bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular and respiratory effects of cannabis in cat and rat
Authors: GRAHAM J. D. P. , LI D. M. F. 
Published: July 2012

Summary
In anaesthetized rats, intravenous administration of cannabis extract (10 mg/kg), Δ1‐tetrahydrocannabinol (THC) (0·5 mg/kg) and Δ6‐THC (0·5 mg/kg) caused a reduction in systemic blood pressure, pulse rate and respiratory rate.
Neither cannabinol (1 mg/kg, i.v.) nor cannabidiol (1 mg/kg, i.v.) had any observed effects on the cardiovascular and respiratory systems of the rat.
Pretreatment of rats with atropine (1 mg/kg, i.v.) reduced the hypotension and bradycardia caused by Δ1‐THC or the extract.
In anaesthetized cats with autoperfused hindquarters, cannabis extract (10 mg/kg, i.v.) and Δ1‐THC (0·2 mg/kg, i.v.) caused hypotension, bradycardia, depression of respiratory rate and reduction of hindlimb perfusion pressure.
Both cannabis extract and Δ1‐THC potentiated reflex vasodilatation and direct vasoconstriction in the hindlimb induced by intravenous noradrenaline in the cat; they reduced reflex hindlimb vasoconstriction elicited by histamine, acetylcholine or bilateral carotid occlusion.
Tolerance to these cardiovascular and respiratory effects of cannabis extract developed in rats which had been treated i.p. with the extract at (50 mg/kg) per day for 14 days.
Cardiovascular responses to injections of cholinomimetic drugs into the cerebral ventricles of unanaesthetized dogs
Authors: LANG W. J. , RUSH M. L. 
Published: July 2012

Summary
The cardiovascular and behavioural effects of cholinomimetic drugs injected through a cannula chronically implanted into a lateral cerebral ventricle were examined in unanaesthetized dogs.
Acetylcholine (ACh) (10–20 μg) produced an increase in arterial pressure and heart rate, the dogs became more alert, moved their heads, licked and swallowed and then became drowsy.
The responses to ACh were potentiated by intraventricular physostigmine (5 μg), were abolished by intraventricular atropine (100 μg) but were unaffected by intraventricular mecamylamine (250 μg). The responses to ACh were reproducible on any one day if injections were given again after a 30 min interval but tolerance developed when ACh was injected repeatedly over periods of several days.
Methacholine (40 μg) produced similar behavioural and cardiovascular effects to ACh but of a longer duration. The responses to methacholine were abolished by intraventricular atropine (100 μg).
Nicotine (20–60 μg) produced a biphasic cardiovascular response of an initial brief pressor response and tachycardia followed by a secondary increase in arterial pressure and heart rate which was greater in magnitude and duration. The secondary cardiovascular effects were associated with restlessness and vomiting.
The responses to nicotine were abolished by prior injection of mecamylamine (250 μg) but were unaffected by atropine (100 μg). The responses to nicotine were not reproducible if injections were repeated on the same day but could be again produced if a few days were allowed to elapse between injections.
An increased heart rate occurred during the pressor response to the cholinomimetic drugs but when a comparable pressor response was produced by intravenous infusion of noradrenaline in the same unanaesthetized dogs pronounced reflex bradycardia resulted.
The results indicate that the activation of both muscarinic and nicotinic cholinergic mechanisms leads to cardiovascular and behavioural effects in the conscious dog although the site of action and peripheral mechanisms have not been determined.
Selective blockade of β‐adrenoceptors by 1‐(p‐allylphenoxy)‐3‐isopropylamino‐2 propanol hydrochloride (H 64/52) in the anaesthetized dog
Authors: LEVY B. 
Published: July 2012

Summary
The β‐adrenoceptor blocking properties of l‐(p‐allylphenoxy)‐3‐isopropylamino‐2‐propanol hydrochloride (H 64/52) on the cardiovascular and broncho‐motor responses to isoprenaline have been determined in the anaesthetized dog.
H 64/52 selectively blocked the isoprenaline‐induced increase in heart rate, contractile force and reduction in airway pressure in the same dose range.
H 64/52 produced a minimal blockade of vascular β‐adrenoceptors which was apparent only when the isoprenaline‐induced fall in diastolic pressure was considered. No significant vascular β‐adrenoceptor blockade with H 64/52 could be shown with the femoral arterial flow or hind‐limb perfusion studies.
These results further support the hypothesis that several different β‐adrenoceptor subtypes exist in the dog. The β‐adrenoceptors subserving cardiac stimulation and bronchodilation appear to be similar and both differ from the β‐adrenoceptor subserving vasodilatation.
On the pharmacology of ascending, descending and recurrent postsynatic inhibition of the cuneo‐thalamic relay cells in the cat
Authors: KELLY J. S. , RENAUD L. P. 
Published: July 2012

Summary
In cats decerebrated or anaesthetized with pentobarbitone, cells of the middle third of the cuneate nucleus that were excited by tactile stimulation of the ipsilateral forelimb (responding to displacement of hairs, skin or joints) and inhibited by electrical stimulation of the contralateral pyramid, were invariably inhibited by electrical stimulation of the ipsilateral forepaw and the contralateral forelimb nerves.
In 50% of the cats, the cells were more fully identified by placing electrodes stereotaxically in the contralateral medial lemniscus. Recurrent inhibition was always a concomitant of the antidromic action potential.
The intensity and the duration of inhibition evoked by all of these pathways was totally resistant to iontophoretic and intravenous strychnine in doses at least 5 times that required to block completely the response of the same cells to iontophoretic glycine and was extremely sensitive to either iontophoretic bicuculline or picrotoxin.
Although the inhibition was invariably sensitive to intravenous picrotoxin, no significant change occurred in the duration or intensity of the inhibition when bicuculline was administered intravenously (5 or 6 times) as repeated doses of 0·2 mg/kg.
Postsynaptic inhibition in the cuneate may be mediated by γ‐aminobutyric acid released from the nerve terminals of a common pool of interneurones shared by ascending, descending and recurrent pathways. Since the receptors involved in this pathway are resistant to intravenous bicuculline, they may well be distinct from those responsible for changes in the primary afferent terminal excitability, usually believed to be associated with presynaptic inhibition.
Lithium kinetics in man: effect of variation in dosage pattern
Authors: BERGNER P‐E. E. , BERNIKER K. , COOPER T. B. , GRADIJAN J. R. , SIMPSON G. M. 
Published: July 2012

Summary
Utilizing a general stochastic theory of drug kinetics we have demonstrated that from the serum concentration curve derived from a single dose of lithium, it is possible to predict the steady state concentration, the time required to reach steady state, the dependency of these quantities on the time interval between drug administrations and the fluctuations in plasma level under steady state conditions.
It has been shown in general that the more frequently the drug is administered the higher is the steady state level, the shorter is the time required to reach steady state, and the smaller are the fluctuations.
EFFECTS ON PLASMA AND BRAIN TRYPTOPHAN IN THE RAT OF DRUGS AND HORMONES THAT INFLUENCE THE CONCENTRATION OF UNESTERIFIED FATTY ACID IN THE PLASMA
Authors: CURZON G. , KNOTT P.J. 
Published: July 2012

The effects on tryptophan distribution and metabolism of drugs altering plasma unesterified fatty acid (UFA) concentration were investigated in the rat.
UFA and plasma free (i.e. ultrafilterable) tryptophan altered in the same direction.
Catecholamines and l‐DOPA increased both plasma UFA and free tryptophan. l‐DOPA also increased brain tryptophan and 5‐hydroxyindoleacetic acid (5‐HIAA) but decreased brain 5‐hydroxytryptamine (5‐HT).
Aminophylline increased plasma UFA and free tryptophan and also brain tryptophan, 5‐HT and 5‐HIAA. Food deprivation had qualitatively similar effects.
Insulin decreased plasma UFA and free tryptophan in both fed and food‐deprived rats. However, while in fed rats these changes were associated with small decreases of brain indoles, in food‐deprived animals small increases occurred.
Nicotinic acid had only small effects in fed rats but it opposed both the UFA and indole changes in food‐deprived animals. Total plasma tryptophan increased in nicotinic acid treated, food‐deprived rats.
There was a tendency towards inverse relations between changes of plasma free and total tryptophan.
The results suggest that drugs which influence plasma UFA through actions on cyclic AMP thereby alter the binding of tryptophan to plasma protein and that this leads to altered distribution and metabolism of tryptophan.
RELEASE OF PROSTAGLANDINS FROM THE RABBIT PERFUSED KIDNEY: EFFECTS OF VASOCONSTRICTORS
Authors: GAGNON D.J. , GAUTHIER R. , REGOLI D. 
Published: July 2012

The rat stomach strip was used to assay prostaglandin E2‐like material released by a rabbit isolated kidney perfused with Krebs solution.
Doses of noradrenaline and angiotensin II producing similar vasoconstrictor effects released equivalent amounts of prostaglandins from the kidney.
8‐Leu‐angiotensin II, a specific inhibitor of the natural octapeptide, blocked the action of angiotensin II on perfusion pressure and the release of prostaglandins, while the action of noradrenaline on both parameters was unaffected.
Indomethacin, a specific inhibitor of prostaglandin biosynthesis, blocked the effects of both vasoconstrictors on prostaglandin release while their action on perfusion pressure was significantly enhanced.
In the kidney effluent, amounts of prostaglandin E2‐like material increased linearly with the rise in perfusion pressure induced by increasing doses of angiotensin II. These results indicate that prostaglandin output from the isolated kidney follows the rise in perfusion pressure.
INTERACTION OF CANNABIS AND GENERAL ANAESTHETIC AGENTS IN MICE
Authors: CHESHER G.B. , JACKSON D.M. , STARMER G.A. 
Published: July 2012

A cannabis extract (I) (in a concentration equivalent to 10 mg Δ9‐tetrahydrocannabinol(THC)/kg) prolonged pentobarbitone anaesthesia in mice maximally 20 min to 2 h after medication. The effect was still significant after 8 h, but less than at 2 hours.
The cannabis extract (I) (equivalent to 10 mg Δ9‐THC/kg) prolonged both pentobarbitone and ether anaesthesia in mice when administered 20 min before the anaesthetic. After eight consecutive daily doses of cannabis, the pentobarbitone anaesthesia was still significantly longer than a control group, while ether anaesthesia was not significantly prolonged.
A second cannabis extract (II) with a different ratio of cannabinoids (also administered in dosage equivalent to 10 mg Δ9‐THC/kg) failed to affect pentobarbitone anaesthesia in mice. This extract presented about 4% the dose of cannabidiol as extract I.
Δ8‐THC, Δ9‐THC and cannabidiol prolonged pentobarbitone anaesthesia with cannabidiol being generally more active than Δ9‐THC. Cannabinol (10 mg/kg) was inactive.
The effects of cannabidiol and Δ9‐THC were found to be additive, and there was a consistent trend for cannabinol to reduce the effectiveness of Δ9‐THC and cannabidiol when given in combination.
Premedication with phenoxybenzamine, phentolamine, propranolol, iproniazid, protriptyline, desipramine, reserpine, α‐methyl tyrosine or parachlorophenylalanine did not affect the extract I‐induced prolongation of pentobarbitone anaesthesia.
It is concluded that cannabis may affect pentobarbitone and ether anaesthesia in mice at least partially by a direct depressant effect, and that the cannabis‐induced prolongation of anaesthesia is probably unrelated to any effect on central 5‐hydroxytryptamine or catecholamine neurones.
DISTRIBUTION OF LOCAL ANAESTHETICS: ACCUMULATION IN SOME ENDOCRINE POLYPEPTIDE‐HORMONE PRODUCING CELL SYSTEMS
Authors: HAMMARSTRÖM L. , SLANINA P. , TJÄLVE H. , ULLBERG S. 
Published: July 2012

After the injection of labelled procaine and lidocaine in mice, the location and concentration of radioactivity was demonstrated by autoradiographical methods.
An accumulation in some endocrine cells such as the pancreatic islets, the hypophysis, the adrenal medulla and certain cells of the thyroid (probably representing the calcitonin‐producing parafollicular cells) was shown.
After the injection of [14C]‐procaine in chicks, an accumulation of radioactivity was observed in the ultimobranchial gland (which produces calcitonin in birds), but not in the thyroid.
Radioactivity was also shown to be strongly concentrated in structures containing melanin, such as the pigment of the eye, skin and hair and in some organs involved in the metabolism and excretion of these drugs.
ELECTROPHORESIS OF ISOLATED SECRETORY GRANULES FROM GUINEA‐PIG SUBMAXILLARY GLAND
Authors: BHOOLA K.D. , COGDELL R. 
Published: July 2012

The nature of the surface charge on secretory granules from the submaxillary gland of the guinea‐pig has been studied by electrophoresis of the isolated granules. The granules suspended in buffered sucrose solutions move to the anode.
Divalent ions reduce the anodal movements of the granules. Calcium and magnesium neutralize the net surface charge of the granules. This result supports the hypothesis that the electrostatic surface charge which can be reduced by calcium ions may be a major factor in controlling the fusion of secretory granules to the cell membrane, before release by exocytosis.
The mechanisms which couple membrane events with enzyme or hormone release from secretory glands are considered.
ACTIONS OF SOME ESTERS OF 3,3‐DIMETHYLBUTAN‐1‐OL (THE CARBON ANALOGUE OF CHOLINE) ON THE GUINEA‐PIG ILEUM
Authors: BARLOW R.B. , TUBBY JULIA H. 
Published: July 2012

Estimates were made of the affinity constants for postganglionic acetylcholine receptors of the guinea‐pig ileum of the esters of 3,3‐dimethylbutan‐1‐ol with benzilic, (±)‐cyclohexylphenylglycollic, (±)‐mandelic, and diphenylacetic acids.
Attempts were made to check the competitive nature of the antagonism by using as wide a range of concentrations of antagonist as possible, consistent with their limited solubility, and by testing some of the compunds in the presence of a known competitive antagonist.
By comparing the affinities with those of the corresponding quaternary nitrogen compounds, the contribution made by the positive charge in the onium group to the binding by receptors may be assessed and has been found to be variable. The carbon analogue of benziloylcholine has about one‐tenth of its affinity, that of (±)‐cyclohexylphenylglycolloylcholine has only about one‐sixtieth of its affinity, but that of (±)‐mandelylcholine has slightly higher affinity than that of (±)‐mandelylcholine itself.
3,3‐Dimethylbutylacetate appeared to be a partial agonist with an affinity constant of about 2.6 × 103. The contribution made by the positive charge to the binding of acetylcholine at these receptors therefore seems likely to lie within the range observed with antagonists and there is no reason to believe that there is necessarily greater intimacy of association by agonists than by antagonists.
Although the C—C and N—C bonds in —CMe3 and —NMe3 are similar in length, the groups do not occupy the same volume in solution in water.
MANGANESE IONS AND SYNAPTIC TRANSMISSION IN THE SUPERIOR CERVICAL GANGLION OF THE CAT
Authors: KOSTIAL KRISTA , LANDEKA M. , ŠLAT B. 
Published: July 2012

In the perfused superior cervical ganglion of the cat manganese ions (2.7 − 4.6 mm) caused a block of synaptic transmission and reduced the output of acetylcholine.
Calcium ions (8.4–10.5 mm) relieved the synaptic block produced by manganese and partially restored the acetylcholine output.
The presence of manganese also reduced the sensitivity of ganglion cells to injected acetylcholine.
Both effects of manganese were completely reversible.
INFLUENCE OF SKF‐525A CONGENERS, STROPHANTHIDIN AND TISSUE‐CULTURE MEDIA ON DESENSITIZATION IN FROG SKELETAL MUSCLE
Authors: TERRAR D.A. 
Published: July 2012

Microelectrodes have been used to follow changes in membrane potential at end‐plate regions of frog skeletal muscle fibres exposed to carbachol; the depolarizing drug was applied to narrow strips of muscle in a rapidly flowing solution containing relatively impermeant anions rather than chloride.
During prolonged applications of carbachol (10 to 20 μm), the depolarization caused by the drug showed a gradual decline which was attributed to desensitization.
Desensitization was little if at all affected by supplementing the external solution with factors present in tissue‐culture media, or by treating the muscle with strophanthidin (25 μm).
The rate of repolarization in the presence of carbachol (10 to 20 μm) was greatly increased by the SKF‐525A congeners pipenzolate bromide (10 μm) and adiphenine hydrochloride (1 μm). The desensitization‐enhancing action of these compounds is discussed.
EFFECT OF 6‐HYDROXYDOPAMINE ON [3H]‐ADENINE NUCLEOTIDE AND [3H]‐NORADRENALINE RELEASE FROM THE GUINEA‐PIG TAENIA CAECUM EVOKED BY ELECTRICAL FIELD STIMULATION, NICOTINE AND PERIVASCULAR NERVE STIMULATION
Authors: KUCHII M. , MIYAHARA J.T. , SHIBATA S. 
Published: July 2012

The effects of pretreatment of guinea‐pigs with 6‐hydroxydopamine (6‐OHDA) on the release of [3H]‐noradrenaline and [3H]‐adenine nucleotide following electrical field, nicotine and perivascular nerve stimulation of guinea‐pig taenia caecum were studied.
High frequency electrical field stimulation (15,30 Hz) released both [3H]‐noradrenaline and [3H]‐adenine nucleotide but low frequency (0.5, 5 Hz) stimulation, producing comparable muscle relaxation led only to [3H]‐noradrenaline release.
6‐OHDA (50–200 mg/kg) pretreatment inhibited the muscle relaxation and, [3H]‐noradrenaline release with electrical stimulation or with nicotine in isolated taenia but did not affect the release of [3H]‐nucleotide.
A low dose of 6‐OHDA (50 mg/kg), completely inhibited the muscle relaxation and [3H]‐noradrenaline release elicited by perivascular nerve stimulation.
Both tissue noradrenaline content and [3H]‐noradrenaline uptake were decreased to the same extent by low as well as high doses of 6‐OHDA: noradrenaline content was reduced to 20% and uptake to 30% of the control value.
Catecholamine fluorescence disappeared from tissue layers of the taenia after treatment with a high dose of 6‐OHDA.
In these experiments the inhibitory action of electrical stimulation and nicotine on the taenia can be correlated better with noradrenaline than with nucleotide release.
THE EFFECTS OF INDOMETHACIN AND EICOSA‐5,8,11,14‐TETRAYNOIC ACID ON THE RESPONSE OF THE RABBIT PORTAL VEIN TO ELECTRICAL STIMULATION
Authors: GREENBERG R. 
Published: July 2012

The effects of indomethacin and eicosa‐5,8,11,14‐tetraynoic acid (ETYA) on the contractile response of the transmurally stimulated rabbit portal vein were studied in vitro.
When the veins were stimulated for 240 pulses at 1 and 2 Hz, the responses were potentiated by indomethacin and ETYA. However, responses to 4 and 8 Hz were not potentiated. The responses to continuous electrical stimulation at 2 Hz were also potentiated by indomethacin and ETYA. This potentiating effect was attenuated when the veins were pretreated with α‐methyl‐p‐tyrosine. The responses of the veins to noradrenaline were not altered by either indomethacin or ETYA.
Prostaglandin E2 inhibited the responses of the portal vein to electrical stimulation. The magnitude of this inhibition was inversely related to the frequency of stimulation. The responses of the vein to noradrenaline were not altered by prostaglandin E2.
It is concluded that potentiation by indomethacin and ETYA of the response of the isolated portal vein is due to an increased release of newly synthesized noradrenaline as a result of inhibition of prostaglandin synthesis.
EFFECTS OF FASTING, STRESS AND DRUGS ON GASTRIC GLYCOPROTEIN SYNTHESIS IN THE RAT
Authors: DEKANSKI J.B. , MACDONALD A. , SACRA P. , PARKE D.V. 
Published: July 2012

The relationship between gastric mucosal damage and synthesis of gastric glycoproteins, as measured by the rate of incorporation of N‐acetyl‐[3H]glucosamine, was investigated in rats after fasting and restraint stress and a single administration of aspirin (200 mg/kg, orally), phenylbutazone (200 mg/kg, orally), prednisolone (200 mg/kg, orally), or adrenaline (2 mg/kg, i.p.). In one experiment, the effects of aspirin and phenylbutazone on carbohydrate content of the glycoproteins were also determined.
Restraint stress, phenylbutazone and aspirin resulted in acute gastric mucosal erosions in some of the rats. Adrenaline produced severe sub‐mucosal haemorrhage, but no erosions or ulceration, while prednisolone and fasting gave no gross pathology.
The rate of incorporation of N‐acetyl‐[3H]glucosamine into glycoproteins was decreased after all treatments except adrenaline. In the groups receiving restraint stress, aspirin or phenylbutazone, the decreases were more marked in rats which developed erosions than in those with no gastric pathology.
Aspirin and phenylbutazone also produced changes in the carbohydrate content of the glycoproteins, the effects again being greater in the rats which developed erosions.
The results are discussed in the context of a possible association between erosion formation and glycoprotein synthesis and it is proposed that inhibition of mucus glycoprotein biosynthesis may be one mode of action of stress and drugs in causing gastric mucosal damage.
RESPONSE OF RAT LUNG TO HUMORAL MEDIATORS OF ANAPHYLAXIS AND ITS MODIFICATION BY DRUGS AND SENSITIZATION
Authors: CHURCH M.K. 
Published: July 2012

The effects of humoral mediators of anaphylaxis on the bronchial function of the pithed rat have been assessed and compared with their effects in the guinea‐pig and man.
5‐Hydroxtryptamine, acetylcholine and bradykinin were bronchoconstrictor. Slow reacting substance in anaphylaxis and prostaglandin F2α caused only slight constriction at high doses and histamine was not active.
Bradykinin was less active in the rat than in the guinea‐pig and its effects were not antagonized by anti‐inflammatory analgesic drugs.
β‐Adrenoceptor blockade potentiated the activity of bradykinin but not that of 5‐hydroxytryptamine or acetylcholine.
Dexamethasone reduced the activity of bradykinin but not that of 5‐hydroxytryptamine or acetylcholine.
Sensitization with Nippostrongylus brasiliensis did not increase the sensitivity of the rat lung to the effects of mediators.
ADENOSINE AND DIPYRIDAMOLE ACTIONS AND INTERACTIONS ON ISOLATED CORONARY ARTERY STRIPS OF CATTLE
Authors: KALSNER S. 
Published: July 2012

The actions and interactions of adenosine and dipyridamole were investigated on isolated strips of coronary arteries of beef cattle. It was found that small diameter arteries (about 0.5‐1.0 mm o.d.), raised to a moderate level of tone with potassium, responded with relaxation to low concentrations of adenosine.
Dipyridamole, over a broad concentration range (6.0 × 10−8‐2.0 × 10−5 M), enhanced these responses, shifting the adenosine concentration‐response curve (3.7 × 10−8‐1.1 × 10−4 M) considerably to the left. In contrast, inhibitory concentration‐response curves to sodium nitrite and to noradrenaline were not materially altered by dipyridamole.
Studies of the uptake of [3H] ‐adenosine revealed a rapid uptake of the nucleoside by coronary artery strips, which was inhibited by dipyridamole (6.0 × 10−8‐2.0 × 10−5 M); but this may not be sufficient to account fully for the observed sensitization.
It is concluded that the regulation of adenosine responses and the action of dipyridamole in the heart involve a more direct association with coronary vascular tissue than has been previously appreciated.