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Biomedical subjects

T Takabatake

Publications and source records attributed to T Takabatake.

At least 55 records · Page 3Linked to original sources
PubMed1995

Direct effects of angiotensin I, angiotensin II, an ACE inhibitor and a serine proteinase inhibitor on cultured heart cells from spontaneously hypertensive rats.

1. The purpose of the present study was to investigate how angiotensin I (AI), angiotensin II (AII), an angiotensin converting enzyme inhibitor (ACE inhibitor; ACE-I) and a serine proteinase inhibitor contribute to the protein metabolism of cultured newborn spontaneously hypertensive rats (SHR) heart cells. We examined the uptake of [3H]-uridine and [3H]-proline into cultured cardiac myocytes and fibroblasts, respectively. 2. Both AI and AII increased the uptake of [3H]-uridine into myocytes in a concentration-dependent manner. However, the effect of AI was denied in the presence of the ACE-I with the concentration of 10(-6) g/mL. Both AI and AII increased the uptake of [3H]-proline into cardiac fibroblasts in a concentration-dependent manner. However, this effect was only partially abolished in the presence of 10(-6) g/mL of the ACE-I, which was the maximal concentration that did not exert any effect on the [3H]-proline uptake. In the presence of AII receptor antagonist, [Sar1, Leu8]-AII, the uptake of [3H]-proline into cardiac fibroblasts was completely inhibited. Moreover, the stimulatory effects of AI on the uptake of [3H]-proline into cardiac fibroblasts were completely inhibited in the presence of a serine proteinase inhibitor in addition to the ACE-I. 3. These results suggest that an ACE-I has different effects on protein metabolism in the heart and also suggest the presence of serine proteinase in cultured cardiac fibroblasts from SHR.

Angiotensin I↗
PubMed1995

[Microcirculation in renal interstitium].

Microcirculation in the renal interstitium plays an important role in the regulation of urinary sodium excretion and thus in the control of blood pressure. An increase in renal interstitial hydrostatic pressure caused by renal perfusion pressure elevation induces pressure natriuresis by decreasing tubular reabsorption. Chronic NO inhibition in the medullary interstitium decreases medullary blood flow and induces sodium retention and blood pressure elevation. Chronic medullary, but not intravenous, infusion of ACE inhibitor restores the impaired pressure natriuresis by improving medullary microcirculation in SHR. The tubuloglomerular feedback signal transmission is dependent on Cl concentration in the juxtaglomerular interstitium and its sensitivity is modulated by pressure there in.

Animals↗
PubMed1994

Contrasting effects of isoproterenol and phosphodiesterase III inhibitor on intracellular calcium transients in cardiac myocytes from failing hearts.

1. Effects of a newly developed phosphodiesterase (PDE) III inhibitor, E-1020, on intracellular calcium transients were compared with those of isoproterenol (ISO) in isolated single myocytes from failing hearts secondary to pulmonary hypertension induced by monocrotaline injection. Myocytes were isolated by enzyme digestion using a Langendorff apparatus. Changes in intracellular calcium concentrations ([Ca2+]i) were recorded using a fura-2 fluorescence microscopic technique. Cyclic AMP contents of the hearts were measured by radio-immunoassay. 2. Myocytes from failing hearts showed Ca2+ transients with a low peak (low amplitude) and delayed decline of Ca2+ transients. Both ISO and E-1020 increased peak [Ca2+]i, max + d[Ca2+]i/dt, and max - d[Ca2+]i/dt in a concentration-dependent manner while both agents decreased T80L (time to 80% decline of amplitude from peak light). The concentrations which increased peak [Ca2+]i by 50% were 1.6 x 10(-9) mol/L of ISO and 2 x 10(-6) mol/L of E-1020. These concentrations increased cAMP in the heart to the same levels. Analysis of the effects of both agents on peak [Ca2+]i versus max - d[Ca2+]i/dt showed that ISO is much more effective on peak [Ca2+]i while E-1020 is more effective on max - d[Ca2+]i/dt. 3. These results showed that the effects of ISO and E-1020 on the parameters of intracellular Ca2+ transients of single myocytes from failing hearts are slightly different, and suggest that E-1020 may improve diastolic function as well as systolic function in failing hearts.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Effects of an angiotensin II receptor antagonist, TCV-116, on renal haemodynamics in essential hypertension.

The renal effects of a nonpeptide angiotensin II receptor antagonist, TCV-116, were investigated in 12 hospitalised patients with mild-to-moderate essential hypertension. After a 2-week placebo period, TCV-116 was given for 2 weeks in increasing doses from 4 mg to 8 mg daily to normalise the mean blood pressure. Blood pressure fell from 156 +/- 9/93 +/- 3 mmHg at the end of the placebo period to 140 +/- 9/85 +/- 4 mmHg after TCV-116 treatment. The pulse rate was unchanged. Renal vascular resistance fell from 1.62 +/- 0.20 to 1.37 +/- 0.17 dyne.s.cm-5 . 1.48 m2 x 10(4), renal plasma flow increased from 329 +/- 19 to 367 +/- 27 mL.min-1.1.48 m-2, and GFR was unchanged despite a fall in renal perfusion pressure. TCV-116 reduced the filtration fraction from 0.302 +/- 0.019 to 0.258 +/- 0.009, suggesting a preferential reduction in efferent arteriolar resistance. The fractional excretion of sodium, potassium, and urate did not change. An increase in plasma renin activity (from 1.1 +/- 0.3 to 2.2 +/- 0.7 ng.mL-1.h-1) and a fall in the plasma aldosterone concentration (from 6.2 +/- 0.8 to 4.5 +/- 0.7 ng.dL-1) were also seen. These results indicate that TCV-116 has favourable renal effects and a concomitant hypotensive action in patients with mild-to-moderate essential hypertension.

Adult↗
PubMed1993

Renal effects of manidipine hydrochloride. A new calcium antagonist in hypertensive patients.

The renal effects of manidipine hydrochloride were investigated in ten hospitalised patients with mild-to-moderate essential hypertension. After a one-week placebo period, manidipine was given for 1 week in a dose rising from 5 mg to 10 mg or 20 mg daily to normalise the mean blood pressure measured after 2 h. Blood pressure had decreased from 171/101 to 147/86 mm Hg at the end of manidipine treatment. The pulse rate was unaltered. Renal vascular resistance decreased from 1.90 to 1.33 dyn.s.cm-5/1.48 m2 x 10(4), and renal blood flow and glomerular filtration rate increased from 522 to 662 ml.min-1 x 1.48 m-2 and from 81 to 93 ml.min-1 x 1.48 m-2, respectively, in spite of a fall in renal perfusion pressure. Manidipine reduced the filtration fraction from 0.260 to 0.243, suggesting a preferential reduction in efferent arteriolar resistance. The fractional excretion of sodium and potassium did not change. Manidipine did not produce any significant alteration in plasma renin activity or in the plasma aldosterone concentration. The results indicate that manidipine has favourable renal effects and a concomitant hypotensive action in patients with mild-to-moderate essential hypertension.

Adult↗
PubMed1993

Effect of calcium antagonist, manidipine hydrochloride, on renal hemodynamics and tubuloglomerular feedback in spontaneously hypertensive rats.

The effects of a calcium antagonist, manidipine, on renal hemodynamics and the tubuloglomerular feedback (TGF) mechanism were examined in 7- to 8-week-old spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar-Kyoto rats (WKYs). Manidipine, 10 micrograms/kg intravenously, reduced blood pressure only in SHRs. A greater increase in renal plasma flow occurred in SHRs, but effects on GFR were observed in both SHR and WKY rats. Filtration fraction decreased only in SHRs. The TGF response curve in SHRs was shifted to the left compared with that in WKY rats, indicating a more active TGF in hypertensive rats. Manidipine infusion produced a right and upward shift of the feedback curve in SHRs and only an upward shift in WKY rats. We conclude that manidipine corrects hyperactivity of the TGF mechanism in SHRs.

Animals↗
PubMed1993

[Risk factors for contrast nephropathy in diabetic patients undergoing cardioangiography].

Risk factors for contrast nephropathy were prospectively studied in 17 patients with non-insulin dependent diabetes mellitus undergoing cardioangiography. Contrast nephropathy, defined as a serum creatinine increase of greater than 25% at 3 day after angiography, occurred in 29.4% of diabetic patients. Patients who developed contrast nephropathy had significantly higher serum creatinine (Cr), fractional excretion of sodium (FENa), urinary albumin excretion rate (AER), and lower 24hr Ccr than patients who did not (Cr: 1.5 +/- 0.3 mg/dl vs. 0.8 +/- 0.1 mg/dl, FENa: 1.9 +/- 0.5% vs. 0.6 +/- 0.1%, AER: 522 +/- 335 micrograms/min vs. 27 +/- 13 micrograms/min, 24hr Ccr: 39.1 +/- 11.6 ml/min vs. 86.2 +/- 9.3 ml/min, P < 0.05). Contrast nephropathy developed in all of two patients with overt proteinuria (AER more than 200 micrograms/min), but none of eight patients with normoalbuminuria (AER below 15 micrograms/min). Three of seven patients with microalbuminuria developed contrast nephropathy, and two of them had advanced nephropathy. FENa obtained next day was significantly elevated over baseline in patients with contrast nephropathy (1.9 +/- 0.5% vs. 9.7 +/- 4.5%, P < 0.05), but unchanged in patients without contrast nephropathy. The rise in C beta 2-microglobulin/Ccr and enzymuria was noted in both group. Percentage decrease of Ccr on the next day was positively correlated with FENa before angiography (r = 0.645, p < 0.01). Of 24hr Ccr, AER, and FENa before angiography, FENa was revealed as a statistically significant discriminant factor for contrast nephropathy by stepwise discriminant analysis (p = 0.0008). These results suggest that contrast nephropathy develops predominantly in the stage not of incipient but of overt diabetic nephropathy indicated by a decline of glomerular filtration, overt proteinuria, and tubular dysfunction. Of them, tubular dysfunction may be the most important risk factor for contrast nephropathy.

Aged↗
PubMed1993

[Evaluation of renal function using 99mTc-MAG3: comparison with 123I-OIH and 99mTc-DTPA].

The utility of 99mTc-mercaptoacetyltriglycine (MAG3) with studied clinically. In the renography obtained with 99mTc-MAG3, the abdominal aorta and the common iliac arteries were clearly visualized in the vascular phase. Due to less background activity and high target to background ratio, the quality of 99mTc-MAG3 image was superior to that of 123I-OIH or 99mTc-DTPA image. The parameters on the renogram including Tmax, T2/3, and T1/2 were compared. The correlation of Tmax and T2/3 or T1/2 were not significant between 99mTc-MAG3 and 123I-OIH. Another parameter of C20/Cmax, where C20 and Cmax are renal activities at 20 min after injection and at Tmax respectively, showed an excellent correlation between 99mTc-MAG3 and 123I-OIH. Using C20/Cmax, pattern of renogram can be characterized numerically. Concerning about the relation between C20/Cmax and renogram pattern, standard renogram pattern showed the C20/Cmax value of less than 0.4, while hypofunctioning pattern showed more than 0.5. The correlation coefficient between the renal uptake of 99mTc-MAG3 and 123I-OIH was 0.880 with a correlation plot: "Y = 1.16X-0.043", where X and Y represent renal uptake of 99mTc-MAG3 and 123I-OIH, respectively. It can be concluded that 99mTc-MAG3 is useful renal imaging agent as an alternative to 123I-OIH, in order to evaluate the proximal tubular function and calculate ERPF.

Adult↗
PubMed1992

Difference in superoxide toxicity between 4,7-dicyanobenzofurazan and paraquat.

The O2-. production by aerobically cultured Escherichia coli in the presence of benzofurazan (1), 4,7-dimethylbenzofurazan (2), 4,7-dibromobenzofurazan (3), 4-bromo-6-cyanobenzofurazan (4), and 4,7-dicyanobenzofurazan (5) was examined by using the cytochrome c reduction method in order to elucidate the mechanism of cytotoxicity of benzofurazans. Adding compound 5 to E. coli cell suspension caused cytochrome c reduction, which was completely inhibited by superoxide dismutase. The rate of cytochrome c reduction was in the order of 1 = 2 = 3 less than 4 less than 5, which correlates well with that of the reduction potentials of these benzofurazans. Adding glucose to the E. coli cell suspension-compound 5-cytochrome c system accelerated the rate of cytochrome c reduction. The formation of 4,7-dicyanobenzofurazan anion radical in the cell suspension-compound 5-glucose system in the absence of O2 was followed by ESR spectroscopy. The ESR signal of the anion radical disappeared when O2 was added. Compound 5 was shown to have an approximately 10-fold greater increasing effect on the flux of O2-. by E. coli than paraquat (PQ) by the cytochrome c reduction method. The results were confirmed by the electrochemical method with an oxygen electrode. However, compound 5 had a bacteriostatic, but not lethal, effect, while PQ had both effects. The effect of compound 5 and PQ on lethality of E. coli showed a dramatic difference when E. coli was exposed to these two compounds and washed prior to testing the effects of that exposure. This difference probably arose because compound 5 readily leaked from the cells during dilution and plating. Also, the reduced form of compound 5 exits from the cells more readily than the reduced form of PQ and then generates O2-. in the medium by autoxidation. This suggests the importance of the intracellular production of O2-., rather than the extracellular production of O2-., for lethal effect.

Benzoxazoles↗
PubMed1992

Effect of nicardipine on haemodynamic response to stress in hypertension.

The effects of the calcium antagonist nicardipine on the pressor response to mental arithmetic, cold pressor and exercise tests have been studied in fifteen patients with established mild to moderate essential hypertension. Nicardipine 20 mg p.o. showed a hypotensive effect within 60 min, associated with a fall in total peripheral resistance and an increase in heart rate. As the pressor response to each stress was not affected by nicardipine, the peak blood pressure reached during each stress was lower. Nicardipine lowers blood pressure at rest as a result of arteriolar dilatation, associated with reflex tachycardia. The pressor responsiveness to various stresses was not affected by nicardipine.

Adult↗
PubMed1992

Up-regulated MHC-class II expression and gamma-IFN and soluble IL-2R in lupus nephritis.

Expression of MHC-class II molecules (HLA-DR and -DQ), serum gamma-interferon (gamma-IFN) and soluble interleukin-2 receptor (sIL-2R) levels were studied in 35 Japanese patients with lupus nephritis (LN) to clarify intraglomerular cellular activation and cytokine involvement in human LN. In 11 normal kidney specimens, HLA-DR(Ia1) was noted in glomerular tufts, but HLA-DQ was either not or was faintly detected in glomeruli by the indirect immunofluorescence technique. HLA-DR and -DQ were observed mainly on the surface of glomerular endothelial cells in 100% and 50% of 28 lupus kidney specimens except for necrotic or sclerotic lesions. HLA-DQ was expressed in a high incidence of 67%, 86% in patients with proliferative LN (WHO Class III-IV) and active lesions, respectively. Serum gamma-IFN and sIL-2R levels were 1.2 +/- 0.2 U/ml and 190 +/- 24 U/ml (mean +/- SEM; N = 30) in normal controls, and elevated in patients with proliferative LN (4.1 +/- 1.0 U/ml, 383 +/- 81 U/ml, N = 25), especially with active lesions (6.2 +/- 1.5 U/ml, 500 +/- 110 U/ml, N = 14). Overall, glomerular lesions such as HLA-DQ expression, the activity index and leukocyte infiltration correlated positively with serum gamma-IFN levels (r = 0.55; P less than 0.01 for HLA-DQ, r = 0.68; P less than 0.001 for activity index, r = 0.38; P less than 0.05 for leukocyte infiltration), but not with serum sIL-2R levels, anti-DNA antibody titers and CH50 titers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Renal effects of endogenous prostaglandin synthesis promoter ONO-3122.

The renal effects of a prostaglandin synthesis agonist, 1-iodo-3-aminomethyl-5,6,7,8-tetrahydro-2-naphthol (ONO-3122), were investigated in anesthetized rats. ONO-3122 (0.3 mg/kg + 0.3 mg.kg-1.h-1 iv) doubled the urinary excretion of the main metabolites of prostaglandin F, and induced transient increases in renal blood flow and glomerular filtration rate (GFR) with a marked, stable natriuresis. Indomethacin suppressed the natriuresis. When the diuretic fluid losses were replaced, micropuncture showed an unaltered reabsorption of sodium in the proximal tubule but reductions in the loop of Henle (86 +/- 1 vs. 76 +/- 1%) and in the more distal segments (98 +/- 1 vs. 83 +/- 3%) with comparable reductions in water reabsorption. Potassium secretion was seen in the distal and collecting tubules. Without fluid replacement, sodium reabsorption was reduced in the loop and more distal nephron but increased in the proximal tubule. Differences between proximal and distal nephron GFR were unaffected by systemic ONO-3122. Loop perfusion with ONO-3122 did not change tubuloglomerular feedback responses, which were, however, completely suppressed by furosemide. It is concluded that ONO-3122 stimulates renal prostaglandin biosynthesis, transiently dilates renal vasculature, and induces natriuresis mainly by suppressing sodium and water reabsorption in the loop of Henle and the more distal nephron. Luminal ONO-3122 does not affect the tubuloglomerular feedback.

Animals↗