bluuebunny/crossref_metadata_2025_split huggingface dataset:
Etomidate‐anaesthesia, with and without fentanyl, compared with urethane‐anaesthesia in the rat
Authors: De Wildt D.J. , Hillen F.C. , Rauws A.G. , Sangster B. 
Published: July 2012

In spontaneously breathing rats, continuous infusion of etomidate with and without fentanyl caused a slight decrease in blood pressure and heart rate. Coadministration of fentanyl and etomidate in order to obtain full anaesthesia and analgesia resulted in respiratory depression.
In artificially ventilated rats both etomidate as well as the anaesthetic combination caused a strong reduction in aortic flow and an increase in total peripheral resistance. A single infusion of etomidate did not change blood pressure. Etomidate combined with fentanyl reduced blood pressure. Under adjusted ventilation blood pressure, aortic flow, max(dF/dt) and heart rate were progressively reduced during a 4 h period.
In contrast, urethane anaesthesia reduced aortic flow to a minor extent. Total peripheral resistance and max(dF/dt) were hardly affected. The slightly reduced blood pressure and blood gas variables remained stable during the experiment.
From pharmacokinetic studies it was established that effective etomidate plasma levels were maintained constant during the experimental period. Pharmacokinetic interaction between etomidate and fentanyl did not occur.
It is concluded that for anaesthesia of longer duration during cardiovascular experiments in rats, urethane is preferable to etomidate/fentanyl because it does not cause serious changes in basal haemodynamic variables.
Cardiovascular responses in rats with glycerol‐induced acute renal failure
Authors: Bowmer C.J. , Nichols A.J. , Warren Maxine , Yates M.S. 
Published: July 2012

Autonomic and cardiovascular function were assessed in rats with glycerol‐induced acute renal failure (ARF).
Rats with ARF had significantly lower mean arterial blood pressures and heart rates and significantly elevated plasma noradrenaline concentrations.
The chronotropic responses to right cervical sympathetic and vagal stimulation were diminished in rats with ARF.
The pressor and depressor responses to noradrenaline and nitroprusside respectively when expressed as a change in mmHg pressure were significantly reduced in rats with ARF when compared to controls. However, when the depressor responses to nitroprusside were expressed as a percentage fall in basal mean arterial pressure, with the exception of the response to a dose of 10 μg kg−1, there were no significant differences between control and uraemic rats.
The present findings show that in the rat, changes in cardiovascular responsiveness occur after a brief period of uraemia which are similar to those observed in patients and rats with chronic renal failure.
Metabolism and uptake of adenosine in rat isolated lung and its inhibition
Authors: Bakhle Y.S. , Chelliah R. 
Published: July 2012

The metabolism of adenosine perfused through the pulmonary circulation of isolated lungs from rats was investigated radiochemically.
Following a 10 s infusion of radioactive [14C]‐ or [3H]‐adenosine, the recovery of radioactivity in effluent from the lung after 1 min increased from 30% at 0.5 μm to 80% at 1 mm adenosine.
Unchanged adenosine comprised the major radioactive species in effluent, being about a third of the total up to 100 μm.
Uptake of radioactivity was saturable at high concentrations with an apparent Km of 215 μm.
Radioactivity retained in lung comprised over 80% as ATP and about 2% as adenosine at all concentrations.
Perfusion of lungs with Krebs solution containing dipyridamole (1–100 μm) or adenine (10 μm) increased the rate of radioactive efflux, decreased uptake of radioactivity by lung and decreased metabolites of adenosine (inosine and hypoxanthine) in the effluent.
Dipyridamole (10 UM) was more potent in decreasing uptake in guinea‐pig lungs than in rat lungs.
From these results we conclude that the pulmonary circulation in rat lung exhibits a significant inactivation process for adenosine. The isolated lung provides a convenient preparation for studying in situ pharmacological or pathological modifications of this vascular inactivation process.
Phenolphthalein stimulates the formation of histamine, 5‐hydroxytryptamine and prostaglandin‐like material by rat jejunum, ileum and colon
Authors: Autore G. , Capasso F. , Mascolo N. 
Published: July 2012

The effects of Phenolphthalein on the formation of histamine, 5‐hydroxytryptamine (5‐HT) and prostaglandin‐like material by rat intestine were examined in vivo.
Phenolphthalein, in a dose that causes laxation increased the formation of histamine, 5‐HT and prostaglandin‐like material, and indomethacin reduced these increases.
The data support the idea that the laxative effect of Phenolphthalein is due to increased intestinal production of prostaglandin, histamine and 5‐HT.
Effects of noradrenaline and acetylcholine on electro‐mechanical properties of the guinea‐pig portal vein
Authors: Nanjo Tamaki 
Published: July 2012

Effects of acetylcholine (ACh) and noradrenaline (NA) on mechanical properties of smooth muscle cells of the guinea‐pig portal vein were investigated using intact and skinned muscle preparations. In some preparations, the electrical activity was also recorded. In addition to ACh and NA, the effects of caffeine, procaine, excess concentrations of [K]o and MnCl2 were investigated.
NA enhanced the mechanical response due to increase in the spike generation, receptor activated depolarization and release of Ca stored in the cell.
ACh also enhanced the mechanical response, but this agent had little effect on the Ca release from the storage sites.
Caffeine and procaine (10 mm) depolarized the membrane and enhanced the electrical activity. Caffeine enhanced the mechanical activity due to an increase in the membrane activity and the release of Ca stored in the cell, while procaine inhibited the contraction. Procaine inhibited and caffeine accelerated the Ca‐induced Ca‐release mechanism in the cell. NA released the Ca from the storage sites to a greater extent than did caffeine or ACh.
MnCl2 inhibited the spontaneous membrane activity and contraction; however, low concentrations of MnCl2 increased the caffeine‐ or NA‐induced contraction in Ca‐free solution.
When the Ca‐tension relationship was observed in saponin‐treated skinned muscles, the minimum concentration of Ca required to produce the contraction was 10−7 m, as observed in other vascular tissues. Caffeine released the stored Ca, NA and ACh had no effect on the Ca release and procaine inhibited the caffeine‐induced Ca release in skinned muscles.
It was concluded that the membrane properties of smooth muscle cells in the portal vein are much the same as observed in other spontaneously active visceral muscles. Differences observed in the actions of NA and ACh on mechanical properties seems to be mainly due to different receptor‐operated Ca release mechanisms.
Strontium, nifedipine and 4‐aminopyridine modify the time course of the action potential in cells from rat ventricular muscle
Authors: Mitchell Mary R. , Powell T. , Terrar D. A. , Twist V.W. 
Published: July 2012

Action potentials, initiated by brief depolarizing pulses, were recorded from single cells isolated from rat ventricular muscle. These action potentials showed a rapid upstroke to about + 30 mV, followed by two phases of repolarization referred to as the early and late phases of the action potential.
Nifedipine (1 μm), which blocks the second inward current (Isi) carried by Ca in these cells, shortened the early phase.
Substitution of strontium for calcium in the solution bathing the cells, a procedure which prolongs Isi, prolonged the early phase.
4‐Aminopyridine (1 mm), which inhibits transient outward current, prolonged the early phase with either calcium or strontium in the external solution.
It is concluded that both Isi and transient outward current contribute to the early phase of the action potential in rat ventricular muscle. It is also suggested that Isi does not directly contribute to the late phase, since the characteristics of the late phase are not compatible with such a role, and the possibility of additional inward current is investigated in the accompanying paper (Mitchell et al., 1984).
Indirect evidence that purinergic modulation of perivascular adrenergic neurotransmission in the portal vein is a physiological process
Authors: Burnstock Geoffrey , Crowe Rahima , Kennedy Charles , Török Josef 
Published: July 2012

The effects of adenine nucleotides and nucleosides on the contractile response to perivascular nerve stimulation were compared in the isolated portal vein of rabbit, rat and guinea‐pig.
2‐Chloroadenosine was more potent than adenosine and ATP, which were equipotent in producing inhibition of neurogenic contractions in the rabbit and rat via prejunctional P1‐purinoceptors.
In contrast, neurogenic contractions of the guinea‐pig portal vein were not inhibited by adenosine and were potentiated by 2‐chloroadenosine and, to a lesser extent, by ATP.
Fluorescence histochemical localization of quinacrine, which binds to high levels of ATP, revealed a dense perivascular nerve plexus in the portal vein of rabbit and rat but not of guinea‐pig.
After chemical sympathectomy, quinacrine‐positive nerves persisted in the rabbit (supporting other evidence for the presence of purinergic nerves) but not in the rat (supporting other evidence for ATP as a cotransmitter in adrenergic nerves).
It is concluded that a prejunctional purinergic modulatory mechanism operates in adrenergic neurotransmission in the portal vein of rabbit and rat but not guinea‐pig, and it is suggested that this indicates a physiological mechanism.
Substituted benzaldehydes designed to increase the oxygen affinity of human haemoglobin and inhibit the sickling of sickle erythrocytes
Authors: Beddell C.R. , Goodford P.J. , Kneen G. , White R.D. , Wilkinson S. , Wootton R. 
Published: July 2012

Substituted benzaldehydes have been designed to bind preferentially to the oxy conformation of human haemoglobin at a site between the amino terminal residues of the α‐subunits. Such compounds should stabilize the oxygenated form of haemoglobin and thereby increase its oxygen affinity.
The compounds produce the expected effect, left‐shifting the oxygen saturation curve of dilute haemoglobin solutions and of whole blood, although the binding pattern to haemoglobin is more complex than envisaged by the design hypothesis.
The predicted best compound is also a potent inhibitor, at low oxygen pressure, of the sickling of erythrocytes from patients homozygous for sickle cell disease, and may prove to be a clinically useful anti‐sickling agent.
Selective antinociceptive effects of tizanidine (DS 103–282), a centrally acting muscle relaxant, on dorsal horn neurones in the feline spinal cord
Authors: Davies J. , Johnston S.E. 
Published: July 2012

The effects of the centrally acting muscle relaxant tizanidine (DS103–282) have been examined on the responses of laminae IV and V dorsal horn neurones to peripheral noxious and non‐noxious stimuli in cats spinalized at L1.
Iontophoretic ejection of tizanidine near the cell bodies of the recorded neurones or more dorsally into laminae II‐III resulted in a marked and prolonged depression of excitation of laminae IV and V neurones evoked by noxious stimuli. Spontaneous firing was also depressed in many neurones but responses to innocuous stimuli were unaffected.
Intravenous administration of tizanidine also produced a long lasting and selective reduction in responses of laminae IV and V neurones to noxious stimuli and depressed the long latency excitation of these neurones evoked by electrical stimulation of small diameter unmyelinated primary afferents.
In contrast to the selective antinociceptive effect of tizanidine, ejection of γ‐aminobutyric acid (GABA) near laminae IV and V neurones or isoguvacine into laminae II‐III produced parallel reductions in responses to noxious and non‐noxious stimuli. Furthermore, ejections of the excitant amino acid kainate into laminae II‐III produced parallel enhancement of responses induced by both types of stimuli.
The site and mechanism of the antinociceptive action of tizanidine is not known but does not appear to involve an interaction with opiate receptors as it was not antagonized by naloxone. The possibility is discussed that tizanidine acts at synapses formed between excitatory interneurones in lamina II or III and laminae IV and V neurones, either interfering with transmitter release or its postsynaptic action.
The effects of iontophoretically administered tizanidine are quite distinct from those of baclofen, which produced non‐selective depression of responses to both noxious and innocuous stimuli, but were similar to those of noradrenaline. This raises the possibility that noradrenaline and tizanidine may act at a common site in the spinal cord.
Effect of muscarinic ligands on the electrical activity recorded from the hippocampus: a quantitative approach
Authors: Bevan Paul 
Published: July 2012

The electrical activity of the hippocampus was recorded from the CA 1 region in rats anaesthetized with halothane and the effects of compounds assessed following their intravenous injection. Quantification of the effects was achieved following on‐line fast Fourier transformation of the signal.
The electrical activity recorded from the hippocampus of the halothane‐anaesthetized rat demonstrated identical characteristics to that recorded from the freely‐moving animal.
Three types of activity could be distinguished: rhythmical slow wave activity (RSA or theta); large amplitude slow wave activity (LIA); and small amplitude fast wave activity.
Muscarinic agonists induced RSA with a consequent reduction in power. The effects were dose‐dependent and were reversibly antagonized by scopolamine, but not methyl‐scopolamine, indicating that the effects are mediated centrally by muscarinic receptors.
The results show that, in halothane anaesthetized rats, a muscarinic RSA occurs which is unrelated to movement or behavioural arousal.
Effects of α2‐adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets
Authors: Clare Katherine A. , Scrutton Michael C. , Thompson Neil T. 
Published: July 2012

A range of 2–(,5‐dihydroimidazolyl)‐benzene, ‐quinoline, and ‐quinoxaline derivatives and 2‐morpholino‐4‐catechol have been characterized as agonists or partial agonists for human platelet aggregation; and for inhibition of adenylate cyclase by measurement of their effect on platelet [cyclic‐3′,5′‐AMP]. Antagonist activity for these compounds versus adrenaline as agonist has also been assessed for these two responses.
The compounds can be divided into 4 groups. Group I contains compounds that are agonists for both responses; group II, compounds that are agonists for inhibition of adenylate cyclase but antagonists for the aggregatory response; group III, compounds that are agonists for the aggregatory response but are antagonists for inhibition of adenylate cyclase by adrenaline; and group IV, compounds that are antagonists for both responses.
In group I the EC50 values for induction of aggregation are not significantly different from the EC50 values for inhibition of adenylate cyclase except for 2‐morpholino‐4‐catechol which is significantly more potent as an inhibitor of adenylate cyclase.
In group IV a linear correlation is observed between the K1 values for the two responses for 8 compounds but 2 other compounds do not conform to this correlation.
The data are not consistent with a model in which a single x2‐adrenoceptor mediates both the aggregatory response and inhibition of adenylate cyclase and hence support a model in which unique x2‐adrenoceptors mediate these two responses.
The inhibitory effect of aspirin on lymphatic contractility
Authors: Allen J.M. , Burke E.P. , Johnston M.G. , McHale N.G. 
Published: July 2012

Spontaneous contractions and those elicited by two different methods of electrical stimulation were studied in isolated segments of bovine mesenteric lymphatic vessels.
The effect of aspirin (a cyclo‐oxygenase inhibitor) on spontaneous and evoked contractions of isolated lymphatic vessels was investigated.
Aspirin at doses of 10−6m or greater depressed both spontaneous and action potential‐dependent evoked contractions, but failed to inhibit contractions evoked by high current field stimulation. These latter contractions were rapidly depressed by the application of D600.
When aspirin was applied for five minute periods, inhibition never occurred within the period of drug administration but was delayed, with maximum inhibition occurring approximately 10 min after washout of the drug.
It is concluded that the inhibitory action of aspirin is unlikely to be a non‐specific depression of the contractile mechanism, but rather a reduction in excitability probably as a result of cyclo‐oxygenase inhibition.
Glutamate inhibitory action of matrine at the crayfish neuromuscular junction
Authors: Ishida M. , Shinozaki H. 
Published: July 2012

The effect of some alkaloids from Sophora flavescens (matrine, oxymatrine and N‐methylcytisine) on glutamate‐induced responses was investigated using electrophysiological techniques at the crayfish neuromuscular junction.
At concentrations greater than 0.1 mm, matrine depressed both glutamate‐induced responses and neurally evoked excitatory junctional potentials. Oxymatrine was less powerful than matrine, and N‐methylcytisine was not effective. Matrine also depressed quisqualate‐induced responses at this site, but did not have an effect on γ‐aminobutyric acid (GABA)‐induced responses. Matrine had no influence upon either the resting membrane potential or the input resistance of the crayfish opener muscle.
The inhibition of the glutamate‐induced response by matrine was not affected by the membrane potential of the muscle fibre.
Matrine reduced the size of extracellularly recorded excitatory junctional potentials without affecting their quantal content.
Matrine did not affect the decay of extracellular excitatory junctional currents at the resting membrane potential.
The results presented clearly demonstrate that matrine has an inhibitory action on glutamate‐induced responses.
Effects of dopamine and bromocriptine on colonic motility in dog
Authors: Bueno L. , Fargeas M.J. , Fioramonti J. , Honde C. 
Published: July 2012

The effects of intravenous infusions of dopamine (0.1 to 1 mg kg−1 h−1) and bromocriptine (10 to 40 μg kg−1 h−1) on colonic motility were investigated in fasted dogs fitted with permanent strain gauges on the ascending, transverse and descending colon.
Infused at rates of 0.5 and 1 mg kg−1 h−1 during 1 h, dopamine immediately stimulated the motility of the descending colon; after a delay of 40 to 60 min this effect was balanced by an inhibition of the motility of the ascending and transverse colon. Bromocriptine infused intravenously at doses of 10 to 40 μg kg−1 h−1 stimulated the motility of the whole colon but these effects were limited to the duration of the infusion (60 min).
Both propranolol (0.5 mg kg−1) and tolazoline (2 mg kg−1) failed to block the effects of dopamine and bromocriptine whereas phentolamine (0.1 mg kg−1) and prazosin (0.2 mg kg−1) partially reduced the inhibitory effects of dopamine on the proximal colon. Haloperidol at doses higher than 0.2 mg kg−1 and domperidone blocked the bromocriptine‐induced stimulation of colonic motility which was unaffected by previous treatment with α‐ and β‐adrenoceptor blocking agents.
These results suggest that in the dog, dopamine and bromocriptine stimulate colonic motility through specific dopamine receptors. However, they suggest that the inhibitory effects of dopamine on the proximal colon which are blocked by dopamine antagonists are also partially due to an effect on α1‐adrenoceptors.
Inhibition of calcium spikes and transmitter release by γ‐aminobutyric acid in the guinea‐pig myenteric plexus
Authors: Cherubini E. , North R. A. 
Published: July 2012

The effect of γ‐aminobutyric acid (GABA) (1 μM‐1 mM) on synaptic transmission in isolated myenteric ganglia of guinea‐pig ileum was investigated with intracellular recording techniques.
GABA (up to 1 mM) had no effect on the resting membrane potential and membrane conductance of S neurones.
GABA reduced the amplitude of the fast excitatory postsynaptic potential (e.p.s.p.) without changing the amplitude of the nicotinic response to ionophoretic application of acetylcholine (ACh). This effect was mimicked by baclofen (10–100 μM) and was not blocked by bicuculline (10 μM). The preparation did not become desensitized during prolonged GABA applications.
Cholinergic and non‐cholinergic slow e.p.s.ps evoked by single or repetitive presynaptic nerve stimulation were reduced in amplitude by GABA. GABA did not depress muscarinic responses to ionophoretic application of ACh.
GABA reduced the duration of the action potential in AH neurones in concentrations that did not affect the membrane potential or conductance. The effect was very marked when electrodes were filled with CsCl, and tetrodotoxin was in the supervising solution. This effect was also mimicked by baclofen, was insensitive to bicuculline and was not reduced with repeated application or GABA.
It is concluded that GABA inhibits release of ACh and the transmitter mediating the slow e.p.s.p. This effect may result from inhibition of an inward calcium current.
The anti‐ulcerogenic activity of the unripe plantain banana (Musa species)
Authors: Best Ralph , Lewis David A. , Nasser Nasser 
Published: July 2012

Various preparations of dried unripe plantain banana were found to be anti‐ulcerogenic against aspirin‐induced ulceration in the rat and were effective both as a prophylactic treatment and in healing ulcers already induced by aspirin. Ripe fruit bananas were inactive.
The active factor(s) were water soluble and were concentrated by extraction to approximately three hundred times that in the dried banana powder.
The anti‐ulcerogenic action of banana preparations appears to be due to their ability to stimulate the growth of gastric mucosa.
Aluminium hydroxide, cimetidine, prostaglandin E2, N6, O2‐dibutyryl adenosine 3′,5′ cyclic monophosphate but not 5‐hydroxytryptamine were also anti‐ulcerogenic when used prophylactically in rats but were ineffective in healing ulcers already formed by aspirin. These substances did not stimulate the growth of gastric mucosa.
Desensitization of the guinea‐pig urinary bladder by the enantiomers of adenylyl 5′‐(β,γ‐methylene)‐diphosphonate and by substance P
Authors: Hourani S.M.O. 
Published: July 2012

Adenosine 5′‐triphosphate (ATP), substance P (SP) and non‐cholinergic nerve stimulation contracted the guinea‐pig urinary bladder. SP and two poorly‐degradable analogues of ATP, the enantiomers of adenylyl 5′‐(β,γ‐methylene)‐diphosphonate (AMP‐PCP and L‐AMP‐PCP), were used to desensitize the guinea‐pig bladder.
Desensitization of the bladder by AMP‐PCP (50 μM) or by L‐AMP‐PCP (50 μM) abolished the responses to ATP, and inhibited the responses to non‐cholinergic nerve stimulation and to SP. The responses to histamine were unaffected.
Desensitization by SP (1 μM) inhibited the responses to SP itself, but not the responses to ATP, L‐AMP‐PCP or non‐cholinergic nerve stimulation.
These results suggest that SP may act partly by releasing ATP, and support the suggestion that ATP rather than SP is the non‐cholinergic stimulatory transmitter.