摘要:

Using a peroxide-injured endothelial cell model, beraprost sodium (beraprost) was tested in relation to the action to protect against the damage of vascular endothelial cells employing the viability of the cells and change in lipid peroxides as the indicators. At a concentration of 1-3 µmol/l or higher, beraprost significantly inhibited the decrease in viability of the cells and the increase in lipid peroxides level caused by t-butyl hydroperoxide or 15-hydroperoxy-5,8,1113-eicosatetraenoic acid. When similar tests were conducted with prostaglandin I2, its inhibiting action was equal to or slightly weaker than that of beraprost unlike PGE1 and PGD2. This action of beraprost in inhibiting cell damage caused by peroxides suggests that beraprost may be useful for protecting cells from damage due to ischemic diseases

ISSN:0031-7012    

DOI:10.1159/000138981

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The cardioprotective effects of the K channel activator drugs celikalim (WAY-120,491) and cromakalim were studied in a canine model of myocardial infarction consisting of 90 min of ischemia and 5 h of reperfusion. Intracoronary infusion of cromakalim and celikalim at 0.2 µg/kg/min beginning 10 min before occlusion of the left circumflex coronary artery and continuing throughout the duration of the reperfusion period appeared to exacerbate ischemic injury. Infarct size (percent of risk area) was 27.7 ± 5.6% in vehicle control animals (n = 5), 40.3 ± 6.2% for cromakalim (n= 5) and 55.7 ± 6.4% (p < 0.05 vs. vehicle) for celikalim-treated animals (n = 5). When these compounds were administered intravenously, using doses shown to increase total coronary flow in nonoccluded control animals, no exacerbation of ischemic injury was observed. Anatomic infarct size was 32.8 ± 7.1 % for vehicle animals (n = 5) and 32.6 ± 13.3 and 30.9 ± 9.8% for cromakalim- (n = 6) and celikalim-treated (n = 5) animals, respectively. Intravenous diltiazem decreased myocardial infarct size to 16.3 ± 7.3% (n = 5) of area at risk (p = NS vs. vehicle). The anatomic area at risk was similar in all three treatment groups, and no significant differences in rate-pressure product were observed. Results of this study suggest that K-channel-activating drugs such as cromakalim and celikalim may not be effective agents in the acute therapeutic management of myocardial ischemic

ISSN:0031-7012    

DOI:10.1159/000138982

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The influence of acetaldehyde (30 mg/kg i.v.) on blood pressure and heart rate in anesthetized and pithed rats was studied. In anesthetized rats we observed a small increase, and a subsequent considerable decrease in mean blood pressure. The latter did not occur in pithed rats. Stimulation of the circulatory system in anesthetized and in pithed rats was completely abolished by administration of phentolamine or reserpine. Both in anesthetized and in pithed rats acetaldehyde caused an increase in heart rate which was inhibited in animals treated earlier with propranolol or reserpine. Our results demonstrated that besides its peripheral action, acetaldehyde exerts central effects which cause severe hypotension.

ISSN:0031-7012    

DOI:10.1159/000138983

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The effect of diabetes mellitus on intracellular calcium concentration was measured in single rat bladder smooth muscle cells using the fluorescent calcium indicator dye fura-2 AM. Techniques were developed for isolation and short-term culture of rat bladder smooth muscle cells. Cytosol-free calcium concentrations were measured at rest and during carbachol stimulation. Peak intracellular calcium concentration, rate of increase in intracellular calcium concentration and the integral of accumulation of intracellular calcium were determined. The techniques used to isolate and culture bladder smooth muscle cells produced live, physiologically responsive cells. Resting intracellular free calcium levels and were similar in control and diabetic cells. Both control and diabetic cells responded to carbachol stimulation. No significant differences between these cells were noted in peak calcium concentrations, rate of response or integral of response, but standard errors were large. Two patterns of intracellular response to carbachol stimulation were identified, and may explain the large variability in intracellular calcium response to carbachol stimulation.

ISSN:0031-7012    

DOI:10.1159/000138984

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

This study examined contractile responses of the in vitro rabbit whole-bladder preparation to field stimulation, bethanechol and KCl in Tyrode’s solution and minimum essential medium (MEM). We found frequency-dependent increases in intravesical pressure in bladders incubated in Tyrode’s solution and MEM. However, bladders incubated in MEM consistently responded with greater increases in intravesical pressure compared to those incubated in Tyrode’s solution. Similarly, there were frequency-dependent increases in the rate of pressure generation in bladders incubated in Tyrode’s solution and MEM, and bladders incubated in MEM responded with greater rates of pressure generation than those incubated in Tyrode’s solution at frequencies of 1 2 and 4 Hz. In addition, there were significant increases in intravesical pressure generated in response to administration of 500 mmol/l bethanechol and 186.4 mmol/l KCl in bladders incubated in MEM compared to Tyrode’s solution but no changes in the rate of pressure generation. The influence of L-methionine, one of the constituents of MEM, on the responses of whole bladders to nerve stimulation was also investigated. L-methionine at concentrations of 0.1 and 1.0 mmol/l had no effects on the increase in intravesical pressure or rate of pressure generation following nerve stimulation. It is speculated that the increases in contractile responsiveness of bladders incubated in MEM are related to the combination of amino acids, vitamins and other constituents of the cell cul

ISSN:0031-7012    

DOI:10.1159/000138985

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The present study investigated the protective effects of the new potent synthetic protease inhibitors, ONO3307 (4-sulfamoyl phenyl-4-guanidinobenzoate methanesulfonate) and FOY007 (gabexate misilate), on the exocrine pancreas in rat caerulein-induced acute pancreatitis in both in vitro and in vivo experiments. These protease inhibitors prevented hyperamylasemia, pancreatic edema, congestion of amylase, redistribution of lysosomal enzyme in acinar cells, and lactic dehy-drogenase (LDH) discharge from dispersed acini. They also inhibited the cathepsin B leakage from the lysosomes in a dose-dependent manner in doses of 2–10 mg/kg·h of ONO-3307 and 20-50 mg/kg·h of FOY007. These results indicate that both ONO3307 and FOY007 exert protective effects against pancreatitis at subcellular levels in lysosomes and cellular or organelle membranes. Proteases appear to be important in the pathogenesis and development of acute pancreatitis, and low-molecular-weight protease inhibitors may be of clinical use in the treatment of acute pancreati

ISSN:0031-7012    

DOI:10.1159/000138986

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Ryanodine is a pharmacological agent that stimulates calcium leakage into the cytoplasm resulting in an increase in tension. In skeletal muscle, ryanodine acts primarily on the sarcoplasmic reticulum whereas in smooth muscle, the sites of action are less clear. Visually, the increase in tension is slow and the time course can be mimicked by mitochondrial poisoning and the resultant leak of mitochondrial calcium into the cytoplasm. Although it has been reported that ryanodine has no effect on calcium flow into or from mitochondria, the effect of ryanodine on mitochondrial oxidative function was not studied. In the current investigation direct measurements of the effect of ryanodine on mitochondrial oxygen utilization were made. The results demonstrate that ryanodine, even at high concentrations, has no effect (stimulatory or inhibitory) on mitochondrial oxidation.

ISSN:0031-7012    

DOI:10.1159/000138987

出版商:S. Karger AG    

年代:1992

数据来源: Karger