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Biomedical subjects

N Urakawa

Publications and source records attributed to N Urakawa.

At least 37 records · Page 2Linked to original sources
PubMed1993

Effect of dibutyryl cyclic AMP on hemodynamics and chemical mediators in dogs with experimentally-induced endotoxic shock.

The therapeutic effect of dibutyryl cyclic AMP (DBcAMP) in endotoxic shock was evaluated, using 11 dogs with experimentally-induced endotoxic shock (5 in DBcAMP group and 6 in control group) under general anesthesia. The DBcAMP group was treated by single intravenous injection of DBcAMP (10 mg/kg) at 15 min before inoculation with endotoxin (3 mg/kg). After the inoculation of endotoxin, this group was given drip infusion of DBcAMP at a rate of 0.1 mg/kg/min over 180 min. Hemodynamic parameters and chemical mediators were measured until 360 min after endotoxin inoculation. The cardiac output and urinary volume, which were decreased in the control group, were significantly inhibited to decrease in the DBcAMP group (p < 0.01). The increases in 6-keto-PGF1 alpha and thromboxane B2, chemical mediators released in endotoxic shock, were significantly inhibited (P < 0.05 and p < 0.01, respectively). These results suggested that DBcAMP is useful for the treatment of endotoxic shock.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Changes in reticuloendothelial function in dogs with endotoxin-induced shock.

A shock model was experimentally produced by intravenous injection of a lethal dose (3 mg/kg) of endotoxin under general anesthesia induced by pentobarbital sodium using 7 beagles. The effect of this endotoxic shock on the reticuloendothelial function was investigated. The blood endotoxin concentration peaked immediately after administration and decreased subsequently. However, the value still remained on an increased level (1,051 pg/ml) even at 360 min after endotoxin treatment. The lipid emulsion test as an index of reticuloendothelial phagocytotic activity and the arterial ketone body ratio as an index of the energy charge in the liver decreased after endotoxin treatment and failed to recover during the experiment. Fibronectin, one of opsonic proteins, tended to decrease after injection of the endotoxin and was significantly (p < 0.01) low at 180 and 360 min compared with the value before injection of the endotoxin. These results suggested the depression of the reticuloendothelial function during endotoxin-induced shock.

Animals↗
PubMed1993

Evaluation of extravascular thermal volume in the lung in dogs with endotoxin-induced shock by double indicator dilution method using heat and sodium ions.

Accuracy assessment was undertaken under varying hemodynamic conditions for a lung water volume measurement device which is based on the principle of a double indicator dilution method using heat and sodium ions. Changes in extravascular thermal volume were investigated in dogs with endotoxin-induced shock. The isoproterenol- or propranolol-induced changes in hemodynamics had no effect on the measurement. This confirmed the high accuracy of this measuring method. The measurement revealed a tendency for the extravascular thermal volume to gradually increase (p < 0.05) during endotoxin shock. This confirmed the gradual progression of pulmonary edema during endotoxin shock.

Animals↗
PubMed1992

A possible mechanism of endothelium-dependent relaxation induced by pirarubicin and carbachol in rat isolated aorta.

The mechanism of endothelium-dependent relaxation induced by pirarubicin, (2''R)-4'-O-tetrahydropyranyladriamycin, THP, or carbachol was investigated in the rat isolated aorta. The relaxant effect of THP (1.5 x 10(-6)-4.5 x 10(-5) M) or carbachol (10(-8)-10(-4) M) on the aorta with endothelium was decreased by lowering Ca2+ in the medium. The relaxation induced by THP was not inhibited by pretreatment with verapamil (10(-6)-10(-5) M), and that induced by carbachol was only partially inhibited. However, on replacement of all but 20 mM Na+ with either Li+ or choline, the THP- or carbachol-induced relaxation was inhibited. Furthermore, the relaxing effect of THP or carbachol was inhibited by pretreatment with amiloride (10(-4)-3 x 10(-4) M), with ouabain (10(-4)-10(-3) M), or with K(+)-depletion. These results suggest that the THP- or carbachol-induced relaxation depending on endothelium was affected by modifying the calcium ion concentration, and that a Na(+)-Ca2+ exchange process is involved.

Amiloride↗
PubMed1992

Inhibitory effects of tiamulin on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs.

The inhibitory effect of tiamulin, an antibiotic produced by Pleurotus mutilis, on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs was studied. In the thoracic aorta, tiamulin with an IC50 of 9.7 x 10(-6) M inhibited sustained contractions induced by isosmotically added 60 mM KCl. The inhibitory effect of tiamulin on a Ca(2+)-induced contraction in a depolarized muscle was competitively antagonized by raising external Ca2+ concentration. Bay K 8644 (10(-7) M) antagonized tiamulin's inhibition of the Ca(2+)-induced contraction. Tiamulin (2 x 10(-5) M) decreased the elevated cytoplasmic Ca2+ level measured by the fura 2 AM method in the depolarized muscle. In high K(+)-isoprenaline-treated left atria, tiamulin (2 x 10(-5)-2 x 10(-4) M) produced negative inotropic effects. On the other hand in the membrane action potential of papillary muscles, tiamulin (2 x 10(-6)-2 x 10(-4) M) produced decreases in action potential and durations and 2 x 10(-4) M tiamulin depressed the slow response action potential in depolarized muscles. Tiamulin produced prolongations of the PR interval in ECG, negative chrono- and inotropic effects, and an increase in perfusion flow in guinea-pig isolated and perfused hearts. These effects of tiamulin on the aorta or cardiac muscle were similar to those of verapamil and nifedipine. These results suggest that both the inhibitory action of tiamulin on the high K(+)-induced contraction in the aorta and the negative inotropic effect of tiamulin on the cardiac muscle are due to an inhibition of Ca2+ entry through the voltage-dependent Ca2+ channels of cells of both these muscles.

Action Potentials↗
PubMed1992

Postmortem changes of triazolam concentrations in body tissues.

Postmortem changes of triazolam concentrations in body tissues were examined using rats, in order to find the most suitable tissue samples for toxicological analysis. Triazolam was orally given to rats (5 mg/kg), and then the rats were sacrificed 1 hour after administration. Tissue samples were collected 0, 1 and 2 days after storage at 22-24 degrees C, and the triazolam concentration in each sample was measured using gas chromatography with a nitrogen phosphorus detector. Triazolam concentrations were markedly increased in the spleen, the abdominal muscle, the liver and the kidney, and were slightly increased in the blood and the lung. On the other hand, no changes were observed in the thigh muscle or the brain, and the value in the thigh muscle was similar to those in the blood samples collected immediately after death. The results indicate that triazolam diffuses into the surrounding tissues through the stomach wall after death, so that the thigh muscle and the brain have to be analyzed as well as the blood for a correct diagnosis of triazolam ingestion.

Administration, Oral↗
PubMed1992

[Effects of ulinastatin on endotoxin shock in dogs].

The therapeutic effect of ulinastatin, an inhibitor of the protease activity, on endotoxin shock was evaluated using 17 Beagle dogs. Single intravenous injection of ulinastatin at a dose of 5,000 or 25,000 U.kg-1 failed to suppress the endotoxin-induced circulatory disturbance but significantly inhibited increases in pulmonary arterial pressure and pulmonary vascular resistance that occur early following administration of endotoxin. Elevation of PGI2, TXA2 and LTB4 by endotoxin shock was significantly inhibited by administration of 25,000 U.kg-1 of ulinastatin. Elevation of the granulocytic elastase activity was inhibited dose-dependently by administration of ulinastatin. The above results indicate that ulinastatin may be a promising drug for the treatment of endotoxin shock.

Animals↗
PubMed1991

Effects of pirarubicin, an antitumor antibiotic, on the cardiovascular system.

In the present study we examined the effects of pirarubicin [(2"R)-4'-O-tetrahydropyranyladriamycin, THP] on a cardiovascular system. An injection of THP (0.39-3.13 mg/kg, i.v.) reduced the mean blood pressure and caused an increase in the respiratory air rate in anesthetized rats. At 1.5 x 10(-6)-1.5 x 10(-5) M, THP markedly relaxed a contraction induced by 10(-7) M norepinephrine in rat aorta with endothelium but not in that without endothelium. At a dose of 0.02-0.5 mg, THP produced an increase in the contractile force and the perfusion flow of isolated perfused guinea pig hearts. At a higher concentration (4.5 x 10(-5)-1.5 x 10(-4) M), it produced a slight increase in the contractile force of the left atria in guinea pigs. This positive inotropic action of THP was inhibited by diphenhydramine (10(-6)-5 x 10(-5) M), chlorpheniramine (3 x 10(-7)-3 x 10(-5) M), and tripelennamine (3 x 10(-7)-3 x 10(-5) M) but not by propranolol (10(-6) M), cimetidine (10(-5) M), diltiazem (10(-6) M), or ryanodine (10(-8) M). THP given i.v. at 2.5 mg/kg elevated the plasma histamine level in anesthetized dogs. From these data, we conclude that THP mainly relaxed the rat aorta in the presence of endothelium and that at higher concentrations, it increased the contractile force in the cardiac muscle, probably mediated through the release of histamine.

Animals↗
PubMed1991

Pirarubicin-induced endothelium-dependent relaxation in rat isolated aorta.

The mechanism of relaxation produced by pirarubicin [(2"R)-4'-O-tetrahydropyranyladriamycin, THP] has been studied in rat isolated aorta. THP (1.5 x 10(-6)-4.5 x 10(-5) M) markedly relaxed contractions induced by noradrenaline (10(-7) M) in the aorta with endothelium, but not in that without endothelium. The relaxation induced by 1.5 x 10(-5) M THP was inhibited by methylene blue (5 x 10(-6) M), hydroquinone (10(-4) M), phenidone (5 x 10(-5) M), haemoglobin (10(-6) M) and p-bromophenacyl bromide (5 x 10(-5) M), but not by indomethacin (2.5 x 10(-5) M). The relaxation induced by THP (1.5 x 10(-7) -4.5 x 10(-5) M) was inhibited by NG-nitro-L-arginine (10(-5) M), but enhanced by superoxide dismutase (10 units mL-1) or by L-arginine (10(-2) M). However, the THP-induced relaxation was not inhibited by various receptor antagonists such as atropine (10(-6) M), cimetidine (10(-5) M), diphenhydramine (3 x 10(-6) M) and [D-Pro4, D-Trp7,9,10]-substance P(4-11) (1.5 x 10(-6) M). In fifteen anthracycline analogues, THP and 13-dihydropirarubicin (both with a tetrahydropyranyl group) produced endothelium-dependent relaxations. These results suggest that the THP-induced relaxation which is probably mediated by endothelium-derived relaxing factor (EDRF) was not produced by an activation of muscarine, histamine H1 or H2, or substance P receptor, and further that the tetrahydropyranyl group must play an important role in the THP-induced relaxation.

Animals↗
PubMed1991

Decrease in muscle tension and reduced pyridine nucleotides of the guinea pig ileal longitudinal smooth muscle in high K+,Na(+)-deficient solution.

In the present experiment, we studied the inhibitory mechanism of Na+ depletion on high K(+)-induced contraction by simultaneously measuring reduced pyridine nucleotides (PNred) or oxidized flavoproteins (FPox) fluorescence and contractile tension of the guinea pig ileal longitudinal muscle. Tension, PNred and FPox were all reversibly increased by the addition of hyperosmotic 65 mM KCl (H-65K+). A high K+, Na(+)-deficient (Iso-154K+) solution induced a contraction followed by a gradual relaxation and gradually decreased PNred fluorescence. A hyperosmotic addition of NaCl to the Iso-154K+ solution prevented the decreases in tension and PNred fluorescence. Addition of pyruvate or oxaloacetate restored the decrease in Iso-154K(+)-induced contraction, but not the decrease in PNred fluorescence. In contrast to the PNred fluorescence, an application of the Iso-154K+ solution increased the FPox fluorescence which was not significantly changed by an addition of NaCl, pyruvate or oxaloacetate. These results suggest that the inhibitory mechanism of Na+ depletion on the Iso-154K(+)-induced contraction is an inhibition of glucose utilization.

Animals↗
PubMed1991

The inhibitory effect of tiamulin on high K(+)-induced contraction in guinea pig intestinal smooth muscle.

Tiamulin with an IC50 of 1.7 x 10(-6) M inhibited both the rapid and sustained contractions induced by hyperosmotically added 60 mM K+ (Hyper 60 K+) without changing the membrane potential in the intestinal muscle. Tiamulin inhibition (2 x 10(-6)-2 x 10(-5) M) of the Ca(2+)-induced contraction in depolarized muscle was competitively antagonized by raising external Ca2+. Tiamulin (2 x 10(-5) M) slightly affected the Hyper 60 K(+)-induced phasic contraction under hypoxia and the carbachol-induced phasic contraction. Moreover, tiamulin (2 x 10(-5) M) inhibited the Hyper 60 K(+)-induced contraction with decreasing [Ca2+]cyt level. Although the inhibitory effect of 10(-7)-10(-5) M monesin, an inhibitor of mitochondrial respiration, on the Hyper 60 K(+)-induced contraction was reduced under hypoxia, the effect of tiamulin (2 x 10(-7)-2 x 10(-4) M) was not modified. Tiamulin changed neither the intracellular Na+ and K+ content of the depolarized muscle nor the Ca(2+)-induced contraction in the chemically skinned preparations. These results suggest that the inhibitory action of tiamulin on the Hyper 60 K(+)-induced tonic contraction is possibly due to the competitive inhibition of Ca2+ entry through the voltage-dependent Ca2+ channel of the intestinal smooth muscle cell.

Animals↗
PubMed1990

Disorders of bone metabolism caused by small bowel resection in rats.

Disorders of bone metabolism caused by resection of three quarters of the small bowel in rats were investigated biochemically and histomorphologically. Metabolic bone disorders developing 90 days after in 75%-distal-small-bowel resected rats were characterized by reduction in ash content of the femur and by the disappearance of the trabecular bone in tibial metaphysis. Biochemical studies showed significant decrease in serum Ca and 1,25-dihydroxyvitamin D concentrations in 75% distal small bowel resected rats. These data suggest that 75% distal small bowel resection impairs intestinal absorption of calcium and results in a negative calcium balance, which may contribute to the development of bone metabolic disorder in rats. On the other hand, 75% proximal small bowel resection causes no obvious metabolic bone disorders in rats, possibly because of the adaptation by the remaining part of the intestine.

Animals↗
PubMed1990

A change in inhibitory mechanism of Na+ deficiency on high K(+)-induced contraction in rat uterus with the progress of pregnancy.

In the present paper, effects of high K+/Na+ deficient solution on the rat uterus with the progress of the pregnancy were examined on the mechanical response and wet weight. The progress of pregnancy was divided in four stages, early stage (Day 4 and 5 of pregnancy), middle stage (Day 8-10), late stage (Day 14 and 15) and end stage (Day 21). In the early stage muscle, an isosmotically substituted high K+/Na+ deficient (iso-154K+) solution induced a large contraction followed by a decrease in tension level, though a hyperosmotic KCI addition induced a large sustained contraction. Similar results were shown in muscles of the middle and late stages. However, a maximum tension level and a subsequent inhibition by the iso-154K+ solution in the end stage muscle were smaller than those of other stages. On the other hand, iso-154K+ solution remarkably increased the relative cellular water content in the early or middle stage muscle, but moderately in the late or end stage one. In the muscle of all stages, a hyperosmotic addition of sucrose reversed the inhibition of muscle tension and the cell swelling by the iso-154K+ solution. Moreover, a substitution of more impermeable anion (C2H5COO-) for Cl- in the iso-154K+ solution decreased the inhibition of the contraction in the early stage muscle, but increased it in the end stage one. The substitution for Cl- with more permeable anion (NO3- or I-) produced a greater inhibition of contraction in all stage muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Inhibitory effect of lithium on muscle contractions caused by various stimulants in guinea-pig ileum.

The tonic contractions induced in the guinea-pig ileal longitudinal muscle by 60 mM KCl, carbachol, histamine or A23187 were inhibited similarly by Li+-substituted solution. There was a good correlation between the Li+-induced inhibition of contractions induced by these stimulants and the intracellularly accumulated Li+ content. In the experiment with fura-2, Li+-substituted solution inhibited the high-K+-induced contraction without decreasing the cytosolic Ca2+ level elevated by high-K+ solution. The concentration-response curve for Ca2+ in the skinned fiber was shifted to the right by pretreatment with Li+-substituted solution. These results suggest that the inhibitory mechanism of Li+ on the contractions by various stimulants partly involves the direct inhibition of the contractile proteins in the guinea-pig ileal longitudinal muscle.

Animals↗
PubMed1989

The effect of trifluoperazine on muscle tension and cytoplasmic Ca2+ level in guinea pig ileum.

In guinea pig ileal muscle strips, trifluoperazine (TFP) inhibited the high K+-induced contraction with an IC50 of 1.9 microM and the Ca2+-induced contraction in skinned fiber with an IC50 of 44 microM. TFP decreased the high K+-induced increase in cytoplasmic Ca2+ level at the concentration 3 microM, which did not inhibit the contraction in skinned fiber. It is suggested that the inhibitory effect of TFP on the high K+-induced contraction is mainly due to the decrease in cytoplasmic Ca2+.

Animals↗
PubMed1988

Inhibitory effects of caffeine on contractions and calcium movement in vascular and intestinal smooth muscle.

1. The mechanism of the inhibitory effect of caffeine was investigated using vascular smooth muscle of rabbit aorta and intestinal smooth muscle of taenia isolated from guinea-pig caecum. 2. Caffeine, 0.5-10 mM, relaxed the sustained contraction induced by 65.4 mM KCl or 10(-6) M noradrenaline in aorta, and by 45.4 mM KCl or 10(-6) M carbachol in taenia. The inhibitory effect of caffeine on the high K+-induced contraction was antagonized by external Ca2+ but not by the Ca2 channel activators, Bay K 8644 (10(-7) M) or CGP 28,392 (10(-7) M). Forskolin (2 x 10(-7) M) potentiated the inhibitory effect of caffeine on the noradrenaline-induced contraction but not on the high K+- or carbachol-induced contraction. Caffeine induced a time- and concentration-dependent increase in the cyclic AMP content of aorta and forskolin caused a further augmentation. 3. 45Ca2+ uptake was increased by high K+ or noradrenaline in aorta and by high K+ or carbachol in taenia. The increments were inhibited by caffeine at concentrations needed to inhibit muscle contractions. 4. 45Ca2+ in the cellular releasable site in aorta was decreased either by noradrenaline or by caffeine. Simultaneous application of noradrenaline and caffeine did not induce an additive decrease. 5. In aorta treated with a Ca2+-free solution, caffeine induced only a small contraction. Noradrenaline induced a greater contraction which was inhibited by caffeine. After washout of caffeine and noradrenaline, the second application of noradrenaline induced a transient contraction suggesting that caffeine does not deplete the noradrenaline-sensitive store. 6. It was concluded that caffeine has multiple sites of action in smooth muscle. Caffeine releases Ca2+ from a store which is apparently not sensitive to noradrenaline. Caffeine may inhibit noradrenalineinduced Ca2' release. Caffeine itself induces only a small contraction possibly because it decreases the Ca2+ sensitivity of contractile filaments and/or increases Ca2+ extrusion. Further, caffeine seems to inhibit stimulated Ca2+ influx. Cyclic AMP may be only partly responsible for the inhibitory effect of caffeine.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Palytoxin-induced K+ efflux from ileal longitudinal smooth muscle of the guinea-pig.

In guinea-pig ileal longitudinal smooth muscle, both palytoxin (PTX) and carbachol (CCh) increased K+ efflux with an EC50 of 1.8 X 10(-10) M and 4.1 X 10(-7) M, respectively. Atropine (10(-6) M) did not inhibit the K+ efflux due to PTX (3 X 10(-9) M), but completely inhibited the efflux due to CCh (10(-5) M). External Ca2+ removal and verapamil (10(-5) M) did not change the PTX-induced K+ efflux, although the CCh-induced K+ efflux was inhibited about 77% and 71%, respectively. PTX-induced K+ efflux was reduced to 31% by a depletion of intracellular Ca2+. Tetraethylammonium (15 mM) inhibited the K+ efflux due to PTX or CCh to 61% or 75%, respectively. The PTX-induced K+ efflux was also inhibited by cymarin (3 X 10(-8) M), ouabain (10(-5) M) and digitoxin (10(-5) M). These results suggest that the PTX-induced K+ efflux is less dependent on Ca2+ influx than that due to CCh. Furthermore, the binding sites for PTX in the ileal muscle of guinea-pig may be Na+, K+-ATPase, as has been suggested in other types of cells.

Acrylamides↗