摘要:

To shed light on the role of thromboxane A2 (TXA2) in renal injury, we evaluated the effects of S-1452, a TXA2 receptor antagonist, on rats with streptozotocin (STZ)-induced diabetic nephropathy and murine lupus nephritis. In STZ diabetes rats (n = 6), urinary protein excretion significantly increased from 8 weeks and was about 5 times as much as that in normal rats at 10 weeks after induction of diabetes. In S-1452-treated rats (n = 6), increase in urinary protein was rarely observed and was significantly inhibited at 8 and 10 weeks after induction of diabetes. In (NZB × NZW)F1 mice, no proteinuria was detected in vehicle controls (n = 20) and S-1452-treated mice (n = 20) from 0 to 8 weeks after initiation of S-1452 treatment. Proteinuria was observed in 3, 7 and 8 mice in the control group, and 0, 2 and 5 mice in the S-1452 group at 12, 16 and 20 weeks after initiation of S-1452 treatment, respectively. Proteinuria developed more slowly in S-1452-treated mice than in vehicle controls. In conclusion, TXA2 receptor antagonist, S-1452, suppresses the progression of renal injury

ISSN:0031-7012    

DOI:10.1159/000139261

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Infusion (0.46 µmol/kg/min) of the endothelin (ET)-converting-enzyme inhibitor, phosphoramidon (P), protected function and structure after 30 min renal ischemia in rats more than treatment (5 µmol/kg/min) with the ETA receptor antagonist, BMS-182874 (B). The glomerular filtration rate (GFR; 0.7 ± 0.12 ml/min) and renal plasma flow (RPF) decreased approximately 40% at 2h reflow versus controls (C: 1.2 ± 0.12). B weakly protected the GFR (0.8 ± 0.07 ml/min); P restored it (1.1 ± 0.05). Both compounds reduced tubular injury at 2 h reflow; P ameliorated glomerular changes. At 24 h the GFR (0.6 ± 0.06 ml/min) and RPF decreased 67% versus C (1.8 ± 0.08). B did not protect the GFR and RPF. P partially protected the GFR (0.9 ± 0.07 ml/min) but not RPF, and reduced tubular injury. The results suggest that both ETA and non-ETA receptors mediate ET-induced changes in ischemic renal

ISSN:0031-7012    

DOI:10.1159/000139262

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

This study was performed to assess the effect of BMY21190, an inhibitor of cAMP phosphodiesterase, on infarct size using a canine ischemic model that underwent a 90-min occlusion and a 6-hour reperfusion of the left coronary artery. The infarct zone/area at risk of the BMY21190 group was significantly smaller than that of the vehicle group (36.1 ± 7.8%; 62.4 ± 4.3%, respectively; p < 0.05). Myeloperoxidase activity, an indicator of neutrophil infiltration, was significantly correlated to infarct size (r = 0.6893, p < 0.02). Myeloperoxidase activity (0.14 ± 0.07 U/100 mg tissues) measured in the area at risk from hearts of the BMY21190-treated group was significantly lower than that of the vehicle-treated tissue (0.40 ± 0.08 U/100 mg tissue, p < 0.05). It is suggested that BMY21190 reduces infarct size through the inhibition of neutrophil infiltration in the canine mo

ISSN:0031-7012    

DOI:10.1159/000139263

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

In a model of volume-controlled hemorrhagic shock causing the death of all control animals within 30 min, the intravenous injection of nicotine produced a rapid, sustained and dose-dependent restoration of cardiovascular and respiratory functions, with 60 and 100% survival 2 h after the administration of 3 and 12 µg/kg, respectively. An effect similar to that of the highest dose of nicotine were obtained with the intravenous bolus injection of ACTH(l-24) at the dose of 160 µg/kg. However, the ACTH plasma levels of hemorrhage-shocked rats treated with nicotine was not different from that of hemorrhage-shocked rats treated with saline, thus excluding the possibility that nicotine-induced shock reversal may be due to the massive release of ACTH. Since in rats pretreated with cycloheximide at a dose (20 mg/kg intraperitoneally) causing an 82% inhibition of protein synthesis, and then bled to hemorrhagic shock, the effect of nicotine was greatly reduced (only the dose of 50 µg/kg producing 100% survival 2 h after treatment), protein synthesis, however, seems to be important for the effect of nicotine in hemorrhagic shock, at least at the lowest dos

ISSN:0031-7012    

DOI:10.1159/000139264

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

To determine whether the peripheral opioid system participates in hypertension development we studied responses to various opioid receptor agonists in field-stimulated isolated tail artery segments taken from spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats at different ages. The µ-selective agonist (DAGO) and the δ-selective D-Ala2-D-Leu5-enkephalin (DADLE) both suppressed the electrically stimulated vaso-constriction (EIC), but only in SHR arteries. The µ-selective antagonist β-funaltrexamine reversed the effects of both DAGO and DADLE. Since the δ-selective antagonist ICI-174864 did not block DADLE inhibition, it is likely that both DAGO and DADLE effects were µ-receptor-mediated. Effects of DAGO and DADLE were qualitatively and quantitatively similar at all ages of SHR tested, and were not temporally related to hypertension development. Dynorphin (1-13) (DYN), a ĸ-agonist, increased basal tone and EIC in all three rat strains. These responses were not blocked by nor-binaltorphimine, a selective ĸ-opioid antagonist, suggesting that they may not involve K-receptor activation. There was a greater sensitivity to DYN at younger ages in all three rat strains and the sensitivity decreased with age. At 16 weeks when SHR hypertension was fully developed, SHR tail artery became almost totally insensitive to DYN in contrast to the continued responsiveness of 16-week-old WKY and SD arteries. The diminished effects to DYN in 16-week-old SHR tail arteries is suggestive of a compensatory mechanism to the hypertensive state. Collectively, the results establish that opioid receptor responses in SHR tail artery differ from those of normotensive rats. The significance of these differences to hypertension development in SHR remains to be det

ISSN:0031-7012    

DOI:10.1159/000139265

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Both in vivo and in vitro exposure to morphine have been reported to produce a number of immunomodulatory effects in both laboratory animals and humans. The current study was performed to assess the direct in vitro effect of exposure to morphine or morphine metabolites on immune response parameters. Murine B6C3F1 splenic lymphocytes or peritoneal macrophages were cultured in vitro at concentrations of 0.0001-100 µmol/l morphine sulfate, morphine-3-glucuronide, morphine-6-glucuronide, or normorphine. B cell proliferation was significantly suppressed following exposure to all drugs. Production of interleukin (IL)-2, IL·4, and IL·6 was affected only moderately by all drugs except morphine-6-glucuronide, which produced a marked suppression at 100 µmol/l. Both basal and augmented natural killer (NK) cell function were unaffected by any drug except morphine-6-glucuronide, which enhanced NK cell activity at concentrations between 0.0001 and 1.0 µmol/l. In contrast, both morphine-3-glucuronide and morphine-6-glucuronide significantly inhibited cytotoxic T lymphocyte induction at concentrations between 0.0001 and 100 µmol/l, whereas morphine and normorphine were inactive in this assay. In summary, in the absence of direct cellular cytotoxicity, a differential immunomodulation was observed following in vitro exposure to morphine and its metabo

ISSN:0031-7012    

DOI:10.1159/000139266

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The plasma pharmacokinetic profile of recombinant porcine growth hormone (rpGH) was studied in six healthy gilts after a rapid single i.v. injection of 250 µg/kg rpGH. The linear pharmacokinetic properties of rpGH were investigated by giving four different doses of the hormone at intervals of 2 days. The plasma rpGH concentration was determined by radioimmunoassay with a lowest detection limit of 50 pg/ml. Plasma levels of rpGH were fitted to a three-compartment open model; a triexponential decrease in plasma rpGH with a rather long mean terminal half-life of 40.22 ± 5.623 min was obtained in these pigs. Linear pharmacokinetic properties of rpGH were confirmed in the additional pig that received doses between 25 and 250 µg/kg rpGH. The small volume of distribution, 0.029 ± 0.003 1/kg, indicated that most of the injected rpGH was confined to the blood and probably lymph. The total plasma clearance of rpGH was 31.80 ± 2.802 ml/h × kg. The results not only contribute significantly to our knowledge about rpGH pharmacokinetics, but also to future studies for the rational design of optimal dosage regimens and the development of a controlled-release device for

ISSN:0031-7012    

DOI:10.1159/000139267

出版商:S. Karger AG    

年代:1995

数据来源: Karger