摘要:

The inhibitory effects of glycerol trinitrate (GTN) and diltiazem (DZ) on contractions produced by submaximal concentrations (ED 75) of norepinephrine (NE) and potassium chloride (KC1) were studied in isolated canine renal artery rings. In addition, the site of action of these compounds in blocking NE-induced contractions was determined by using zero calcium (Ca++) buffer + 2 mM EGTA (calcium-free solution). GTN was more potent than DZ in relaxing KCl-induced contractions (potential-operated calcium channels) as well as NE-induced contractions (receptor-operated calcium channels). In a Ca++-free buffer, the response to NE was reduced to approximately 20–25% of the response in normal Ca++ (1.25 mM) buffer. GTN (1 × 10–9–1 × 10–4M) produced a marked inhibition of NE-induced contractions in Ca++-free buffer, whereas DZ had no inhibitory effect even at very high concentrations (1 × 10–4M). Thus, GTN and DZ appear to interfere with different components of Ca++ entry through slow channels and intracellular Ca++ release. DZ primarily blocks the influx of Ca++ from the extracellular space, whereas GTN appears to act by inhibiting Ca++ movements at an intrac

ISSN:0031-7012    

DOI:10.1159/000138146

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Effects of diltiazem on isolated ureter and coronary artery of the dog were compared with those of glycerol trinitrate (GTN). Diltiazem (DZ) (10–9–10–6M) decreased the force and frequency of ureteral rhythmic contractions evoked by potassium or phenylephrine in a concentration-dependent manner, and relaxed potassium-contracted coronary artery strips. The dose dependence of the inhibitory effects of diltiazem was similar on the ureter and coronary artery. GTN (10–7–10–5M) also showed similar inhibitory effects, but these were more pronounced on the coronary artery than on

ISSN:0031-7012    

DOI:10.1159/000138147

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Six dogs were, under constant environmental conditions, treated for 7 weeks with clonazepam (0.5 mg/kg b.i.d. orally). Already after 1 week of treatment, slight symptoms of withdrawal could be elicited by intravenous injection of flumazepil (Ro 15-1788). When clonazepam was finally withdrawn, a self-limiting abstinence syndrome was observed in all dogs, consisting of behavioral alterations (listlessness, wet dog shakes, dorsal recumbency), tremor, a severe clonic-tonic seizure in 1 case, hyperthermia, and weight loss. The syndrome was most pronounced on days 2 and 3 after withdrawal, after 1 week all signs of physical dependence had disappeared.

ISSN:0031-7012    

DOI:10.1159/000138148

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Hypothalamic monoamine metabolism was evaluated in male and female mice that were administered monosodium glutamate (MSG, 4 mg/g) on postnatal day 4. Hypothalamic dopamine (DA) content was reduced approximately by 22% across all experiments and pituitary DA content was also significantly decreased. Despite reductions in hypothalamic DA levels, MSG-treated mice did not exhibit significant reductions in the levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Hypothalamic monoamine and metabolite profiles in MSG-treated and control mice were examined after the administration of pargyline (PAR), α-methyl-p-tyrosine (MPT) or reserpine (RES). DA turnover as indexed by PAR and MPT techniques were not as conclusive as the metabolite measures in suggesting an accelerated DA utilization. MSG-treated mice were more resistant to the DA-depleting actions of reserpine than were the controls. No alterations were found in hypothalamic norepinephrine metabolism in MSG-treated mice, however, after drug challenges, alterations were found in serotonin metabolism. These results indicate the extent and nature of the changes that occur in hypothalamic monoamine metabolism after neonatal MSG treatment. The DA neurons that survive MSG treatment appear to exhibit neurochemical characteristics dissimilar to those of tuberoinfun-dibular DA neurons. Additionally, the neuropharmacological actions of MPT, PAR and RES are discussed as they relate to hypothalamine monoamine metabolism in the mouse

ISSN:0031-7012    

DOI:10.1159/000138149

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

In vitro studies demonstrated that two selective monoamine oxidase (MAO)-A inhibitors, amiflamine and FLA 788(+), have been shown to inhibit semicarbazide-sensitive amine oxidase (SSAO) in rat testis and lung homogenates in a concentration-dependent way. The inhibition was not greatly influenced by pretreatment of the preparations with either clorgyline (10–3 mol/l), l-deprenyl (10–3 mol/l) or SKF 525A (10–4 mol/l). The two compounds showed a time-dependent inhibition of SSAO, and for the initial phase of the inhibition, amiflamine is a competitive inhibitor with a Kislope of 135 μmol/l, but FLA 788(+) is a noncompe-titive inhibitor with a Ki value of 180 μmol/l. After preincubation for 60 min at 37 °C, however, inhibition by amiflamine was found to be essentially irreversible whereas that produced by FLA 788(+) was still noncompetitive and reversible. These two compounds also reversibly and competitively inhibited rat testis MAO-A with FLA 788(+) being much more selective towards this MAO (Kislope = 0.26 μmol/l for FLA 788(+) and 7 μmol/l for amiflamine, respectively). The present results indicate that both MAO-A-selective inhibitors also inhibit SSAO in vitro, but their properties as SSAO inhibitors differ from those as MAO-A

ISSN:0031-7012    

DOI:10.1159/000138150

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

An anesthetic dose of 50 mg/kg (i.p.) sodium pentobarbital caused a 61% increase in blood glucose levels in mice. Nicotine (2.5 mg/kg) given intraperitoneally 15 min prior to the sodium pentobarbital treatment further increased hyperglycemia by 29% over pentobarbital alone and 90% higher than the control. Mecamylamine (0.5 mg/kg) given intraperitoneally 15 min prior to nicotine resulted in blood glucose concentrations near the control value. Atropine (2 mg/kg) administered intraperitoneally did not prevent the hyperglycemia induced by nicotine and pentobarbital. No significant correlation was observed between the sleep time and the blood glucose of the unconscious or awake mice. However, a significant correlation was observed between the blood glucose concentration of the sleeping and awake mice. Blood glucose levels were always higher when the neuronal activity was depressed and were lower when the neuronal activity was increased.

ISSN:0031-7012    

DOI:10.1159/000138151

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Proteinuria was diminished by concomitant oral administration of sorbinil, an aldose reductase inhibitor to streptozotocin-induced diabetic rats. Animals were placed in one of three groups: control, diabetic, sorbinil-treated diabetic. For a period of 10 weeks, 24-hour urine samples were analyzed weekly for volume, glucose, ketone, total protein (Pesce-Strande) and individual protein components having molecular weights between 15,000 and 120,000 daltons. The latter were examined by polyacrylamide gel electrophoresis and quantitated by laser densitometric analysis. Results indicated that controls excreted albumin (68,000 daltons) and low-molecular weight proteins between 15,000 and 20,000 daltons. Throughout the 10-week period of diabetes, there was a 7- to 12-fold increase in total urinary protein excreted in 24 h. Diabetic-induced proteinuria primarily resulted from excretion of newly detected proteins having molecular weights of 30,000–100,000 daltons and an increase amount of albumin. Sorbinil treatment prevented approximately 70% of the increase in total protein excretion despite persistent hyperglycemia, glycosuria and ketonuria. Laser densitometric analysis indicated that the aldose reductase inhibitor decreased by 70% the excretion of newly detected proteins and albumin while maintaining the 15,000- to 20,000-dalton proteins. These results suggest that the polyol pathway is implicated in diabetic-induced proteinuria and inhibition of aldose reductase may represent a therapeutic approach for management of diabetic nephropath

ISSN:0031-7012    

DOI:10.1159/000138152

出版商:S. Karger AG    

年代:1986

数据来源: Karger