bluuebunny/crossref_metadata_2025_split huggingface dataset:
Similarity and dissimilarity of the vasoconstrictor effects of Bay K 8644 on coronary, femoral, mesenteric and renal circulations of dogs
Authors: Ishii Kuniaki , Sato Yoshinori , Taira Norio 
Published: July 2012

The effect of the dihydropyridine calcium agonist Bay K 8644 on the coronary, femoral, mesenteric and renal circulations was investigated and compared with that of noradrenaline in pentobarbitone‐anaesthetized dogs.
The left anterior descending coronary, femoral, cranial mesenteric and renal arteries were cannulated and their arterial beds perfused with autologous blood at a constant pressure slightly higher than the mean systemic arterial blood pressure. Bay K 8644 (0.1–300 nmol) and noradrenaline (0.1–300 nmol) were injected intra‐arterially.
Bay K 8644 decreased blood flow (vasoconstriction) in all 4 arterial beds. A maximum decrease was attained at 100 nmol and a further increase in dose did not appear to result in a further decrease in blood flow.
At maximum effects blood flow decreased to about 35% of the basal value in coronary, 30% in femoral, 20% in renal and 15% in mesenteric circulation.
Normalized ED50 values (ED50 divided by basal flow) of Bay K 8644 were 0.07 ± 0.02 nmol in the femoral, 0.08 ± 0.01 nmol in the coronary, 0.16 ± 0.06 nmol in the mesenteric and 0.55 ± 0.19 nmol in the renal circulation.
At 100 nmol, the values for the half‐duration of Bay K 8644 vasoconstrictor effects were about 196 s in the renal, 78 s in the mesenteric, 84 s in the femoral and 21 s in the coronary circulation.
Noradrenaline produced a dose‐dependent decrease in blood flow in femoral, mesenteric and renal circulations, and was about 2 times in femoral, 4 times in mesenteric and 9 times in renal circulation more potent than Bay K 8644.
Bay K 8644 produced slight increases in the maximum rate of rise of left ventricular pressure and intraluminal pressure of the ileum. However, the increases did not appear to impede blood flow.
Bay K 8644 produced slightly but significantly greater femoral vasoconstriction in normal dogs than in reserpine‐pretreated dogs.
From these results it was concluded that differences in potency, effectiveness and duration of the vasoconstrictor effects of Bay K 8644 between the 4 arterial beds probably derive from differences in characteristics of the smooth muscle of resistance vessels there. In arterial beds where α‐adrenoceptors are dominant, potentiation of the vasoconstrictor effect of endogenous catecholamines by Bay K 8644 seems to contribute to its vasoconstrictor effect.
The effect of ionic strength on cardiac muscarinic receptors
Authors: Burgen A.S.V. 
Published: July 2012

The binding of N‐methylscopolamine (NMS) and carbachol to muscarinic receptors in the rat heart has been measured as a function of ionic strength (μ).
The binding of NMS was reduced by 3.69 fold for a 10 fold increase in ionic strength.
The binding of carbachol was affected in two ways. Firstly, the proportions of the subsites were changed. Above μ = 0.5 M, the superhigh (SH) subsite was converted into the low(L) subsite and above μ = 0.8 M, the high (H) subsite was also converted into the L subsite. Therefore, at high ionic strength, no agonist‐determined subsites can be detected. In addition, increase in ionic strength reduced the binding of carbachol to all subsites and to a much greater extent than for NMS.
Membrane and contractile properties of the dog ciliary muscle
Authors: Ito Yushi , Yoshitomi Takeshi 
Published: July 2012

Membrane properties and excitation‐contraction coupling mechanisms of the dog ciliary muscle were investigated by use of microelectrode and isometric tension recording methods.
The mean resting membrane potential of the smooth muscle cell was − 59.6 ± 1.6 mV and the membrane was electrically quiescent. With applications of inward and outward current pulses, by the partition stimulating method (pulse duration, 1.0 s), electrotonic potentials, but not action potentials (spike) were evoked even in the presence of tetraethylammonium (TEA, 10 mM).
The space and time constants calculated from the current‐voltage relationship observed at various distances from the stimulating electrode were 0.43 ± 0.07 mm (± s.d. n = 5) and 82.5 ± 10.6 ms (± s.d. n = 4), respectively.
Electrical field stimulation of short duration (50–300 μ s) evoked excitatory junction potentials (e.j.ps) followed by twitch contraction, both of which were potentiated by neostigmine (10−7 M) and abolished by tetrodotoxin (TTX, 10−7 M) or atropine (10−6 M). However, e.j.ps of amplitude over 3–5 mV did not evoke action potentials.
Excess [K]o solution dose‐dependently depolarized the membrane (the maximum slope of the depolarizations produced by a tenfold increase in [K]o plotted on a log scale was 52.5 mV) and evoked contractions. Atropine (10−6 M) had no effect on the [K]o‐induced membrane depolarization, however, it greatly reduced the amplitude of [K]o‐induced contraction.
Nisoldipine (5 × 10−7 M) had no effect on the contraction evoked by field stimulation, however, this agent suppressed the [K]o‐induced contraction to 78.3 ± 6.8% of the control value. Combined application of nisoldipine and atropine completely inhibited the [K]o‐induced contraction.
Although the membrane depolarization evoked by carbachol (> 10−7 M) was small (10 mV depolarization at 10−5 M), the contraction evoked by 10−5 M carbachol was larger than that evoked by 118 mM [K]o (185 ± 50%, n = 9).
Ca‐free 3 mM EGTA‐containing solution did not alter the resting tension, but greatly reduced the carbachol‐induced contraction (to 8.6 ± 2.3% of the control value).
The present results indicate that the membrane of dog ciliary muscle behaves as an electrical syncytium, and that the contractile responses occur mainly through activation of the receptor‐operated Ca channels and partly through activation of voltage‐dependent Ca channels.
Chronic caffeine treatment reduces caffeine but not adenosine effects on cortical acetylcholine release
Authors: Corradetti R. , Pedata Felicita , Pepeu G. , Vannucchi Maria Giuliana 
Published: July 2012

The effects of both adenosine and caffeine on the release of acetylcholine (ACh) were investigated in slices of cerebral cortex taken from rats pretreated for 30 days with caffeine (100 mg kg−1 daily, dissolved in their drinking water) at rest and during electrical stimulation at frequencies of 0.2, 1 and 5 Hz. The effect of this treatment on adenosine binding sites was also investigated in cortical membranes using N‐cyclohexyl‐(3H]‐adenosine ([3H]‐CHA) as a ligand.
The chronic caffeine treatment did not change animal growth patterns. Spontaneous exploratory activity appeared to be increased at the 3rd day but was unchanged at the 30th day when compared with controls.
Caffeine‐treatment increased the number of high affinity binding sites for [3H]‐CHA by 64% over the control values. Low affinity binding site density and affinity constants were unaffected.
Adenosine 30 μM added to the superfusion fluid decreased electrically stimulated ACh release both in rats drinking tap water and rats drinking caffeine.
In rats drinking tap water, caffeine added to the superfusion fluid at a concentration of 50 μM enhanced ACh release, while at 0.5 mM it decreased ACh output from the slices. Both effects were abolished by pretreatment with caffeine in vivo.
The results indicate that prolonged consumption of high doses of caffeine causes changes in the responsiveness of cholinergic neurones to caffeine. The change is not shared by adenosine, through whose recognition sites caffeine is believed to act. It is therefore possible that the adaptive changes following repeated caffeine administration involve either only the coupler‐transducer mechanism activated by the antagonist, or effects unrelated to receptors.
Functional studies on human veins after storage at − 190°C
Authors: Müller‐Schweinitzer E. , Tapparelli C. , Victorzon M. 
Published: July 2012

Human saphenous veins were immersed in foetal calf serum containing 1.8 M dimethylsulphoxide, slowly frozen to −70°C and stored in liquid nitrogen (− 190°C).
Comparative in vitro studies on helical strips from unfrozen and frozen and thawed veins revealed that after thawing of frozen stored veins the contractile force development was unchanged, and the evidence suggested that the monoamine oxidase activity was unimpaired.
There was a good correlation between the pD2 values of various 5‐hydroxytryptamine receptor agonists and the blocking activities of various antagonists tested against 5‐hydroxytryptamine (5‐HT) and noradrenaline on unfrozen and frozen and thawed veins.
It is suggested that cryopreservation is a useful technique for storing human veins for pharmacological studies.
Characterization of the effects of (±)‐meptazinol, its individual enantiomers and N‐methyl meptazinol on food consumption in the rat
Authors: Jackson Helen C. , Sewell R.D.E. 
Published: July 2012

Both (±)‐meptazinol (2 mg kg−1) and levorphanol (1 mg kg−1) produced hyperphagia over a 4 h period after intraperitoneal injection in free feeding rats during the daylight phase.
The individual (+)‐ and (−)‐enantiomers of meptazinol (2 mg kg−1 i.p.) induced comparable increases in cumulative food intake.
N‐methyl meptazinol (2–10 mg kg−1 i.p.), the quaternary analogue of meptazinol, produced no modification of food intake though it increased food consumption when injected intracerebroventricularly (10–100 μg per animal).
Meptazinol and levorphanol hyperphagia was abolished by 1 mg kg−1 doses (i.p.) of the opioid antagonists naltrexone, naloxonazine and (−)‐Mr 1452 but not by its (+)‐enantiomer Mr 1453 which is not effective as an opioid antagonist.
Intracerebroventricular administration of the δ‐opioid receptor antagonist ICI 154,129 (10 μg per animal) suppressed meptazinol but not levorphanol hyperphagia.
It was concluded that meptazinol produces centrally mediated stereospecifically reversible hyperphagia through a μ‐opioid receptor mechanism common to levorphanol, and also through δ‐opioid receptor mechanism(s).
Antiarrhythmic effects of DPI 201‐106
Authors: Scholtysik Günter , Williams Frances M. 
Published: July 2012

The cardiotonic agent DPI 201‐106 (4‐[3‐(4‐diphenylmethyl‐1‐piperazinyl‐2‐hydroxypropyl]‐1H‐ indole‐2‐carbonitrile) which modifies the sarcolemmal Na+ channel gating system and has electrophysiological properties of class III antiarrhythmics was investigated for local anaesthetic and antiarrhythmic activity.
The compound action potential amplitude of cat cervical vagus nerves in vitro was decreased by DPI 201‐106 in a concentration‐dependent manner, the IC50 being 1.82 × 10−5 M. This was paralleled by a slowing in conduction velocity and demonstrates local anaesthetic effects.
Ventricular fibrillation which occurs in response to coronary artery reperfusion in rats was prevented by intravenous infusions of 0.3 mg kg−1 min−1 of DPI 201‐106.
The arrhythmogenic intravenous doses of aconitine in rats were increased following pretreatment with DPI 201‐106 in a dose‐dependent manner.
DPI 201‐106 did not protect against ouabain‐induced arrhythmias in guinea‐pigs.
The results demonstrate that DPI 201‐106 has local anaesthetic effects and is a potential antiarrhythmic.
The haemodynamic and metabolic effects of tolmesoxide with special reference to impaired myocardial function
Authors: Mackenzie John E. , Marshall Richard J. , Parratt James R. 
Published: July 2012

The haemodynamic, metabolic and regional blood flow effects of the vasodilator, tolmesoxide (1 mg kg−1 min−1 for 20 min by intravenous infusion) were examined in two groups of greyhound dogs anaesthetized with α‐chloralose and mechanically ventilated. One group of dogs was thoracotomized and subjected to acute coronary artery occlusion. In these dogs tolmesoxide was infused 2.5 h after occlusion when there was evidence of impaired myocardial function.
Tolmesoxide administration resulted in marked systemic hypotension which was associated with myocardial stimulation (increase in heart rate and LVdP/dtmax). These effects were less marked in thoracotomized dogs subjected to coronary artery occlusion. Cardiac stimulation was attenuated by pretreatment with the β‐adrenoceptor antagonist, atenolol.
Peripheral resistance and left ventricular end‐diastolic pressure (LVEDP) were reduced by tolmesoxide. In spite of the systemic hypotension, the marked reduction in LVEDP resulted in an enhanced subendocardial driving pressure and an increased blood flow to ischaemic regions of the left ventricular wall as measured with Xe133 clearance. Blood flow to normal regions of the left ventricular wall was also increased by tolmesoxide.
A metabolic and respiratory acidosis may have contributed to the haemodynamic effects of tolmesoxide. Plasma renin levels were significantly elevated by the drug.
Tolmesoxide administration thus resulted in cardiac stimulation, reduced both pre‐load and after‐load, yet maintained coronary and pulmonary perfusion. This haemodynamic profile of tolmesoxide would explain the beneficial effects obtained with this drug in the treatment of cardiac failure.
Electrophysiological effects of amoxapine in untreated and in amoxapine‐pretreated rat atria
Authors: Delgado C. , Manzanares J. , Tamargo J. , Valenzuela C. 
Published: July 2012

The effects of amoxapine (10−7 − 10−4 M) have been studied in rat atrial fibres obtained from untreated animals and animals pretreated for 28 days with amoxapine (10 mg kg−1, i.p.).
In untreated atria amoxapine reduced atrial rate, contractile force and df/dtmax, prolonged the sinus node recovery time and decreased atrial excitability.
Amoxapine also decreased amplitude and Vmax of the upstroke, prolonged the duration of the action potential (APD) and effective refractory period (ERP) and reduced the resting membrane potential.
During the treatment with amoxapine behavioural and cardiovascular adverse effects, including hypotension, tachycardia and prolongation of the Q‐Tc, were observed. However, with the exception of the ERP which was significantly prolonged in pretreated atria, pretreatment with amoxapine did not modify the control values of the measured parameters compared to those obtained in untreated atria.
Further addition of amoxapine produced similar changes in both pretreated and untreated atria. However, in contrast to untreated atria, in pretreated atria the prolongation of the ERP produced by amoxapine exceeded the prolongation of the APD and thus, the ERP/APD ratio increased. The decrease in atrial excitability was also more marked in pretreated than in untreated atria.
Amoxapine inhibited the slow action potentials and contractions induced by isoprenaline in K‐depolarized atria.
It is concluded that the electrophysiological effects of amoxapine on rat atrial fibres are similar to those described for other tricyclic antidepressants. Possible explanations for the lower cardiodepressant activity of amoxapine are discussed.
Effect of prostaglandin D2 on histamine‐induced weals in human skin
Authors: Barnes Vanessa F. , Heavey Dennis J. 
Published: July 2012

The effect of prostaglandin D2 (PGD2) on weal response to intradermal injection of histamine was examined in normal volunteers.
Co‐injection of variable amounts of PGD2 with a fixed dose of histamine (2.5 nmol) was made so that the molar ratio of histamine: PGD2 covered the range 15 to 1215. There was no significant effect of PGD2 on weal area.
PGD2, present at a 50 times lower concentration than histamine, had no effect on either the dose‐response curves for the histamine‐induced weal area or the forearm weal volume response to 2.5 nmol histamine.
It is concluded that PGD2, when present at the relative amounts found in vitro and in vivo, has no effect on the weal response to histamine in man.
Central β‐adrenoceptors can modulate 5‐hydroxytryptamine‐induced tremor in rats
Authors: Hallberg Heléne 
Published: July 2012

The effects of two β2‐adrenoceptor agonists with different lipophilicities were studied on tremor induced by L‐5‐hydroxytryptophan (L‐5‐HTP) in pargyline‐ and carbidopa‐pretreated rats.
Tremor was recorded and analysed by an objective method based on accelerometry.
Clenbuterol, a lipophilic β2‐selective agonist, dose‐dependently enhanced tremor intensity, whereas the hydrophilic β2‐agonist terbutaline had no effect.
The clenbuterol‐induced enhancement of tremor was completely abolished by the β2‐selective antagonist ICI 118,551 but unchanged by the β1‐selective antagonist metoprolol.
The results suggest that centrally located β2‐adrenoceptors can mediate a modulation of 5‐hydroxytryptamine‐induced tremor in rats.
High affinity binding of [3H]‐tyramine in the central nervous system
Authors: Vaccari Andrea 
Published: July 2012

Optimum assay conditions for the association of [3H]‐para‐tyramine ([3H]‐pTA) with rat brain membranes were characterized, and a saturable, reversible, drug‐specific, and high affinity binding mechanism for this trace amine was revealed.
The binding capacity (Bmax) for [3H]‐pTA in the corpus striatum was approximately 30 times higher than that in the cerebellum, with similar dissociation constants (KD).
The binding process of [3H]‐pTA involved the dopamine system, inasmuch as (a) highest binding capacity was associated with dopamine‐rich regions; (b) dopamine and pTA equally displaced specifically bound [3H]‐pTA; (c) there was a severe loss in striatal binding capacity for [3H]‐pTA and, reportedly, for [3H]‐dopamine, following unilateral nigrostriatal lesion; (d) acute in vivo reserpine treatment markedly decreased the density of [3H]‐pTA and, reportedly, of [3H]‐dopamine binding sites.
In competition experiments [3H]‐pTA binding sites, though displaying nanomolar affinity for dopamine, revealed micromolar affinities for the dopamine agonists apomorphine and pergolide, and for several dopamine antagonists, while having very high affinity for reserpine, a marker for the catecholamine transporter in synaptic vesicles.
The binding process of [3H]‐pTA was both energy‐dependent (ouabain‐sensitive), and ATP‐Mg2+‐insensitive; furthermore, the potencies of various drugs in competing for [3H]‐pTA binding to rat striatal membranes correlated well (r = 0.96) with their reported potencies in inhibiting [3H]‐dopamine uptake into striatal synaptosomes.
It is concluded that [3H]‐pTA binds at a site located on/within synaptic vesicles where it is involved in the transport mechanism of dopamine.
Tetrodotoxin‐sensitive, K+‐induced relaxation of guinea‐pig isolated trachealis in the presence of Ca2+‐entry blocking drugs, Ca2+‐free solution and after polyamine exposure
Authors: Chideckel Elliott W. , Fedan Jeffrey S. , Mike Pamela 
Published: July 2012

We have previously observed a paradoxical relaxant effect of K+ on guinea‐pig isolated trachealis after exposure to polyamines. The purpose of the present study was to evaluate whether the relaxation involved a reduction in the entry of extracellular Ca2+. We therefore investigated the effect of K+ in the presence of Ca2+‐entry blocking drugs and in the presence of Ca2+‐free solution.
In the presence of nifedipine (10−5 M), verapamil (10−5 M) or diltiazem (10−5 M), K+ (30 mM) induced relaxation of the trachealis muscle. The relaxation to K+ was not blocked by ouabain (10−6 M), propranolol (10−6 M), or indomethacin (10−6 M).
A relaxation in response to K+ was also observed in Ca2+‐free solution, (with tone induced by methacholine), an effect not blocked by propranolol or ouabain.
Tetraethylammonium (30 mM) (TEA), which ordinarily evokes contractile responses, induced trachealis relaxation in the presence of verapamil or nifedipine. The relaxation was unaltered by ouabain or propranolol.
Tetrodotoxin (10−6 M) (TTX) blocked 65% of the K+‐induced relaxation in the presence of nifedipine and 100% of K+‐induced relaxation either in a Ca2+‐free solution or after polyamine exposure. TTX was without effect on TEA‐induced relaxation after Ca2+‐entry blocking drugs.
Atropine (10−6 M) or hexamethonium (10−6 M) did not affect K+‐induced relaxation after polyamine exposure.
The concentration‐response curve for K+‐induced contraction in normal modified Krebs‐Henseleit solution was shifted to the left by TTX.
It is concluded: (a) K+ has a direct effect on the trachealis causing contraction and an indirect effect, mediated by neurotransmitter release, causing relaxation. This latter effect is exposed when the direct effect is inhibited by Ca2+‐entry blocking drugs, Ca2+‐free solution or polyamine exposure; the indirect effect is non‐adrenergic, non‐cholinergic and not via ganglionic transmission; (b) the TEA‐induced relaxation and a component of the K+‐induced relaxation after Ca2+ blocking drugs cannot be explained by neurotransmitter release; (c) polyamines may act as naturally occurring Ca2+ antagonists.
Glutamate‐induced increase in intracellular Ca2+ concentration in isolated hippocampal neurones
Authors: Kudo Yoshihisa , Ogura Akihiko 
Published: July 2012

A system for real‐time quantitative monitoring of intracellular free calcium ion concentration ([Ca2+]i) on a single cell basis was developed by the combination of a fluorescent Ca2+ indicator fura‐2, a fluorescence microscope, a video‐camera and photometrical devices. It was applied to rat individual hippocampal neurones under culture for detection of L‐glutamate‐induced alterations in the [Ca2+]i level.
L‐Glutamate (0.01–100 μM) induced a dose‐dependent elevation of the [Ca2+]i. The [Ca2+]i in the rat hippocampal neurone was found to be around 30 nM in the resting state, and was increased up to 500 nM by the application of 100 μM L‐glutamate. N‐methyl‐D‐aspartate, kainate and quisqualate in a concentration of 10 μM also increased the [Ca2+]i level in the same single neurone, but their efficacy varied between individual cells.
The L‐glutamate‐induced [Ca2+]i elevation was abolished after removal of extracellular Ca2+ and was much reduced by Mg2+ (3 mM). The increase was, however, still observed in a Na+‐free medium.
The L‐glutamate‐induced [Ca2+]i elevation was not affected substantially after treatment with nitrendipine (10 μM) which blocked the increase in [Ca2+]i induced by an isotonic high KCl‐medium (50 mM).
The present results suggest that the L‐glutamate‐induced [Ca2+]i elevation in the hippocampal neurone is due to an influx of Ca2+ through both L‐glutamate receptor‐coupled and voltage‐sensitive ionic channels.
Atriopeptin II‐induced relaxation of rabbit aorta is potentiated by M&B 22,948 but not blocked by haemoglobin
Authors: Martin William , Morgan Robert O. , Smith Jerry A. , White David G. 
Published: July 2012

We examined the effects of haemoglobin (which inhibits the vascular responses to stimulation of soluble guanylate cyclase) and of M&B 22,948 (which selectively inhibits cyclic GMP phosphodiesterase) on the relaxation induced in rabbit aorta by the atrial natriuretic peptide, atriopeptin II (which stimulates particulate guanylate cyclase).
Pretreatment with M&B 22,948 (100 μM) produced a 2.3 fold potentiation of atriopeptin II‐induced relaxation of endothelium‐denuded rings of rabbit aorta.
Pretreatment with haemoglobin (10 μM) had no effect on the relaxation or the 10.9 fold increase in cyclic GMP content induced by atriopeptin II in endothelium‐denuded rings of rabbit aorta.
The potentiation by M&B 22,948 suggests a causal role for cyclic GMP in mediating atriopeptin II‐induced vasodilatation of rabbit aorta.
The inability of haemoglobin to block the atriopeptin II‐induced rise in cyclic GMP suggests that it does not block stimulation of particulate guanylate cyclase. Thus, it is unlikely that a ferrous haem‐containing receptor site is involved in the activation of the particulate form of guanylate cyclase as it is with soluble guanylate cyclase.