摘要:

SUMMARY1. The effects of the Class I anti‐arrhythmic drugs quinidine, procainamide, lidocaine, phenytoin and tocainide on mitochondrial lactate dehydrogenase activity were compared in guinea‐pig heart preparations.2. All the tested drugs inhibited the enzyme activity in a concentration‐dependent fashion, exhibiting varying profiles in their actions. Lidocaine exhibited inhibitory concentration 20% (IC20) and IC50values of 0.52 ± 0.02 mmol/L and 25.6 ± 0.5 mmol/ L, procainamide 6.0 ± 0.2 mmol/ L and 108 ± 7.2 mmol/L, phenytoin 3.4 ± 0.06 μmol/L and 0.34 ± 0.02 mmol/L, quinidine 39.2 ± 1.2 μmol/L and 9.8 ± 0.8 mmol/L and tocainide 2.7 ± 0.3 mmol/L and 44.6 ± 2.5 mmol/L.3. According to the IC50values, this is the order of their inhibitory potencies: phenytoin>quinidine>lidocaine>tocainide>procainamide. This trend is in general agreement with the lipophilicity rank of the drugs.4. It is concluded, therefore, that inhibition of mitochondrial lactate dehydrogenase is a property shared by most Class I anti‐arrhythmic drugs which may depend on their lipophilicity and possibly their membrane

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01671.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. Isoprenaline and cardiac responsiveness of isolated atria from 2 and 6 week streptozotocindiabetic rats, and their age‐matched controls, was examined. The effects of chronic administration of epalrestat (40 mg/kg orally, by gavage) on diabetes‐induced changes were also investigated.2. Spontaneously beating atria, bathed in either normal or high glucose (30 mmol/ L) Krebs’ solution, from both 2 and 6 week diabetic rats beat more slowly and with greater force than atria from control rats. These changes in basal parameters were normalized by 2 weeks of insulin (5 U/day s.c.) treatment but not by 2 or 6 weeks of chronic treatment with epalrestat.3. Isoprenaline (0.1 nmol‐0.1 μmol/L) produced concentration‐dependent increases in inotropy and chronotropy in atria from both control and diabetic rats.4. Atria from 2 week diabetic rats displayed decreased sensitivity to the positive inotropic effects of isoprenaline. This change was normalized by chronic insulin treatment but not by chronic epalrestat treatment.5. Atria from 6 week diabetic rats displayed increased sensitivity to the positive chronotropic effects of isoprenaline which was normalized by epalrestat.6. These results suggest that changes observed in atria from 2 week diabetic rats may be due to hyperglycaemiaper sewhereas in atria from 6 week diabetic rats abnormal activity of the polyol pathway may be a contribut

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01672.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The activity of smooth muscle strips from normal and hypertrophied rat bladders was compared. The hypertrophied bladders were produced by partially obstructing the urethra 8–13 weeks previously.2. Spontaneous mechanical activity was more frequent and smaller in amplitude in strips from normal than hypertrophied bladders and was less sensitive to cromakalim, being reversibly abolished by cromakalim at 10−6mol/L compared with 10−7mol/L for hypertrophied bladder.3. The mean resting membrane potentials of smooth muscle cells from normal and hypertrophied rat bladders were ‐47.2 and ‐47.6 mV, respectively. Bursts of spontaneous action potentials, corresponding to the mechanical activity, were seen in some cells.4. Nifedipine at 10−6mol/L had no significant effect on the resting membrane potential. Occasional single spikes occurred with increased duration and the afterhyperpolarization was abolished. Cromakalim at 10−5mol/L produced hyperpolarization of 3–9 mV and, in the continued presence of the drug, occasional singe spikes could be recorded from both normal and hypertrophied bladders.5. Nifedipine at 10−6mol/L abolished movement but did not significantly alter [86Rb+] efflux from strips from either normal or hypertrophied bladders. Addition of cromakalim at 5± 10−6or 5 ± 10−5mol/L in the presence or absence of nifedipine increased efflux from the normal bladder by 30–40%. In the hypertrophied bladder the efflux increased by about 14% and 28% in the presence of 5 ± 10−6and 5 ± 10−5mol/L cromakalim, respectively.6. No significant differences between electrical properties of normal and hypertrophied bladders were therefore found and we are unable to explain why the mechanical activity of hypertrophied rat bladders was more sensitive to

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01673.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. Plocamadiene A is a polyhalogenated monoterpene, (1R, 2S, 4S, 1′E)‐2‐bromo‐l‐chloro‐4‐(2′‐chloroethenyl)‐I‐methyl‐5‐methylenecyclohexane, isolated from red marine algae of thePlocamiumgenus.2. This study examined the activity of plocamadiene A on guinea‐pig isolated ileum (GPI) and subsequently on rat isolated peritoneal mast cells.3. Plocamadiene A (1 μg/mL) produced a slow onset, sustained contraction of the GPI. This was insensitive to atropine (1 μmol/ L) and tetrodotoxin (1 μmol/ L), but was significantly reduced by H1‐histamine receptor antagonists including mepyramine (10 nmol/L), chlorcyclizine (10 nmol/L) and diphenhydramine (0.1 μmol/L). The H2‐histamine receptor antagonists cimetidine (0.1 μmol/L) and ranitidine (10 nmol/L) potentiated the response to plocamadiene A (1 μg/mL).4. The amplitude of contraction caused by plocamadiene A (1 μg/mL) gradually decreased when the compound was applied repeatedly to the GPI for 5 min every 10 min for 150 min.5. Contractions to plocamadiene A (1 μg/mL) were reduced to approximately 66% of the time control in ovalbumin‐sensitized GPI challenged with ovalbumin to release endogenous contractile agents.6. Cromolyn (0.1 mmol/ L) inhibited (by 40%) the response in the GPI caused by plocamadiene A (1 μg/mL) as compared with time controls.7. Spectrofluorometric assay suggested that both plocamadiene A (10 μg/mL) and compound 48/80 (10 μg/mL) caused histamine release from rat peritoneal mast cellsin vitro. This release of histamine was reduced by cromolyn (100 μg/mL).8. This study concluded that plocamadiene A releases histamine from mast cells of

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01674.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. Levels of peptidylglycine α‐amidating mono‐oxygenase (PAM) activity were examined in sheep and rat heart. This enzyme is responsible for α‐amidation of a large number of peptide hormones, a modification essential for the bioactivity of these peptides.2. PAM activity was measured in membrane and soluble fractions of atrial and ventricular homogenates by monitoring the amidation of iodinated synthetic substrate ([125I]‐Ac‐Tyr‐Val‐Gly).3. PAM activity in both species resided almost exclusively in the atria rather than the ventricles, and similar levels of activity were found in left and right atria. Membrane‐associated activity was 50‐to 100‐fold greater than soluble activity in the sheep, yet was only five‐ to 10‐fold greater in the rat, indicating a larger proportion of soluble enzyme in the rat atrium.4. Similar apparent Kmvalues were found for atrial membrane‐associated activity in both species (15.6 and 17.4 μmol/L for rat right and left atria, 16.7 and 15.6 μmol/L for sheep right and left atria); however, the maximum velocity (Vmax) levels were higher in the rat (40.5 and 43.9 pmol/μg per hvs12.8 and 15.1 pmol/μg per h).5. Because expression of many peptides and processing enzymes can be regulated by steroid hormones, the possible effects of chronic glucocorticoid administration (1 mg dexamethasone i.m. twice daily for 10 days) on PAM levels were tested in four sheep, with four sheep receiving saline only as controls. There was no discernible effect of dexamethasone on either the distribution or the kinetics of PAM activity in the sheep heart.6. This study demonstrates the presence of high levels of predominantly membrane‐associated amidating activity in sheep atria, and the failure of glucocorticoid treatment to alter this activity. The presence of abundant atrial PAM activity suggests the production of an amidated pepti

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01675.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The relaxant effects of brain natriuretic peptide (BNP) were investigated on guinea‐pig tracheal smooth muscle.2. Various amounts of BNP (10−9– 10−6mol/L) showed concentration‐dependent relaxant effects on resting tone, leukotriene D4(LTD4; 10−8mol/L) and endothelin‐1 (ET‐1; 10−8mol/L) induced contraction of tracheal smooth muscle with EC50values of 3.1± 0.7 ± 10−8, 3.9 ± 1.0 ± 10−8and 3.5 ± 1.0 ± 10−8mol/L, respectively.3. BNP increased tissue cyclic GMP levels in tracheal smooth muscle concentration dependently (187 ± 26 fmol/mg protein in control, 334 ± 77 fmol/mg protein at 10−8mol/L, 680 ± 54 fmol/mg protein at 10−7mol/L, 2162 ± 133 fmol/mg protein at 10−6mol/L).4. With the addition of BNP, tissue cyclic GMP levels reached a maximum at 1–3 min. The relaxation of tracheal smooth muscle began at 1 min and reached a maximum level at 5 min after the superfusion of BNP (10−6mol/L). The elevation of cyclic GMP preceded the relaxation of tracheal smooth muscle.5. These results suggest that BNP may have a potent relaxant effect on tracheal smooth muscle and this

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01676.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The effect of continuous intravenous administration of 1 UmUg/h atrial natriuretic peptide (ANP) for 4 days was studied in normal male Sprague‐Dawley rats and rats made nephrotic with puromycin aminonucleoside (PA).2. ANP infusion significantly increased urinary sodium and potassium excretion by 3 days of infusion in control rats but not in PA‐treated rats. ANP infusion significantly increased glomerular filtration rate in PA‐treated rats, while effective renal plasma flow was similarly decreased compared with non‐infused nephrotic rats.3. Plasma high density lipoproteins (HDL) were significantly decreased and low density lipoproteins (LDL) were increased in PA‐treated rats that received ANP; HDL were increased in normal rats infused with ANP.4. Competitive binding studies demonstrated a lower density of specific ANP receptors in glomerular membranes from rats injected with PA, while binding affinity was unchanged.5. Infusion with exogenous ANP did not promote natriuresis in PA nephrosis despite an enhancement of glomerular filtration rate (GFR), thus suggesting that sodium retention in this model is due to a post‐glomerular defect. Plasma lipoprotein composition in both normal and nephrotic rats may be affe

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01677.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The effects of the ACE inhibitor, captopril, on collagen metabolism in spontaneously hypertensive rats (SHR) with cardiac hypertrophy was examined. Captopril (100 mg/kg per day) was administered in drinking water to 20 week old male SHR for 12 weeks. Collagen concentration was calculated from hydroxyproline content, and relative proportions of types I, III and V collagen were determined by non‐interrupted SDS‐polyacrylamide gel electrophoresis (SDS‐PAGE). These parameters were examined in age and sex matched Wistar‐Kyoto (WKY) rats, as well as in non‐treated SHR, and compared with those of captopril‐treated SHR.2. Captopril significantly reduced both blood pressure (191 ± 12.1vs146 ± 11.2 mmHg,P<0.01), and the ratio of left ventricular (LV) weight to bodyweight (BW; 2.38 ± 0.17vs2.05 ± 0.12 mg/g,P<0.01). There were no significant differences in collagen concentration among WKY rats, captopril‐treated SHR and non‐treated 32 week old SHR. However, total collagen content in captopril‐treated SHR reduced significantly compared with non‐treated 32 week old SHR (16.8 ± 2.0vs21.3 ± 0.8 mg,P<0.01). The relative proportion of type V collagen was significantly higher in both captopril‐treated (58.6 ± 3.4vs46.8 ± 1.3%,P<0.01) and non‐treated 32 week old SHR (59.9 ± 3.1vs46.8 ± 1.3%,P<0.01) compared with WKY rats. However, there were no significant differences between captopril‐treated SHR and non‐treated 32 week old SHR.3. The data from this study showed that captopril reduced cardiac hypertrophy, as reported previously, but did not change collagen types and concentration o

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01678.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. Change with time of the content and uptake of dopamine (DA) and noradrenaline (NA) in the renal, superior mesenteric and femoral arteries and abdominal aorta of rabbit after reserpine administration was examined. Endogenous DA and NA were measured by high performance liquid chromatography coupled with electrochemical detector.2. A single dose of reserpine (3 mg/kg, i.p.) maximally depleted the endogenous DA and NA contents in the four blood vessels 24 h after the administration; the ratios of reductions were 70–90% and approximately 90% of the normal levels, respectively. The DA contents in all four vessels recovered to the normal level within 4 days after reserpine. However, NA content did not recover to the normal levels within 30 days after reserpine except in the mesenteric artery.3. The activity of dopamine β‐hydroxylase (DBH) significantly increased in all four blood vessels 1 h after reserpine. Although the DBH activity returned to the normal level after 3 days in the mesenteric artery, it returned within 24 h in the other three vessels.4. [3H]‐Dopamine and [3H]‐NA uptake were almost completely depressed 1 h after reserpine. The [3H]‐NA uptake in four vessels recovered to the normal level 2–14 days after reserpine, and [3H]‐DA uptake recovered after 30–45 days. Thus, the endogenous DA content in blood vessels was completely restored although DA uptake and NA content were still affected.5. These results suggested that the recovery of stored DA after reserpine was faster than that of stored NA and the recovery of DA uptake after reserpine was slower than NA uptake. This indicates a possibility that a part of DA pool may be different from NA pool in adrenergic nerve terminals in t

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01679.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. Albino Wistar rats were raised in a normobaric hypoxic environment (10% O2in N2). Two generations of hypoxic rats were observed for changes in their haemoglobin‐oxygen (Hb‐O2) dissociation curves (ODC), 2,3‐diphosphoglycerate (2,3‐DPG), haemoglobin (Hb), and Hill coefficients at P50(n50). The first generation were called (H1) and the second generation (H2). The control group (N) had a normoxic environment.2. Thirty‐five rats (13 N rats, 12 H1 rats and 10 H2 rats) were used. The 2,3‐DPG was significantly higher in both hypoxic groups when compared with N rats (2.02 ± 0.51 mmol/L) but 2,3‐DPG of H2 rats was significantly lower than that of H1 rats (H1 = 3.48±0.58 mmol/L and H2 = 2.76±0.54 mmol/L). The haemoglobin values were N = 2.00±0.26, H1 = 2.65±0.32and H2 = 2.36±0.30 mmol/L, respectively.3. We observed considerable differences in Hb‐O2affinity between the three groups of rats. In standard conditions (pH = 7.400; pCO2= 40 mmHg at 37°C) the H1 rats showed a significantly decreased Hb‐O2affinity (P50, st= 37.0 ± 1.3 mmHg) when compared with both H2 and N rats; the H2 rats showed a significantly increased Hb‐02 affinity (P50, st1 31.1 ± 1.5 mmHg) when compared with controls N (P50, st= 34.7±2.1 mmHg). There were no significant differences inn50values: N = 2.88 ± 0.44; H1 = 2.88 ± 0.77; and H2 = 2.94 ± 0.67.4. Therefore, the H1 rats’ ODC was located well to the right of that of N rats; and the H2 rats had an ODC located to the left when compared with both HI and N rats. It is likely that in H2 rats the adaptive processes to the new environment are more advanced; therefore, the magnitude of the compensatory mechanisms required to maintain a sufficient

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01680.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY