摘要:

SUMMARY1.In vitrotime course studies on the effects of hexamethonium (7 mmol/L), pancuronium (5 μmol/L) and decamethonium (220 μmol/L) on nerve‐evoked (2 Hz for 2 s every 20 s) maximal twitches (T1, T2, T3, T4) of the rat hemidiaphragm were conducted. All three drugs progressively depressed all four twitches in a given train but at different rates (T4>T3>T2≫ T1).2. The response‐time profiles for T1and T4varied widely for the three drugs such that, for the same degree of T1‐block, each drug produced a different magnitude of T4‐block during the onset of and recovery from neuromuscular blockade.3. Analysis of the T1versus T4/T1plot showed that, at 50% T1‐block, the corresponding T4/T1(i.e. train‐of‐four ratios) during the onset (and recovery) phase were 0.16 (0.29), 0.46 (0.40) and 0.66 (0.53) for hexamethonium, pancuronium and decamethonium, respectively. Thus, for the same degree (i.e. 50%) of twitch (T1) tension depression, the three drugs differed widely in their ability (hexamethonium ≫ pancuronium>decamethonium) to produce fade as reflected in the respective train‐of‐four ratio.4. Our results therefore show that the train‐of‐four ratio (T4/T1) at 50% T1‐block obtained from suchin vitrotime course studies is a useful quantitative index of the potential of various drugs to cause train‐of‐four fade. Based on this index a classification of various compounds already studied is proposed as follows: hexamethonium ≫ pancuronium ∼ (+)‐tubocurarine>decameth

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb02400.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. Rat isolated atria were incubated with3H‐noradrenaline and the intramural sympathetic nerves were stimulated at 2 Hz for 60 s. The stimulation‐induced (SI) efflux of radioactivity was used as an index of release of transmitter noradrenaline.2. Isoprenaline (0.1 μmol/L) alone did not increase noradrenaline release. Cocaine (30 μmol/L) produced a 73% increase in the stimulation‐induced release of noradrenaline. In the presence of cocaine, isoprenaline enhanced noradrenaline release by 22%.3. In the presence of cocaine, both angiotensin I (0.3 μmol/L) and angiotensin II (0.3. μmol/L) produced almost two‐fold enhancements in the SI release of noradrenaline.4. Captopril (5 μmol/L) blocked the facilitatory effect of angiotensin I on nor‐adrenaline release but did not alter that of isoprenaline.5. Saralasin (0.1 μmol/L) reduced the facilitatory effect of angiotensin II on noradrenaline release but did not alter that of isoprenaline.6. The findings indicate that the facilitation of noradrenaline release by isoprenaline in rat atria is not mediated by local formation of

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb02401.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. The disposition of diflunisal (DF) was investigated in both bile‐exteriorized and intact rats given 10 and 100 mg/kg doses intravenously (i.v.).2. In addition to the phenolic glucuronide (DPG) and acyl glucuronide (DAG) conjugates, the sulfate conjugate (DS) was found to be a major metabolite. The glucuronides were excreted preferentially in bile, whereas DS was excreted almost exclusively in urine.3. In bile‐exteriorized animals, recoveries of DPG, DAG and DS in bile were 12.2%, 23.8%, 0.4%, respectively, and in urine, 10.3%, 5.6% and 15.2%, respectively, at the 10 mg/kg dose; and in bile, 11.3%, 41.6% and 1.0% respectively, and urine 2.9%, 1.1% and 17.0%, respectively, at the 100 mg/kg dose.4. Total plasma clearance of DF and formation clearance of DF to DPG were reduced at the higher dose, suggesting saturation of this glucuronidation pathway. Formation clearances of DF to DAG and DS were little affected by the dose change.5. Considerable enterohepatic recirculation of DF was apparent from the prolongation of DF and its conjugates in plasma of rats with an intact bile flow into the gut. The net metabolic effect of such cycling was enhancement of overall DS formation, from 15.6% and 18.0% of the 10 and 100 mg/kg doses, respectively, in bile‐exteriorized rats to 28.5% and 42.1% of the doses respectively, in the intact an

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb02402.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. The effects of hypoxia, histamine‐receptor agonist perfusion, and their combination on cardiac rhythm were studied in isolated rat hearts.2. While hypoxia induced a high incidence of ventricular tachycardia or fibrillation, only a few preparations developed ventricular arrhythmias in response to perfusion with high concentration of histamine, 2‐pyridylethylamine or impro‐midine.3. The times of onset of hypoxia‐induced ventricular arrhythmias were significantly shortened by perfusion with either histamine, 2‐pyridylethylamine or impro‐midine. The accelerated occurrence of hypoxia‐induced ventricular arrhythmias by histamine was significantly abolished by pretreatment with either diphenhydramine or cimetidine.4. The results indicate that hypoxia and histamine can increase ventricular vulnerability of the rat heart to each other. It is also suggested that the arrhythmogenic actions of histamine in hypoxic rat hearts are mediated by both histamine H1‐ a

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb02403.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. The nitric oxide (NO) synthesis inhibitor NG‐monomethyl‐l‐arginine (l‐NMMA), but notd‐NMMA, inhibited the NANC‐mediated relaxations of the rat anococcygeus muscle, but did not affect the relaxation produced by sodium nitroprusside.2. The inhibitory effect ofl‐NMMA was reversed byl‐arginine but not byd‐arginine, and prior exposure tol‐arginine blocked the effect ofl‐NMMA.3. The noradrenergically mediated contractions of the anococcygeus elicited by field stimulation were slightly enhanced byl‐NMMA, but the response to noradrenaline was not affected.4. The results suggest that NANC transmission in the rat anococcygeus muscle involves the generat

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb02404.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. A biventricular, low‐output congestive cardiomyopathy was induced in 19 rabbits by administering adriamycin (16 mg/kg). The effects of SaL‐rat atrial natriuretic peptide (ANP) infused at 0.1, 0.2 and 0.4 μg/kg per min, were then examined in terms of (i) central haemodynamics (ii) regional blood flow (iii) renal function and (iv) plasma norepinephrine and plasma renin.2. In this dose range, ANP produced progressive and significant falls in stroke volume, cardiac output and mean arterial pressure, owing to a fall in venous return. The heart rate response to this was blunted.3. Using radiolabelled microspheres, significant falls in the perfusion of cutaneous, gastrointestinal and musculoskeletal tissues were observed, due to reduced vascular conductances in these beds. These changes were accompanied by activation of the sympathetic nervous system as evidenced by a progressive rise in plasma norepinephrine. A significant increase in plasma renin was only observed with the highest infusion of ANP.4. Renal blood flow was maintained in the face of a falling mean arterial pressure and cardiac output, but diuretic and natriuretic effects were absent.5. It was concluded that the dominant influence of ANP infusion in this model of heart failure appeared to be a reduction in cardiac preload with detrimental overall haemodynamic conseque

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb02405.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb02406.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY