Biomedical subjects

N Kawai

Publications and source records attributed to N Kawai.

At least 37 records · Page 2Linked to original sources

PubMed2002

A study of hypoxic cell radiosensitizer applied to Ehrlich ascite tumour: a comparison of FC43 emulsion and pentoxyfilline.

In this study, we examined the effects of various combinations of treatments involving radiation, injections of perfluorochemicals (FC-43 emulsion) and injections of pentoxifylline on the growth delay of Ehrlich ascite tumours. Ehrlich ascite tumour cells were transplanted into the legs of ddY-strain mice. Tumour-bearing mice were divided into seven groups: group 1, no treatment; group 2, irradiated only; group 3, injected with FC-43 emulsion and kept in a carbogen atmosphere; group 4, injected with pentoxifylline and nicotinamide; group 5, injected with FC-43 emulsion, kept in a carbogen atmosphere and irradiated; group 6, injected with pentoxifylline and nicotinamide and irradiated; and group 7, injected with FC-43 emulsion, pentoxifylline and nicotinamide, kept in a carbogen atmosphere and irradiated. When 20 Gy irradiation was applied, tumour growth delay was 11 days in group 2, 20 days in group 5, 22 days in group 6, and 24 days in group 7. For a growth delay of 20 days, the dose modifying factor was 1.95+/-0.04 (standard deviations) in group 5, 1.97+/-0.09 standard deviations in group 6, and 2.01+/-0.07 standard deviations in group 7. It was concluded that FC-43 emulsion and pentoxifylline did not have an interactive effect.

Animals↗

PubMed2001

Anoplin, a novel antimicrobial peptide from the venom of the solitary wasp Anoplius samariensis.

A novel antimicrobial peptide, anoplin, was purified from the venom of the solitary wasp Anoplius samariensis. The sequence was mostly analyzed by mass spectrometry, which was corroborated by solid-phase synthesis. Anoplin, composed of 10 amino acid residues, Gly-Leu-Leu-Lys-Arg-Ile-Lys-Thr-Leu-Leu-NH2, has a high homology to crabrolin and mastoparan-X, the mast cell degranulating peptides from social wasp venoms, and, therefore, can be predicted to adopt an amphipathic alpha-helix secondary structure. In fact, the circular dichroism (CD) spectra of anoplin in the presence of trifluoroethanol or sodium dodecyl sulfate showed a high content, up to 55%, of the alpha-helical conformation. A modeling study of anoplin based on its homology to mastoparan-X supported the CD results. Biological evaluation using the synthetic peptide revealed that this peptide exhibited potent activity in stimulating degranulation from rat peritoneal mast cells and broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria. Therefore, this is the first antimicrobial component to be found in the solitary wasp venom and it may play a key role in preventing potential infection by microorganisms during prey consumption by their larvae. Moreover, this peptide is the smallest among the linear alpha-helical antimicrobial peptides hitherto found in nature, which is advantageous for chemical manipulation and medical application.

Amino Acid Sequence↗

PubMed2001

Catecholamines and opioid peptides increase in plasma in humans during possession trances.

Naturally induced possession trances have been observed in healthy people of many societies. The neurophysiological basis of this phenomenon remains unknown, however, because of the difficulty in accessing subjects in trances due to their sacred context. In the present study, we measured the plasma levels of several neuroactive substances from subjects exhibiting or lacking possession trance characteristics during Balinese dedicatory dramas under natural conditions. The trance group exhibited significant increases in plasma concentrations of noradrenaline, dopamine and beta-endorphin, compared with controls who performed the same actions as the trance group. The present finding suggests that catecholamines and opioid peptides are involved in possession trances.

Adult↗

PubMed2001

Human prostate cancer cells adhere specifically to hemoglobin: a possible role in bone-specific metastasis.

From the supernatant of rabbit bone marrow, we isolated an organ-specific factor, which was related with the metastasis of prostate cancer to the bone and examined its adhesion to prostate cancer cells (PC-3). Molecular weight and amino acid sequence analyses of the active component obtained by high performance liquid chromatography revealed that a component identical to the alpha chain of hemoglobin accounted for 80% of the biological activity. Hemoglobin showed over 50% adhesion to PC-3 cells but only 10% adhesion to human colon cancer cell lines, representative of organ non-specific metastasis, and leukemia cells line, representative of a non-solid tumor. Some substance in the bone marrow may promote the first step of adhesion of cancer cells to bone marrow in the metastasis of prostate cancer to the bone, possibly an amino acid sequence or some tertiary structure similar to hemoglobin.

Animals↗

PubMed2001

Effects of hypothermia on thrombin-induced brain edema formation.

Recent studies have shown that thrombin plays an important role in brain edema formation after intracerebral hemorrhage (ICH). The possible mechanisms of thrombin-induced brain edema formation include blood-brain barrier (BBB) disruption and inflammatory response involving polymorphonuclear (PMN) leukocyte. Animal experiments have revealed that moderate therapeutic hypothermia improves pathological and functional outcome in various models of brain injury. In this study, we examined the effect of hypothermia on thrombin-induced brain edema formation. Effects of hypothermia on BBB permeability and the accumulation of PMN leukocytes were also determined to clarify the protective mechanism of hypothermia in this model. Anesthetized adult rats received an injection of 10 Units of thrombin into the basal ganglia. Animals were separated into the normothermic and hypothermic groups, which were housed in a room maintained at 25 degrees C and in a cold room maintained at 5 degrees C, respectively, for 24 h after the thrombin injection. The brain temperature in rats housed in a cold room reduced temporarily to approximately 30 degrees C and then gradually recovered to 35 degrees C by the end of the observation. Brain water content in the basal ganglia was significantly reduced in rats treated with hypothermia compared to the normothermic rats (84.3+/-0.2 vs. 82.4+/-0.1%; P<0.01). The decrease of brain water content was accompanied with a significant reduction in BBB permeability to Evan's blue dye and in accumulation of PMN leukocytes. This study indicates that hypothermic treatment significantly reduces thrombin-induced brain edema formation in the rat. Inhibition of thrombin-induced BBB breakdown and inflammatory response by hypothermia appear to contribute to brain protection in this model. Hypothermic treatment may provide an approach to potentially reduce ongoing edema after ICH.

Animals↗

PubMed2001

Confined band gap in an air-bridge type of two-dimensional AlGaAs photonic crystal.

The transmittance spectrum for an air-bridge type of AlGaAs photonic crystal (PC) slabs successfully fabricated was measured. It is found that the observed spectrum is consistent with both the theoretical band structure and the calculated one. Moreover, the transmittance due to the modes below the light line is found to be almost 100%, indicating that the guided modes should exist. The respective stop bands are observed in the gamma-M direction for TM-like and TE-like modes, implying that a photonic band gap should exist for the TE-like guided modes. The present PC is very suited for controlling the radiation field.

Journal Article↗

PubMed2001

Roles of arginine vasopressin and atrial natriuretic peptide in polydipsia-hyponatremia of schizophrenic patients.

Respective contributions of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) to the urinary sodium concentration were evaluated in 23 naturalistic incidents of polydipsia-hyponatremia observed in 11 hospitalized schizophrenics (10 males and 1 female). The sodium concentration of the spontaneously excreted urine was examined before and after the forced water restriction. Before the water restriction, mean (+/-S.D.) plasma ANP was 52.8 +/- 33.9 pg/ml (range = 6.9-137). Plasma AVP levels were below 0.3 pg/ml in 15 episodes; relatively high levels (> or = 0.3) were noted in eight episodes. Means of urinary sodium concentration (mEq/l) were significantly higher in episodes with high AVP (> or = 0.3) alone (25.0 +/- 8.2, n=4), with high ANP (> 43) alone (21.3+/-7.4, n = 9), and with high AVP and ANP (26.8 +/- 6.4, n = 4) as compared to that of the low AVP (< 0.3) and ANP (< or = 43) group (13.5 +/- 3.7, n = 6). The data indicate that the elevated urinary sodium in polydipsic patients is possibly due to the AVP-induced antidiuresis and/or the ANP-induced natriuresis. In addition, we observed a close relationship between elevated plasma AVP and vomiting, suggesting that vomiting is one of the causal factors responsible for AVP elevations in this syndrome.

Adult↗

PubMed2001

Modulation of synaptic transmission in hippocampal CA1 neurons by a novel neurotoxin (beta-pompilidotoxin) derived from wasp venom.

We examined the effects of beta-pompilidotoxin (beta-PMTX), a neurotoxin derived from wasp venom, on synaptic transmission in the mammalian central nervous system (CNS). Using hippocampal slice preparations of rodents, we made both extracellular and intracellular recordings from the CA1 pyramidal neurons in response to stimulation of the Schaffer collateral/commissural fibers. Application of 5-10 microM beta-PMTX enhanced excitatory postsynaptic potentials (EPSPs) but suppressed the fast component of the inhibitory postsynaptic potentials (IPSPs). In the presence of 10 microM bicuculline, beta-PMTX potentiated EPSPs that were composed of both non-NMDA and NMDA receptor-mediated potentials. Potentiation of EPSPs was originated by repetitive firings of the presynaptic axons, causing summation of EPSPs. In the presence of 10 microM CNQX and 50 microM APV, beta-PMTX suppressed GABA(A) receptor-mediated fast IPSPs but retained GABA(B) receptor-mediated slow IPSPs. Our results suggest that beta-PMTX facilitates excitatory synaptic transmission by a presynaptic mechanism and that it causes overexcitation followed by block of the activity of some population of interneurons which regulate the activity of GABA(A) receptors.

2-Amino-5-phosphonovalerate↗

PubMed2001

Repeated thalamic haemorrhage: case report and review of the literature.

Recurrence of thalamic haemorrhage has rarely been reported. A 70-year-old woman had recurrent thalamic haemorrhage five-times during a period of 6 years. The first, second and fifth haemorrhages were located in the right thalamic region, and the third and fourth haemorrhages in the left thalamic region. Cranial computed tomography and magnetic resonance imaging revealed no abnormal lesion. After the first, second, and third haemorrhage with medical treatments, the patient recovered her functional ability or was at least capable of self-care at home. However, after the fourth and fifth haemorrhage, with medical therapy the patient's prognosis was severe disability. In this case, systemic blood pressure was normalized without antihypertensive agents after the first attack. However, there was an episode of sudden hypertension at each attack. Although the mechanism of rebleeding has not been clarified, rebleeding might be associated with changes of cerebral circulation following the previous haemorrhage.

Aged↗

PubMed2001

KAI1 expression can be a predictor of stage A prostate cancer progression.

The disease progression and rate of cancer death were analyzed in 52 patients with stage A prostate cancer who underwent transurethral resection of the prostate (TURP) or retropubic subcapsular prostatectomy (SCP) between 1987 and 1998. We performed immunohistochemistry on 16 patients to determine the correlation between the expression of the tumor metastasis suppressor gene KAI1 and the subsequent progression of stage A prostate cancer. Nineteen and 33 of the patients had cancer at stage A1 and stage A2, respectively, and their subsequent courses were followed for an average of 53.7 months (24-134 months). Progression to clinical cancer was found in six patients (one with stage A1, and five with stage A2). This progression was evident 40.8 months (5-80 months) after TURP or SCP. Four (66.7%) of the patients died of cancer progression (average 31 months) after prostatectomy. All four patients had stage A2, poorly differentiated adenocarcinoma, and had been followed with administration of diethylstilbestrol diphosphate (DES-P). The disease-free patients (n=10) showed overexpression of KAI1 protein, compared to those with disease progression (n=6). These results indicate that progression arose mainly in the patients with stage A2 cancer, and that poorly differentiated, focal and weak expression of KAI1 protein is highly associated with disease progression. It is suggested that patients in this group should be treated with immediate total androgen blockade, radiation, or radical prostatectomy after diagnosis.Prostate Cancer and Prostatic Diseases (2001) 4, 150-153.

Journal Article↗

PubMed2001

Comparison of three-dimensional computed tomography with rapid prototype models in the management of coronoid hyperplasia.

OBJECTIVES: To compare (1) the accuracy of 3DCT with rapid prototyping (RP) models and (2) their application in the management of coronoid hyperplasia. METHODS: An adult dry skull was used to compare 3DCT and a RP model for accuracy of reproduction; Polymerisation contraction and 17 distances between 27 anatomical points were measured. Two patients with coronoid process hyperplasia were assessed by means of 3DCT and plastic models. RESULTS: Differences in measurements with the RP model and the dried skull were smaller than those with 3DCT (P=0.04). Polymerisation contraction was greater than the errors in reproduction with the RP model and approximately equal to those with the 3DCT. The coronoid process was thick and prominent in the patients with coronoid process hyperplasia and the small space and early contact between zygomatic arch and the coronoid process demonstrated. The plastic model duplicated the exostosis of the inner surface of the malar bone facing the concavity of the elongated process. The coronoid process had an anterior tilt in one case. CONCLUSION: The plastic model duplicated the relationship between the maxillofacial deformity and the coronoid process with tolerable accuracy. Trismus may be due to the direction as well as the length of the enlarged coronoid process.

Adolescent↗

PubMed2001

Effects of osutidine (T-593) and its enantiomers on gastric mucosal hemodynamics and mucosal integrity in anesthetized rats.

T-593 (osutidine, CAS 140695-21-2) is a new anti-ulcer agent that consists of two enantiomers, (+)-(R)-T-593 and (-)-(S)-T-593. The present study was designed to investigate the effects of T-593, (+)-(R)-T-593 and (-)-(S)-T-593 on ethanol-induced gastric damage in rats. Rats were given intraperitoneal administration of vehicle, racemic T-593, (+)-(R)-T-593 or (-)-(S)-T-593. 30 min later, the rats intragastrically received a 1-ml solution of 40% ethanol, and 30 min thereafter, they were sacrificed for assessment of gastric damage. Gastric hemodynamics were assessed by reflectance spectrophotometry and laser Doppler flowmetry during the experiment. Gastric damage was significantly suppressed by racemic T-593 in a dose-dependent manner. While 60 mg/kg of (+)-(R)-T-593 and (-)-(S)-T-593 also suppressed ethanol-induced gastric injury, the same dose of racemic T-593 exerted the most potent anti-ulcerative activity. Both (+)-(R)-T-593 and racemic T-593 increased gastric mucosal blood flow and abolished gastric mucosal blood flow stasis induced by 40% ethanol. Although (-)-(S)-T-593, which antagonizes histamine H2-receptors, exerts an antiulcerative effect, (+)-(R)-T-593 also protects the gastric mucosa from ethanol-induced injury, possibly by influencing gastric mucosal hemodynamics. Thus racemic T-593 may protect the gastric mucosa by antagonizing H2-receptors and by enhancing gastric circulation in rats.

Anesthesia↗

PubMed2001

Protective effects of FK409, a novel nitric oxide donor, against postischemic myocardial dysfunction in guinea-pig hearts.

Effects of FK409 were investigated in perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion. Nitric oxide electrode, fluorometry, and 31P nuclear magnetic resonance imaging were used to monitor changes in cellular high-phosphorous energy and nitric oxide and Ca2+ content in the heart together with simultaneous recordings of left ventricular developed pressure. After cardioplegic arrest with St. Thomas' Hospital solution, normothermic (37 degrees C) global ischemia was induced for 40 min, and hearts were reperfused for 40 min. FK409 at 10(-8) M, which has a minimum inotropic effect on nonischemic hearts, was added to the cardioplegic solution. Treatment with FK409 reduced left ventricular developed pressure during and after ischemia and improved postischemic recovery of left ventricular developed pressure from 55.4% at 40 min of reperfusion in FK409-free hearts up to 80.4% in hearts treated with FK409 (p < 0.01). Flow rate at 1.5 min after treatment with the cardioplegic solution was 27.7 ml/min in hearts treated with FK409 compared with 21.2 ml/min in drug-free hearts (p < 0.01). Treatment with FK409 significantly effected preservation of tissue level of beta-adenosine triphosphate at the end of ischemia or reperfusion. During ischemia, arrested with the cardioplegic solution, intracellular Ca2+ accumulation and nitric oxide release were reduced. At the end of ischemia in FK409-treated hearts, nitric oxide release was 86% greater than in drug-free hearts without reference to the Ca2+ concentration. In cardiac surgery, normothermic arrested hearts are subject to damage by oxygen free radicals in reperfusion injury. Therefore, nitric oxide exogenously supplied by FK409 was responsible for the cardioprotective action, presumably by acting directly as an oxygen radical scavenger during reperfusion. A specific nitric oxide donor, like FK409, may have therapeutic use as a nitric oxide-mediated vasorelaxant and additional protective action for reperfusion-injury hearts.

Actin Cytoskeleton↗

PubMed2001

Long-term activation of the glutamatergic system associated with N-methyl-D-aspartate receptors after postischemic hypothermia in gerbils.

OBJECTIVE: The objective of this study was to investigate whether hypothermia would suppress secondary damage in the chronic postischemic stage, in terms of glutamate excitotoxicity. METHODS: Gerbils underwent 5 minutes of ischemia via bilateral common carotid artery occlusion. Seven groups were studied, as follows: 1) ischemia without treatment group; 2) intraischemic hypothermia group; 3) postischemic hypothermia group (32 degrees C for 4 h); 4) MK-801 treatment group (2 mg/kg, every other day for 1 mo); 5) postischemic hypothermia with MK-801 treatment for 1 week group (2 mg/kg, every other day); 6) postischemic hypothermia with MK-801 treatment for 1 month group (2 mg/kg, every other day); and 7) sham-treated control group. One month after ischemia, histological changes in hippocampal CA1 neurons (assessed using hematoxylin and eosin staining) and memory function (assessed using an eight-arm radial maze) were studied. Extracellular glutamate concentrations were monitored by microdialysis during ischemia and hypothermia. Staining of microglia was performed 1 week and 1 month after ischemia. RESULTS: MK-801 alone, postischemic hypothermia alone, and postischemic hypothermia with MK-801 treatment for 1 week failed to prevent ischemic neuronal damage and memory function decreases 1 month after the insult (P < 0.05 versus control). However, the postischemic hypothermia with MK-801 treatment for 1 month group exhibited significant protective effects (not significant [P > 0.05] compared with the control group). Extracellular glutamate levels for the intraischemic hypothermia group were significantly low, compared with the postischemic hypothermia group. There was no microglial activation in the postischemic hypothermia at 1 week and 1 month after ischemia groups. CONCLUSION: Postischemic hypothermia and long-term intermittent administration of MK-801 demonstrated significant neuronal protection, indicating that long-term glutamatergic activation, with changes in N-methyl-D-aspartate receptors, plays a role in neuronal damage in the chronic postischemic stage.

Animals↗

PubMed2001

[Clinical analysis of neutropenic fever associated with hematological disorders].

We evaluated the efficacy of combination therapy with sulbactam/cefoperazone (SBT/CPZ) and amikacin sulfate (AMK) in eligible patients with hematological disorders of neutrophil count less than 1,000/microliter. The clinical efficacy rate in 157 evaluated patients was 65.6%. The clinical efficacy rates were related to neutrophil counts and serum albumin levels at the 1 week later. The clinical efficacy rates were 87.1% in patients with neutrophil counts over 500/microliter and 34.8% in patients with serum albumin levels under 3 g/dl after 1 week. G-CSF treatment were not significant but tended to be more effective in patients with sepsis, and the neutrophil counts increased significantly. The group using G-CSF before the antibiotic treatment had a high clinical efficacy rate. It is suggested that G-CSF is effective in patients with neutropenia with the high risk to infection and in those who already have severe infections.

Adolescent↗

PubMed2001

Hepatocellular carcinoma: involvement of the internal mammary artery.

PURPOSE: To investigate factors related to the development of internal mammary arteries (IMAs) as feeding arteries of hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: In 30 patients with HCC located in ventral hepatic areas directly beneath the diaphragm, bilateral internal mammary arteriography was performed to explore involvement of the IMA with HCC. The number of previous transcatheter arterial embolizations (TAEs), tumor size, time from initial TAE to IMA angiography, inferior phrenic artery (IPA) involvement with tumor, presence of hepatic artery occlusion, and use of other treatments were compared in groups with and without involvement of the IMA. RESULTS: The group with IMA involvement included 10 patients; the group without involvement, 20 patients. TAE had been performed two to 12 times in the group with involvement and zero to six times in the group without involvement (P =.01). Mean tumor sizes in these two groups were 5.1 and 6.0 cm, respectively; hepatic artery occlusion was noted in nine and zero patients (P =.01) in the two groups. The time from initial TAE to IMA angiography ranged from 3 to 53 months (median, 31.5 months) and from zero to 89 months (median, 0 months) (P =.01). IPA involvement was observed in seven and four patients (P =.015). CONCLUSION: These results strongly suggest that, regardless of tumor size, when HCCs are located in the ventral hepatic areas directly beneath the diaphragm, the IMAs serve as feeding arteries in patients with hepatic artery occlusion caused by repeated TAE.

Aged↗

PubMed2001

Intravesical combined chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin is not indicated for superficial bladder cancer.

PURPOSE: The short-term effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) administered repeatedly for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 24 patients aged a median of 70 years between March 1996 and February 1999, and were compared with those of BCG monotherapy in 50 patients from March 1990 to February 1999. PATIENTS AND METHODS: The patients underwent intravesical instillation of the Tokyo strain BCG with or without epirubicin after transurethral resection (TUR) of bladder cancer. For the combined treatment, at 1-2 weeks after TUR, epirubicin (40 mg) and BCG (80 mg) were istilled into the bladder by turns once a week for 12 weeks. For the group receiving only BCG, 80-mg instillations were done with the same schedule. Thereafter, the patients were followed by cystoscopy and urinary cytology every 3 months for up to 3 years after intravesical therapy. RESULTS AND CONCLUSIONS: At 2 years after treatment, the simple recurrence rate was 26.1% (6/23) in patients with chemoimmunotherapy and 32.0% (16/50) in BCG-treated patients. Adverse reactions, including increased frequency of urination, urgency and miction pain, were observed in 18 patients (85.7%) undergoing chemoimmunotherapy and 58.0% undergoing BCG monotherapy. One patient receiving chemoimmunotherapy was withdrawn from treatment because of symptoms of severe bladder irritation due to the instillation. Intravesical chemoimmunotherapy using epirubicin and BCG was finally found to be inferior in comparison with BCG monotherapy for the prophylaxis of recurrence of superficial bladder cancer.

Adjuvants, Immunologic↗

PubMed2001

Acute effects of E-3174, a human active metabolite of losartan, on the cardiovascular system in tachycardia-induced canine heart failure.

The aim of this study was to evaluate the acute effects of E-3174, a human active metabolite of the AT1 receptor antagonist, losartan, on hemodynamic functions in dogs with severe heart failure (HF). In dogs, insignificant plasma levels of E-3174 are present following administration of losartan, and therefore, the effects of these two drugs can be studied independently in the dog. HF was established by rapid pacing of the right ventricle (250-270 beats/min) for 4 weeks. We examined changes in cardiovascular functions after acute intravenous administration of losartan (1 mg/kg) and E-3174 (0.3 and 1 mg/kg), as well as an ACE inhibitor, enalapril (0.3 and 1 mg/kg), under condition of HF. The HF before treatment was characterized by increases in pre- and after-load of the left ventricle (LV), consequent low cardiac output, and LV dilatation. E-3174 at 0.3 and 1 mg/kg reduced pulmonary artery pressure (-13+/-6% and -22+/-3% from baseline, respectively, p<0.05), pulmonary capillary wedge pressure (-18+/-4% and -36+/-10%, p<0.05) and mean arterial pressure (-24+/-2% and -36+/-7%, p<0.05), increased stroke volume (SV: +12+/-7% p>0.05; +36 +/-19%, p<0.05), and reduced peripheral resistance (-23+/-5% and -41+/-9%, p<0.05), but had no effect on the first derivative of left ventricular pressure (dP/dt/P) or the time constant for relaxation. Effects of losartan at 1 mg/kg were similar to those of 0.3 mg/kg of E-3174. Enalapril at 1 mg/kg caused changes comparable to those seen after E-3174 administration (1 mg/kg), except that the increase in SV (+16+/-8%, p<0.05) with enalapril was not as great as that with E-3174. Both losartan at 1 mg/kg and E-3174 at 0.3 and 1 mg/kg increased fractional shortening to a similar extent (FS: +52+/-12%, +47+/-8% and +56+/-8%), while enalapril at 0.3 and 1 mg/kg had no significant effects on FS. Reflex elevation of plasma renin activity induced by 1 mg/kg of E-3174 was similar to that caused by 1 mg/kg of enalapril, suggesting that the two drugs achieved similar inhibition of the endogenous renin angiotensin system. Our study demonstrated that acute blockade of the AT1 receptor with E-3174 reduced elevated pre- and after-load and consequently increased stroke volume in a canine HF model. With the exception of changes in stroke volume, these effects of E-3174 were comparable to those produced by enalapril, and were 3 times stronger than those by losartan.

Angiotensin Receptor Antagonists↗