摘要:

SUMMARY1. The effects of optical isomers of nicardipine on the secretion of pancreatic juice and blood flow were investigated in the dog‐isolated, blood‐perfused pancreas.2. Intra‐arterial administration of (‐)‐nicardipine (10–300 μg) caused a dosedependent increase in pancreatic secretion. However, the (+)‐isomer was much less potent than the (‐)‐isomer and even in 300 μg of (+)‐isomer caused only a slight secretion.3. (+)‐ And (‐)‐nicardipine increased perfusion blood flow in a dose‐dependent manner, and (+)‐nicardipine was approximately five times as potent as the (‐)‐isomers. The maximum increase in a flow rate was produced by 30 μg of (+)‐isomer and 100 μg of (‐)‐isomer.4. Bicarbonate concentration in pancreatic juice induced by (‐)‐ and (+)‐nicardipine was increased in a dose‐dependent manner, but the protein concentration was only increased slightly.5. From these results, it is concluded that there is a stereoselectivity in the secretory and

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1984.tb00233.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARY1. The haemodynamic effects and pharmacokinetics of a single orally administered dose of 0.5 mg of prazosin have been compared in six patients with stable severe congestive cardiac failure. Administration of prazosin induced significant decreases in mean pulmonary capillary wedge pressure (from 27.5, s.e.m.=4.5 to 19.4, s.e.m.=5.1 mmHg;P<0.001), mean arterial blood pressure (from 94.5, s.e.m.=6.0 to 85.4, s.e.m.=5.0 mmHg;P<0.01), and systemic vascular resistance (from 1690, s.e.m.=360 to 1420, s.e.m.=200 dyn. s/cm5;P<0.05) and a rise in cardiac index from 1.98 (s.e.m.=0.07) to 2.28 (s.e.m.=0.16) litres/min per m2(P<0.05). There was a non‐significant fall in heart rate.2. Pharmacokinetic analysis revealed maximum plasma prazosin concentrations of 4.1 (s.e.m.=1.4) ng/ml, occurring 2.1 (s.e.m.=0.4) h after drug ingestion. The mean elimination half‐life was 5.1 (s.e.m.=0.8) h, which is longer than that found in our previous studies in normal subjects. There was considerable interindividual variation in peak plasma prazosin concentrations, elimination half‐life and area under the concentration‐time curve. While mean maximal haemodynamic effects of prazosin occurred at similar times to the peak plasma concentration of the drug, there was no significant correlation between the extent of haemodynamic response and individual pharmacokinetic parameters.3. It is concluded that significant and potentially beneficial haemodynamic effects occur with the initial administration of 0.5 mg oral doses of prazosin in patients with stable congestive cardiac failure and it is suggested that in many patients little advantage will be achieved with higher initia

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1984.tb00234.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARY1. The removal of hyaluronic acid (HA) from the blood‐stream was studied in four normal human subjects after injection of high molecular weight preparations labelled with3H in the acetyl position. The plasma half‐life of the injected material ranged between 2.5 and 5.5 min.2. The daily turnover of HA in the circulation was estimated to be at least 150 mg. Its elimination was predominantly extrarenal, the upper molecular weight limit for renal excretion being 25 000.3. Evidence for rapid degradation was provided by the identification of3H2O in urine. Calculations from the specific activity of urinary3H2O indicated that approximately 55% of the acetyl content of the injected HA was completely oxidized within 3 h, and 85% within the first day.4. It is concluded that hyaluronic acid in the amounts currently used for therapeutic purposes should not accumulate significantly in the circulat

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1984.tb00235.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARY1. The antagonist effects of indoramin were investigated in rabbit perfused ear artery, common carotid artery, and human perfused temporal artery preparations.2. Indoramin was a potent competitive antagonist of the constrictor effects of noradrenaline (NA) in all three preparations, pA2values being 7.77 for the ear artery, 8.20 for the common carotid artery and 7.46 for the human temporal artery.3. The constrictor actions of serotonin (5‐hydroxytryptamine, 5‐HT) were competitively antagonized by indoramin. The pA2values obtained in the rabbit common carotid and human temporal artery (5.92 and 6.25, respectively), were lower than those for NA in the same preparations and lower than that obtained in the rabbit perfused ear artery (7.55).4. Indoramin was a potent competitive antagonist (pA2:8.31) of histamine‐induced vasoconstriction in the rabbit perfused ear artery preparation.5. These results can be explained on the basis of previous findings that the action of 5‐HT in the rabbit ear artery is mediated via an α‐adrenoceptor, and that the rabbit common carotid artery contains true 5‐HT receptors. The findings suggest that specific 5‐HT receptors may be present in the human temporal artery and that α‐adrenoceptor antagonism may be the pharmacological property of most relevance to the efficacy of indoramin in mig

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1984.tb00236.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARY1. Normotensive (WKY) and stroke prone spontaneously hypertensive (SHR‐SP) rats were given methyldopa (200 mg/kg i.p.) daily for five days and their brains were then sectioned and processed with the Faglu method for catecholamine fluorescence.2. This treatment with methyldopa induced a green fluorescence not seen in control animals, in cells coinciding with the B1–B9 groups of serotonin neurons in the brainstem.3. Pretreatment with the neurotoxin 5,7‐dihydroxytryptamine (5,7‐DHT, i.c.v.), which is relatively specific for serotonin neurons, prevented the appearance of this green fluorescence in the serotonin cell groups of rats given methyldopa.4. Pretreatment with 5,7‐DHT, i.c.v. approximately halved the magnitude of the hypotensive response to a single dose of methyldopa (80 mg/kg i.p.).5. We suggest that central serotonin nerves contribute to the hypotensive action of methyldopa.6. It is our hypothesis that methyldopa is taken up by these serotonin cells and that the green fluorescence reflects the production of α‐methyldopamine, as a result of decarboxylation by the ubiquitous enzyme, L‐aromatic amino acid

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1984.tb00237.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARY1. Although gastrin is found in adult gastric juice, rapid enzymatic destruction by pepsin in the acid environment makes a physiological role in the adult unlikely.2. Gastric pH in the fetal sheep is neutral so that gastric juice gastrin could be present, and if present, have a physiological function.3. The aim of this study was to determine the presence, molecular forms and metabolism of gastrin in gastric juice.4. Gastrin was present in fetal gastric juice at significantly higher concentrations than in fetal plasma.5. The majority of gastric juice gastrin was present as the biologically active gastrin‐17.6. Gastrin was stable in normal fetal gastric juice, but was rapidly metabolized to smaller C‐terminal fragments when the gastric juice was acidified.7. With the known growth promoting effect of gastrin on gastrointestinal mucosa, gastrin in fetal juice could have a unique role in thein uterodevelopment of the gastrointestinal tr

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1984.tb00238.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARY1. Changes induced by adrenalectomy, triamcinolone treatment and deoxycorticosterone (DOC) treatment on the uptake of [3H]‐serotonin into platelets were studiedex vivo, using rat platelets suspended in physiological medium.2. Adrenalectomy caused a decrease in active uptake of serotonin and an associated increase in apparentKm.3. Treatment of the adrenalectomized rats with triamcinolone (0.25 mg/kg), but not DOC (1.0 mg/kg) restored the active uptake of serotonin.4. At triamcinolone dose of 0.5 mg/kg, the serotonin uptake was raised to a level that was significantly higher than normal.5. Kinetic analysis of uptake data showed the apparentKm, to be affected by both triamcinolone and DOC, while the apparent Vmaxof uptake rate was increased by triamcinolone treatmen

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1984.tb00239.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARY1. The effects of histamine and histamine antagonists on bile flow have been studied using the cholecystectomized conscious sheep. Histamine stimulated bile flow in a dose‐dependent manner (D50= 15.7 μg/h per kg). Free water and HCO3−output were increased after intravenous histamine infusion. With histamine at 120 mg/h per kg, there was a 41.0 (s.d. = 4.6)% and 38.7 (s.d. = 4.2)% (n= 6) increase in bile volume and HCO3−output respectively. Bile salt concentration was decreased after intravenous histamine, but net bile salt secretory rate remained unchanged. There was no change observed in the molar ratios of bile salts:phospholipids:cholesterol. Total lipids were decreased from 2.2 (s.d. = 0.3) to 1.60 (s.d. = 0.4) g/dl (n=6). The corrected lithogenic index did not change significantly.14C‐Erythritol clearance also increased during histamine infusion in a dose‐dependent manner but did not correspond to increments in bile flow.2. The histamine H1‐receptor antagonist, diphenhydramine 0.05–1.0 mg/h per kg did not alter histamine stimulated bile flow. The H2‐receptor antagonists, cimetidine (0.5–4 mg/h per kg) and ranitidine (0.05–0.5 mg/h per kg) progressively reversed the histamine‐induced choleresis. Maximum inhibitory effect was attained at 2.0 and 0.25 mg/h per kg for cimetidine and ranitidine, respectively. At these levels, variation of intravenous infusion of histamine did not result in competitive displacement of the inhibitory response by either cimetidine or ranitidine. Moreover, concomitant infusion of diphenhydramine at 1.0 mg/h per kg potentiated the inhibitory effect of cimetidine or ranitidine on histamine‐induced choleresis.3. Histamine increases the bile salt independent component of hepatic bile flow. This increase can be blocked by cimetidine or ranitidine by a non‐compet

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1984.tb00240.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARY1. The responses to 20% haemorrhage were examined in conscious rabbits with or without inhibition of prostaglandin production by indomethacin (5 mg/kg +0.5 mg/kg per h i.v.). In rabbits not pretreated with indomethacin, haemorrhage lowered mean arterial pressure by 6.3 (s.e.m. = 1.6) mmHg, renal blood flow by 22.8 (s.e.m. = 3.4) ml/min and glomerular filtration rate (GFR) by 3.4 (s.e.m. = 0.6) ml/min, and raised plasma renin activity by 5.2 (s.e.m. = 1.0) ng/ml per h. Pretreatment of the rabbits with indomethacin did not significantly alter the responses to haemorrhage. Mean arterial pressure fell by 10.9 (s.e.m. = 1.8) mmHg, renal blood flow by 24.9 (s.e.m. = 3.9) ml/min and GFR by 4.2 (s.e.m. = 1.8) ml/min and plasma renin activity rose by 3.2 (s.e.m. = 0.5) ng/ml per h.2. In a separate group of 5 rabbits, angiotensin II was infused at 10, 25 and 50 ng/kg per min i.v. or methoxamine was infused at 10 and 25 μg/kg per min i.v. After indomethacin pretreatment, angiotensin II caused a significantly greater rise in mean arterial pressure and greater fall in renal vascular conductance, but there was no effect on the GFR response. In contrast, methoxamine caused significantly smaller falls in GFR, renal blood flow and renal vascular conductance after indomethacin pretreatment.3. Indomethacin significantly lowered resting GFR but not renal blood flow or arterial pressure.4. Thus, indomethacin pretreatment accentuated the renal vasoconstriction to angiotensin II, reduced the renal vasoconstriction to methoxamine and had no effect on the responses to haemorrhage.5. The results therefore suggest that prostaglandins do not act to lessen the renal effects of all vasoconstrictor stimuli, but that the prostaglandin response depends on the nature of the ischaemic stimulus

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1984.tb00241.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARY1. Adrenaline 1 μg markedly elevated the activity of adenylate cyclase in ventricular tissue of rat hearts.2. Δ1‐THC 25, 50 and 100 μg significantly reduced the adenylate cyclase activity with the maximum effect observed with the dose or 25 μg. Doses below or above this range did not produce any significant effect on the enzyme activity.3. Neither Δ6‐THC 25 and 100 μg nor PVP 400 μg had any significant action on adenylate cyclase.4. The Δ1‐THC‐induced lowering of the cyclic AMP concentration in ventricular tissue of rat hearts can be explained, at least partly, by its ability to reduce the activity of adenylate cyclase in these tissues. It is suggested that this enzyme inhibition underlies the cardiac depressant a

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1984.tb00242.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY