity of blood pressure in spontaneously hypertensive rats (SHR). After two weeks of salt loading, systolic blood pressure (SBP) was significantly exacerbated and plasma volume (PV) was expanded in salt-loaded SHR compared with those in control SHR (SBP: 182 +/- 1 vs. 159 +/- 2 mm Hg; PV: 4.38 +/- 0.06 vs. 4.04 +/- 0.03 ml/100 g body wt, respectively). Plasma volume of WKY was also but only transiently expanded by salt loading, whereas plasma volume expansion in SHR had persisted over the entire dietary treatment period. TGF activity was assessed as the maximal reduction of single nephron GFR (SNGFR) on increasing loop of Henle perfusion rate from 0 to 40 nl/min using previously collected tubular fluid from salt-loaded rats (TFs) or control rats (TFc). Maximal TGF response in salt-loaded SHR with TFs was 14.9 +/- 2.9% and 57.8 +/- 2.6% with TFc. In control SHR the responses were 16.9 +/- 2.5% with TFs and 52.7 +/- 2.9% with TFc. In salt-loaded WKY the response with TFs were 3.1 +/- 1.6% and 37.4 +/- 2.8% with TFc. And in control WKY, the response with TFs were 8.2 +/- 1.9% and 40.8 +/- 2.8% with TFc, respectively. These results indicate the TGF resetting in chronically salt-loaded SHR and WKY is caused by the activation of humoral TGF inhibitory factor. The suppression of TGF in SHR was, however, far more variable and, on average, less than in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Formation of superoxide by benzofurazans in Escherichia coli under aerobic incubation.

The superoxide (O2-.) production in Escherichia coli through the action of benzofurazans (BZs) was examined using the cytochrome c (cyt. c) reduction method. Adding BZs to E. coli cell suspensions caused the cyt. c reduction, which was completely inhibited by superoxide dismutase (SOD). The effects of BZs on cyt. c reduction was in the order of benzofurazan (1) approximately 4,7-dimethylbenzofurazan (2) approximately 4,7-dibromobenzofurazan (3) less than 4-bromo-6-cyanobenzofurazan (4) less than 4,7-dicyanobenzofurazan (5). This was correlated with the toxicity of BZs against E. coli growth (1 approximately 2 approximately 3 less than 4 less than 5) and with the redox potentials of BZs (1 approximately 2 less than 3 less than 4 less than 5). The formation of compound 5 anion radical in the cell suspensions in the absence of dioxygen (O2), was determined using ESR spectrum. The ESR signal of the anion radical disappeared with the addition of O2. The BZs effected the O2-. production in E. coli cells.

Aerobiosis↗

Endothelin effects on renal function and tubuloglomerular feedback.

Analysis of our data in conjunction with other recent literature allows the following conclusions regarding the role of endothelin in the tubuloglomerular feedback control mechanism and in the pathogenesis of acute ischemic renal failure: (1) Endothelin reduces nephron filtration rate in the nephrons with interrupted signal perception at the macula densa, in accord with preglomerular arteriolar constriction. Yet, the increase in filtration fraction in the whole kidney clearance study suggests a preferential postglomerular arteriolar constriction. Taken together, endothelin, which is a very potent renal vasoconstrictor, seems to constrict both preglomerular and postglomerular arterioles with a predominant constriction of the latter at the doses employed. (2) The endothelin-induced natriuresis is due to a fall in tubular reabsorption, reflecting a direct tubular action, possibly related to an elevation in blood pressure. (3) At the doses of endothelin used and under the present experimental conditions, changes in the magnitude of tubuloglomerular feedback (TGF) response or the feedback characteristic could not be detected. (4) No evidence was found for a participation of endothelin in the pathogenesis of acute postischemic renal failure, as evidenced by the absence of an improvement in glomerular filtration after treatment with endothelin antiserum.

Animals↗

Effect of atenolol or enalapril on diurnal changes of blood pressure in Japanese mild to moderate hypertensives: a double-blind, randomised, crossover trial.

This randomised, double-blind, crossover study compared enalapril 5 mg, and atenolol 50 mg, each dosed once daily for 4 weeks, and investigated casual and diurnal BP changes using 24 hour ambulatory BP monitoring. Both atenolol and enalapril satisfactorily lowered BP during the day and no excessive falls occurred at night. The tendency for BP to increase during the day and decrease at night was maintained during both active periods. Pulse rate was reduced only by atenolol throughout 24 hours. The BP increase observed 2 hours after rising in the morning was suppressed by atenolol but not by enalapril. Both drugs reduced the rates of systolic (greater than or equal to 160 mmHg) and diastolic (greater than or equal to 95 mmHg) BP increases to half of those during placebo. The frequency with which diastolic BP increased above these limits was less during the atenolol period. The difference in BP between a hospital casual reading and the mean 24 hour ambulatory reading was reduced only by atenolol. Furthermore, only atenolol suppressed the BP and pulse rate increases on exercise.

Adult↗

Attenuation of enhanced tubuloglomerular feedback activity in SHR by renal denervation.

We evaluated the effect of acute unilateral renal denervation (DNX) on the tubuloglomerular feedback (TGF) mechanism in Inactin-anesthetized hydropenic male 8- to 10-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). SHR had higher mean arterial pressure (MAP, 28%) and renal vascular resistance (RVR, 35%), whereas renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, and sodium excretion were similar. DNX in SHR did not change MAP but decreased RVR (26%) and increased RBF (29%), GFR (16%), urine flow (52%), and sodium excretion (431%). DNX did not affect these in WKY. Loop of Henle perfusion with Ringer solution reduced early proximal flow rate (EPFR) in SHR more than in WKY; significantly different at a loop flow of 20 nl/min (9.8 +/- 0.7 vs. 6.5 +/- 0.7 nl/min). DNX in SHR increased the nonperfused EPFR from 25.6 +/- 1.1 to 31.7 +/- 1.3 nl/min and reduced TGF responses during perfusion at both 20 nl/min (9.8 +/- 0.7 vs. 4.4 +/- 0.7 nl/min) and 40 nl/min (14.2 +/- 1.1 vs. 10.4 +/- 0.7 nl/min). TGF sensitivity was attenuated by DNX, as indicated by reduced maximum reactivity (-0.89 +/- 0.14 to -0.36 +/- 0.07) and increased turning point (16.5 +/- 0.9 to 25.2 +/- 2.9 nl/min). TGF responses in WKY were not influenced by DNX. Sham denervation did not alter renal hemodynamics and TGF. These results indicate that renal nerves exert a tonic influence on the renal vasculature and the TGF system in SHR but not in WKY. Enhanced TGF responsiveness may be involved in volume retention and in the maintenance of hypertension in SHR.

Animals↗

Toxicities of dicyanobenzofurazans with formation of superoxide in Escherichia coli.

The toxicities of some benzofurazans (BZs), benzofurazan (1), 4,7-dimethylbenzofurazan (2), 4,7-dibromobenzofurazan (3), 4-bromo-6-cyanobenzofurazan (4), 4,7-dicyanobenzofurazan (5) and 4,5-dicyanobenzofurazan (6), were examined on Escherichia coli. Compound 5 at 4 microM and compound 6 at 7 microM completely inhibited the growth of E. coli in a simple nutritionally restricted medium (GM medium). These compounds were more toxic in GM medium than in a nutritionally rich medium (YE medium), which contained yeast extract as an additive in GM medium. Compound 4 also inhibited the growth of E. coli at 300 microM in GM medium. The toxicities of BZs were in the order of 1 approximately 2 approximately 3 less than 4 approximately 5 approximately 6. Compounds 4, 5 and 6 induced manganese-superoxide dismutase (Mn-SOD) and catalase activities of E. coli in YE medium. The induced SOD and catalase provide a defense against the potential cytotoxicities of O2- and H2O2. The rate of dioxygen uptake in cyanide-resistant respiration of E. coli was dependent on the concentration of 5, and was correlated with the induction of SOD and catalase. The reduction potentials of BZs followed the order of 1 approximately 2 less than 3 less than 4 less than 5 approximately 6. Compounds 5 and 6, which had redox potentials higher than those of the other BZs, are thought to be more readily reduced in the living system.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzoxazoles↗

Sensitivity of arterial baroreflex changes during daily activity.

1. Continuous ambulatory arterial pressure monitoring was performed by telemetry in 34 hypertensive and four normotensive subjects and arterial baroreflex sensitivity was evaluated by computer analysis of pulse wave. Three consecutive pulses were selected, on two criteria, from the 24 h recording: (i) progressive and linear increase or decrease in systolic arterial pressure and heart period, (ii) change of systolic arterial pressure in three pulses exceeds a threshold value. The systolic arterial pressure and heart period of three pulses were averaged and the slopes of systolic arterial pressure and heart period were calculated as baroreflex sensitivity. 2. When the threshold value was set to 5 mmHg, baroreflex sensitivity measured by the present method correlated with baroreflex sensitivity as measured by the phenylephrine method (r = 0.667, P less than 0.001). 3. The baroreflex sensitivity from the pressor-bradycardia and the depressor-tachycardia reflex decreased as threshold value was increased from 3 to 4 mmHg to over 20 mmHg. With the pressor-bradycardia reflex, the initial systolic arterial pressure of three pulses did not change, but the initial heart period shortened progressively as the threshold increased. With the depressor-tachycardia reflex, the initial systolic arterial pressure increased and the initial heart period shortened progressively. This suggests that the sensitivity of arterial baroreflex changes dynamically according to input of reflex are during daily activity.

Adult↗