Biomedical subjects

T Sakamoto

Publications and source records attributed to T Sakamoto.

At least 127 records · Page 7Linked to original sources

PubMed2001

Improved fish lymphocyte culture for chromosome preparation.

Cytogenetic methodology is still underdeveloped in fishes compared with mammals. Culture condition for fish lymphocytes was optimized to improve chromosome preparation using the rainbow trout (Oncorhynchus mykiss) as a model after changing the combination of parameters such as mitogens, incubation periods, media, cell components, and freshness of blood. The optimized culture condition included isolation of lymphocytes from fresh blood by a stirring method, their culture in medium 199 supplemented with 10% FBS, 18 microg/ml of phytohemagglutinin (PHA-W) and 100 microg/ml of lipopolysaccharide (LPS) as mitogens, and harvested at 6 days after culture. This condition provided a notably increased mitotic index (MI) of 4.3-10.0% in rainbow trout lymphocytes. In addition, the condition was highly reproducible as shown by the similar level of MI in cultured lymphocytes from 181 individuals without failure. Applicability of this method in a wide range of fish groups was also proven with Ml of 1.1-13.3% in cultured lymphocytes from other 16 freshwater species of Acipenseridae, Anguillidae, Solmonidae, Cyprinidae, and Centrarchidae, and five marine species of Sparidae, Kyphosidae, Paralichthyidae, and Scorpaenidae. Chromosome preparations of improved quality by the present method were successfully applied for the replication R-banding with incorporation of 5-bromo-2'-deoxyuridine and direct R-banding fluorescence in situ hybridization.

Animals↗

PubMed2001

Effect of melatonin on sleep and rectal temperature of young healthy evening types.

The present study assessed in healthy nocturnal juveniles the presence or absence of the hypnotic action of exogenous melatonin and its effect on core temperature by oral administration of exogenous melatonin at a pharmacologically low dose 15 min before going to bed at the normal time. Both sleep latency and the number of instances of waking up after falling asleep tended to decrease, while the amount of Stage 2 sleep increased significantly. However, no hypothermic action regarding the rectal temperature for changes in the circadian phase were observed. According to those results, it is possible that exogenous melatonin has some direct hypnotic action on habitual night sleep, although the extent of this action is considered to be relatively weak.

Administration, Oral↗

PubMed2001

Hypnotic action of melatonin during daytime administration and its comparison with triazolam.

The present study was conducted to assess hypnotic action, effects on rectal temperature and dose dependency by daytime administration of exogenous melatonin (MLT) at 1 mg, 3 mg or 6 mg to subjects consisting of seven healthy juvenile adults. As a result, exogenous MLT significantly increased total sleep time and sleep efficiency, and MLT 6 mg was observed to demonstrate hypnotic effects that were nearly equal to those of triazolam at 0.125 mg. Rectal temperature was significantly decreased at MLT 1mg and 3 mg, there were no significant differences observed in the hypothermic effects at MLT 6 mg. These results indicate that exogenous MLT had dose-dependent hypnotic action on daytime sleep, and it is possible to consider that this hypnotic action was based on a direct-acting mechanism.

Adult↗

PubMed2001

Control strategy for rotary blood pumps.

The control strategy for ventricular support with a centrifugal blood pump was examined in this study. The control parameter was the pump rpm that determines pump flow. Optimum control of pump rpm that reflects the body's demand is important for long-term, effective, and safe circulatory support. Moreover, continuous, reliable monitoring of ventricular function will help successfully wean the patients from the ventricular assist device (VAD). The control strategy in this study includes determination of the target pump rpm that can provide the flow required by the body, fine-rpm-tuning to minimize deleterious effects such as suction in the ventricle, and assessment of ventricular function for successful weaning from VADs. To determine the target pump rpm, we proposed to use the relation between the native heart rate and cardiac output, and the relation between the pump rpm and centrifugal pump output. For fine-tuning of the pump rpm, the motor current waveform was used. We computed the power spectral density of the motor current waveform and calculated the ratio of the fundamental to the higher order components. When this ratio was larger than approximately 0.2, we assumed there would be a suction effect in the ventricle. As for assessment of ventricular function, we used the amplitude of the motor current waveform. The control system implemented using a DSP functioned properly in the mock circulatory loop as well as in acute animal experiments. The motor current also showed a good correlation with the ventricular pressure in acute animal experiments.

Animals↗

PubMed2001

Design and evaluation of a single-pivot supported centrifugal blood pump.

In order to develop a centrifugal blood pump that meets the requirements of a long-term, implantable circulatory support device, in this study a single-pivot bearing supported centrifugal blood pump was designed to evaluate its basic performance. The single-pivot structure consisted of a ceramic ball male pivot mounted on the bottom surface of the impeller and a polyethylene female pivot incorporated in the bottom pump casing. The follower magnet mounted inside the impeller was magnetically coupled to the driver magnet mounted on the shaft of the direct current brushless motor. As the motor rotated, the impeller rotated supported entirely by a single-pivot bearing system. The static pump performance obtained in the mock circulatory loop revealed an acceptable performance as a left ventricular assist device in terms of flow and head pressure. The pump flow of 5 L/min against the head pressure of 100 mm Hg was obtained at rotational speeds of 2,000 to 2,200 rpm. The maximum pump flow was 9 L/min with 2,200 rpm. The maximum electrical-to-hydraulic power conversion efficiency was around 14% at pump flows of 4 to 5 L/min. The stability of the impeller was demonstrated at the pump rpm higher than 1,400 with a single-pivot bearing without an additional support at its top. The single-pivot supported centrifugal pump can provide adequate flow and pressure as a ventricular assist device, but its mechanical stability and hemolytic as well as thrombotic performances must be tested prior to clinical use.

Equipment Design↗

PubMed2001

Estimation of left ventricular recovery level based on the motor current waveform analysis on circulatory support with centrifugal blood pump.

In a mock circulatory loop simulating the left heart bypass using a centrifugal blood pump, analysis of the motor current waveform of the centrifugal pump was performed to derive a useful parameter to evaluate the status of ventricular function. The relationship between the peak, amplitude, and the peak of the fundamental frequency of the power spectral density of the periodic motor current waveform (MCpsdP) that reflected the pulsatile ventricular pressure, and the peak of the left ventricular pressure (LVP) was examined. Although both peak and amplitude of the motor current waveform showed an excellent correlation with the peak LVP, they failed to predict the opening of the aortic valve. The MCpsdP that corresponds to the frequency of the heart rate showed an excellent correlation with the peak LVP throughout the LVP levels, but the slope between them changed with the opening of the aortic valve. Thus, it is possible to follow the change in the LVP and detect even the opening of the aortic valve, and, hence, the recovery of the left ventricle. However, the slope of the linear regression equation varied, depending on the pump speed. This result implies that the MCpsdP can be possibly used to follow the change of ventricular function during circulatory assistance with a centrifugal blood pump as well as to control the pump speed in response to varying ventricular function.

Centrifugation↗

PubMed2001

Establishment and characterization of immortalized Schwann cells from murine model of Niemann-Pick disease type C (spm/spm).

Niemann-Pick disease type C (NPC) is characterized by an accumulation of unesterified cholesterol in the endosomal/lysosomal (E/L) system, resulting in progressive neurodegeneration and death during early childhood. To investigate the cellular pathomechanism of nervous system involvement in NPC, continuous neural cell lines are desirable. In this study, we obtained neuronal and Schwann cell cultures and established spontaneously immortalized Schwann cell lines from dorsal root ganglia and peripheral nerves of NPC model mouse (spm/spm). One of the cell lines, designated SPMS9, had distinct Schwann cell phenotypes and was maintained over 10 months without phenotypic alterations. The level of Npc1 mRNA was markedly decreased, and NPC1 protein was not detectable in SPMS9 cells. These cells contained intracytoplasmic granules positive for filipin cholesterol staining and immunoreactive for GM2 ganglioside. Electron-microscopically, intracytoplasmic polymorphous membranous inclusions and vacuoles were demonstrated in SPMS9 cells. The treatment with an inhibitor of ceramide-specific glucosyltransferase, N-butyldeoxynojirimysin (NB-DNJ) markedly reduced the intracytoplasmic granular immunofluorescence for GM2 ganglioside in SPMS9 cells, whereas the amount of filipin-positive granules remained unchanged. The SPMS9 cells retained vesicular fluorescence of cationic dye acriflavine 16-24 hours after loading, indicating the defect of transmembrane efflux pump activity of NPC1 in the E/L compartment in these cells. These immortalized Schwann cells can be useful in studies on the nervous system lesions in NPC.

Animals↗

PubMed2001

Higher hematocrit improves liver blood flow and metabolism during cardiopulmonary bypass in piglets.

OBJECTIVES: Hemodilution has been applied conventionally during cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) to counteract the increase in viscosity and deleterious rheological effects caused by hypothermia. However, liver dysfunction after low-flow bypass and DHCA is common, and little is known about the effects of hematocrit (Hct). The purpose of the present study is to evaluate the impact of two hemodilution priming protocols used clinically on liver perfusion and metabolism. MATERIALS AND METHODS: Ten piglets were randomized into 2 groups. One group (n = 5) had a crystalloid prime resulting in an Hct of about 15 % (low hematocrit; group L), the other (n = 5) a total-blood prime (Hct = 25 %; high hematocrit; group H). All animals underwent 70 min cooling at full flow (150 ml/kg/min), 30 min of low flow (50 ml/kg/min) at 15 degrees C followed by 45 min of DHCA and 75 min of rewarming at full flow. Liver blood flow (LBF) was assessed at the beginning of CPB at 34 degrees C, at the end of cooling at 15 degrees C, at the end of low flow, 5 min after the start of warming, and at the end of rewarming at 34 degrees C by injections of radioactive microspheres. Liver function was evaluated at the same time using the MEGX test, which measures the metabolism of lidocaine. RESULTS: LBF was insignificantly reduced during cooling, decreased during low flow (p = 0.001), and increased again after DHCA with the highest flow at the end of rewarming. LBF tended to be lower at all times in group L (p = 0.096). The liver lidocaine metabolic rate did not significantly decrease during cooling and low flow, but was increased at the end of rewarming (p = 0.01); the metabolism was higher in group H (p = 0.025). Multiregression analysis revealed liver blood flow (p = 0.003) and hematocrit (p < 0.001) as independent determinants of the liver lidocaine metabolism; arterial blood pressure and temperature did not have significant influence in this model. CONCLUSION: Hemodilution results in a tendency towards reduced liver blood flow during CPB; much worse is the resulting impaired liver metabolism, independent of reduced blood flow and pressure. Avoidance of low hematocrit during CPB may be a useful adjunct to preserve liver function in patients undergoing cardiac surgery with long duration CPB and DHCA.

Animals↗

PubMed2001

Prediction of safe duration of hypothermic circulatory arrest by near-infrared spectroscopy.

OBJECTIVE: Hypothermic circulatory arrest is widely used for adults with aortic arch disease as well as for children with congenital heart disease. At present, no method exists for monitoring safe duration of circulatory arrest. Near-infrared spectroscopy is a new technique for noninvasive monitoring of cerebral oxygenation and energy state. In the current study, the relationship between near-infrared spectroscopy data and neurologic outcome was evaluated in a survival piglet model with hypothermic circulatory arrest. METHODS: Thirty-six piglets (9.36 +/- 0.16 kg) underwent circulatory arrest under varying conditions with continuous monitoring by near-infrared spectroscopy (temperature 15 degrees C or 25 degrees C, hematocrit value 20% or 30%, circulatory arrest time 60, 80, or 100 minutes). Each setting included 3 animals. Neurologic recovery was evaluated daily by neurologic deficit score and overall performance category. Brain was fixed in situ on postoperative day 4 and examined by histologic score. RESULTS: Oxygenated hemoglobin signal declined to a plateau (nadir) during circulatory arrest. Time to nadir was significantly shorter with lower hematocrit value (P <.001) and higher temperature (P <.01). Duration from reaching nadir until reperfusion ("oxygenated hemoglobin signal nadir time") was significantly related to histologic score (r (s) = 0.826), neurologic deficit score (r (s) = 0.717 on postoperative day 1; 0.716 on postoperative day 4), and overall performance category (r (s) = 0.642 on postoperative day 1; 0.702 on postoperative day 4) (P <.001). All animals in which oxygenated hemoglobin signal nadir time was less than 25 minutes were free of behavioral or histologic evidence of brain injury. CONCLUSION: Oxygenated hemoglobin signal nadir time determined by near-infrared spectroscopy monitoring is a useful predictor of safe duration of circulatory arrest. Safe duration of hypothermic circulatory arrest is strongly influenced by perfusate hematocrit value and temperature during circulatory arrest.

Analysis of Variance↗

PubMed2001

Different vulnerability of rat retinal cells to methylmercury exposure.

We tested the hypothesis that methylmercury chloride (MMC) caused a selective vulnerability in rat retinal cells during the intact preparation. MMC was injected subcutaneously daily at 3 different doses (0.25, 0.70 or 1.50 mg/kg/day) for 30 days. The electroretinograms under dark- and light-adaptation were recorded before and at 10-day intervals during the treatment period. With the lowest dose of MMC, only the amplitude of the light-adapted (LA) 20 Hz response significantly decreased on Day 30. At the intermediate dose, amplitude reductions were observed on Day 20 for the LA 20 Hz response and dark-adapted (DA) a-wave, while reductions in the LA 2 Hz b-wave and DA b-wave were noted only on Day 30. At the highest dose, these changes occurred earlier during the course of treatment. However, the amplitude of the DA second positive oscillatory potentials and the implicit times of any response components remained unchanged at all dosages. These results suggest that the cones are more sensitive than the rods, bipolar cells and Müller cells to MMC. However, amacrine cells were found to be relatively insensitive. Therefore, each retinal cell was found to have a different vulnerability to MMC.

Amacrine Cells↗

PubMed2001

Suppressive effect of nitrous oxide on motor evoked potentials can be reversed by train stimulation in rabbits under ketamine/fentanyl anaesthesia, but not with additional propofol.

The effect of nitrous oxide on myogenic motor evoked potentials (MEPs) after multipulse stimulation is controversial. We investigated the effects of propofol in this paradigm. MEPs were elicited electrically by a single pulse and by trains of three and five pulses in rabbits anaesthetized with ketamine and fentanyl. Nitrous oxide 30-70% was given and MEPs were recorded. After washout of nitrous oxide, propofol was given as a bolus of 10 mg kg(-1) followed by 0.8 (n=9) or 1.6 mg kg(-1) min(-1) (n=8) as a continuous infusion. Nitrous oxide was then re-administered and MEPs were recorded. Without propofol, nitrous oxide significantly reduced the amplitude of MEPs dose-dependently, but this effect was reversed by multipulse stimulation. Administration of low-dose propofol enhanced nitrous oxide-induced suppression, and this effect was reversed by five-pulse stimulation. However, high-dose propofol produced a greater increase in suppression, such that even five-pulse stimulation did not overcome the suppression. The results suggest that the degree of reversal of nitrous oxide-induced MEP suppression produced by multipulse stimulation is affected by the administration of propofol.

Anesthetics, Combined↗

PubMed2001

Amrinone can accelerate the cooling rate of core temperature during deliberate mild hypothermia for neurosurgical procedures.

We investigated the effects of i.v. amrinone on intraoperative changes of core temperature during deliberate mild hypothermia for neurosurgery. The patients in a control group (n=10) did not receive amrinone and patients in the amrinone group (n=10) received amrinone 5 microg kg(-1) min(-1) after a loading dose of 1.0 mg kg(-1). Anaesthesia was maintained with nitrous oxide in oxygen, propofol and fentanyl. After the induction of anaesthesia, patients were cooled and tympanic membrane temperature was maintained at 34.5 degrees C. After completion of the main surgical procedures, patients were rewarmed in the operating room. Tympanic membrane temperatures between 30 and 90 min after cooling were significantly lower in the amrinone group than in the control group. During cooling, the times taken to cool to 35 degrees C and to the lowest temperature were significantly shorter in the amrinone group than in the control group. These results suggest that i.v. amrinone can accelerate the cooling rate of core temperature during deliberate mild hypothermia for neurosurgical procedures.

Amrinone↗

PubMed2001

Study on structure of ribosomal RNA by time-resolved luminescence anisotropy analysis.

Evaluation of the folded structure of E.coli 16S-rRNA was performed using 5'-Ru(II) complex labeled oligodeoxyribonucleotide (Ru-probe) as the probe. This probe could evaluate the dynamic manner of the binding site of Ru-probe by using the time-resolved luminescence anisotropy technique. It was found that the rotational manner of Ru-probe in the presence of 16S-rRNA was markedly dependent on the oligonucleotide sequence, indicating that the microenvironments around the Ru-probes were largely different.

Anisotropy↗

PubMed2001

The mechanism to suppress photosynthesis through end-product inhibition in single-rooted soybean leaves during acclimation to CO(2) enrichment.

Single-rooted soybean leaves were used to investigate the suppression of photosynthesis through end-product inhibition during acclimation to CO(2 )enrichment. The photosynthetic activity was greater in leaves cultured at a CO(2) partial pressure of 70 Pa (high-CO(2)) than that in the leaves cultured at 35 Pa CO(2) (control) during the initial exposure to CO(2) enrichment but then decreased rapidly with a large accumulation of starch, to well below the level of the control leaves. The response curve of photosynthesis (A) to the intercellular CO(2) concentration (Ci) in the high-CO(2) leaves cultured long-term exhibited a significantly low initial gradient. However, on exposure to darkness for 48 h, the initial gradient of the A to Ci curve and rate of photosynthesis were completely restored, and almost all of the accumulated starch was expended. The ribulose bisphosphate carboxylase (RuBPcase) content and activation ratio in the high-CO(2) leaves remained high and roughly constant during the experiment, and were unchanged by the exposure, while this enzyme was slightly inactivated or inhibited after long-term exposure to CO(2) enrichment. The lower rate of photosynthesis in the high-CO(2) leaves could be linearly increased to a rate approaching the control level by increasing the external atmospheric [CO(2)], which thereby compensated for a reduced CO(2) transfer diffusion from the intercellular space to the stroma in chloroplasts. It is consequently concluded that, during the acclimation to CO(2 )enrichment, the suppression of photosynthesis through end-product inhibition was mainly caused by a lowering of the carboxylation efficiency of RuBPcase due to hindrance of CO(2) diffusion from the intercellular space to the stroma in chloroplasts brought about by the large accumulation of starch.

Adaptation, Physiological↗

PubMed2001

The association of high jugular bulb venous oxygen saturation with cognitive decline after hypothermic cardiopulmonary bypass.

UNLABELLED: This study was conducted to investigate whether jugular bulb venous oxygen saturation (SjVO(2)) predicted cognitive decline after cardiac surgery with hypothermic cardiopulmonary bypass (CPB). We studied 35 patients undergoing cardiac surgery. After the induction of anesthesia, a 5.5F fiberoptic oximetry catheter was retrogradely inserted into the jugular bulb, and SjVO(2) and other cerebral oxygenation variables were analyzed before, during, and after CPB. At each point, an oxyhemoglobin dissociation curve was drawn, and the P(50) value of jugular bulb venous blood was calculated by computer analysis. Cognitive function was assessed with the revised version of Hasegawa's Dementia Scale and the Benton Revised Visual Retention Test before and early after the operation. In 15 patients (the Decline group), cognitive function was declined after surgery, whereas it remained unchanged in 20 patients (the Normal group). SjVO(2) was significantly higher and cerebral oxygen extraction was significantly lower before and during CPB in the Decline group than in the Normal group (P < 0.05). The oxygen pressure at an oxygen saturation of 50% was significantly lower before and after CPB in the Decline group than in the Normal group (P < 0.05). Logistic regression analysis showed that high SjVO(2) was a predictor of cognitive decline after cardiac surgery. We conclude that high SjVO(2) was associated with cognitive decline after cardiac surgery with hypothermic CPB. IMPLICATIONS: Jugular bulb venous oxygen desaturation has been suggested as a predictor of cognitive decline after cardiac surgery. However, the clinical value of jugular bulb venous oxygen saturation (SjVO(2)) may be limited during hypothermic cardiopulmonary bypass (CPB) when oxygen affinity to hemoglobin is increased. This study shows that high SjVO(2) before and during hypothermic CPB is a predictor of subsequent cognitive decline.

Adult↗

PubMed2001

Catecholamines play a role in the production of interleukin-6 and interleukin-1alpha in unburned skin after burn injury in mice.

OBJECTIVE: To investigate the effects of catecholamines on the production of interleukin (IL)-6 and IL-1alpha in unburned skin after a burn injury. DESIGN: Randomized, controlled study. SETTING: Animal laboratory. SUBJECTS: Anesthetized female C57BL/6 mice. INTERVENTIONS: A full-thickness burn injury on 20% of total body surface area was produced on the clipped dorsum, which was followed by resuscitation with lactated Ringer's solution (0.1 mL/g). Phentolamine mesylate (10 mg/kg) or propranolol hydrochloride (10 mg/kg) was administered intraperitoneally before the burn injury. MEASUREMENTS AND MAIN RESULTS: Epinephrine and norepinephrine increased the production of IL-6 but not of IL-1alpha in normal abdominal skin, and these increases were reversed by a beta-blocker (propranolol hydrochloride) but not an alpha-blocker (phentolamine mesylate). A 20% full-thickness burn injury of the skin increased the plasma concentration of epinephrine 30 mins after the injury in female C57BL/6 mice, but not norepinephrine or dopamine. The burn also increased IL-6 production in unburned abdominal skin. The administration of a beta-blocker before a 20% burn injury suppressed the increased IL-6 production in unburned abdominal skin as determined by both protein level and mRNA expression. Pretreatment with the alpha-blocker was less effective. CONCLUSIONS: We propose that the neuroendocrine system activated by a 20% burn injury participates in the increased IL-6 production in the unburned skin.

Adrenergic alpha-Antagonists↗

PubMed2001

Effect of mild hypothermia on nicorandil-induced vasodilation of pial arterioles in cats.

OBJECTIVE: Nicorandil is characterized as hybrid between nitrates and potassium channel activators. Recent evidence suggested that mild hypothermia may alter cerebral vasodilation induced by a nitrate agent and potassium channel opener. However, the effect of mild hypothermia on nicorandil-induced vasodilation is not known. The present study was conducted to investigate whether mild hypothermia could alter nicorandil-induced cerebral vasodilation. In addition, the effects of mild hypothermia on cerebral vasodilation induced by nitroglycerin, a nitrate agent, and cromakalim, a selective adenosine 5'-triphosphate-sensitive potassium channel opener, were assessed in the same model. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-four cats. INTERVENTIONS: Animals were anesthetized with pentobarbital. The cranial window technique, combined with microscopic video recording, was used to measure small (50-100 microm) and large (100-200 microm) pial arteriolar diameter in an experiment. Animals were assigned randomly to either a normothermic (37 degrees C) or a hypothermic (33 degrees C) group. Nicorandil, nitroglycerin, or cromakalim at concentrations of 10(-8), 10(-6), or 10(-4) mol/L was applied topically in the cranial window, and the diameter of pial arterioles was measured. MEASUREMENTS AND MAIN RESULTS: Topical administration of nicorandil, nitroglycerin, and cromakalim significantly dilated both small and large pial arterioles in a dose-dependent manner during normothermia. Nicorandil-induced vasodilation of either large or small pial arterioles was not affected by hypothermia. However, hypothermia significantly attenuated nitroglycerine-induced vasodilation in both large and small pial arterioles and enhanced cromakalim-induced vasodilation in both large and small pial arterioles. CONCLUSIONS: Nicorandil-induced vasodilation of cerebral pial arterioles was not affected by mild hypothermia. By contrast, mild hypothermia significantly attenuated nitroglycerin-induced vasodilation and enhanced cromakalim-induced vasodilation.

Administration, Topical↗

PubMed2001

Effects of blockade of the renin-angiotensin system on tissue factor and plasminogen activator inhibitor-1 synthesis in human cultured monocytes.

OBJECTIVES: To clarify the pathophysiological significance of the renin-angiotensin system (RAS) in monocytes, we examined the effect of its blockade on tissue factor and plasminogen activator inhibitor-1 (PAI-1) synthesis in human cultured monocytes. METHODS: Monocytes were isolated from healthy volunteers and cultured. Tissue factor and PAI-1 antigens in culture medium and cells were measured by enzyme-linked immunosorbent assay and Western blotting, and mRNA levels were assessed by reverse-transcriptase polymerase chain reaction. RESULTS: We show that the RAS is present in isolated human peripheral blood monocytes. Exogenous angiotensin II increased the levels of tissue factor antigen and mRNA in cultured monocytes, but not of PAI-1 synthesis. An angiotensin converting enzyme (ACE) inhibitor (captopril) and an angiotensin II type 1 (AT1) receptor antagonist (candesartan) decreased the levels of tissue factor protein and mRNA in cultured monocytes. These alterations were accompanied by a reduction in the levels of tumour necrosis factor-alpha protein and mRNA. The levels of PAI-1 protein were reduced by captopril, but not by candesartan. A bradykinin B2 receptor antagonist abolished the suppressive effect of captopril on PAI-1 antigen. CONCLUSIONS: An ACE inhibitor and an AT1 receptor antagonist reduced tissue factor synthesis in these cells. We show different actions of these agents on PAI-1 synthesis. ACE inhibition decreased PAI-1 synthesis mediated by bradykinin production, but AT1 receptor inhibition had no effect.

Angiotensin II↗