bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRH‐Induced blood flow and mean arterial pressure changes in the rabbit are not dependent on the anaesthetic used
Authors: Hugoson‐Seligsohn Eva E. , Koskinen Lars‐Owe D. 
Published: July 2012

The effects of thyrotropin releasing hormone (TRH) on regional cerebral blood flow were studied in rabbits anaesthetized with pentobarbitone or ketamine. The blood flow was determined with the labelled microsphere method before and after the i.v. administration of either 50 μg kg−1 or 2 mg kg−1 TRH.
In order to measure the cerebral O2 consumption the arteriovenous difference in oxygen saturation in the brain (CAVOD) was measured before and after the administration of 2 mg kg−1 TRH.
In animals under pentobarbitone anaesthesia 50 μg kg−1 TRH elicited an increase in mean arterial blood pressure (MAP) of about 1 kPa and 2 mg kg−1 TRH elevated the MAP by about 2 kPa. With ketamine as the anaesthetic the corresponding values were 0.5 kPa and 7 kPa, respectively. TRH induced significant vasoconstriction in several peripheral tissues.
The total cerebral blood flow (CBFtot) increased from 54 ± 4 to 78 ± 5 g min−1 100 g−1 after the administration of 50 μg kg−1 TRH in pentobarbitone‐anaesthetized animals. An even greater effect was elicited by 2 mg kg−1 TRH, from 48 ± 6 to 113 ± 19 g min−1 100 g−1. In ketamine‐anaesthetized rabbits, 50 μg kg−1 TRH tended to enhance the CBFtot and 2 mg kg−1 increased it from 71 ± 6 to 141 ± 19 g min−1 100g−1.
In animals anaesthetized with pentobarbitone, the CAVOD decreased from 47.3 ± 1.7% to 35.1 ± 2.2% at 3 min after TRH delivery, and then gradually increased to the control level. In animals under ketamine anaesthesia the CAVOD decreased from 63.3 ± 2.0% to 45.2 ± 7.4% after the administration of 2 mg kg−1 TRH.
It is concluded that TRH elicits cerebral vasodilatation in excess of that required by the change in cerebral metabolism which may have taken place. The pattern of responses was similar to that produced in rabbits under urethane anaesthesia.
Negative inotropic activity of antilaminin IgG: participation of cholinergic mechanisms
Authors: Bacman Sandra , Borda Enri , Denduchis Berta , Lustig Livia , Sterin‐Borda Leonor 
Published: July 2012

Antilaminin IgG decreased the dF/dt of mouse isolated atria and inhibited the mechanical effect of acetylcholine in a non‐competitive fashion.
Inhibitors of nicotinic and muscarinic cholinoceptors impaired the negative inotropic action of antilaminin IgG in mouse isolated atria. Hemicholinium and tetrodotoxin also reduced the response while the antihistamine, pyrilamine was without effect.
These results suggest that antilaminin IgG modulates cholinergic function in mouse isolated atria. Possible mechanisms are discussed.
Reduction of cephalic arteriovenous shunting by ergotamine is not mediated by 5‐HT1‐like or 5‐HT2 receptors
Authors: Bom Anton H. , Heiligers Jan P.C. , Saxena Pramod R. , Verdouw Pieter D. 
Published: July 2012

The potent, antimigraine drug ergotamine has affinity for both 5‐HT1 and 5‐HT2 binding sites and constricts arteriovenous anastomoses. Since 5‐HT also constricts arteriovenous anastomoses (mainly via 5‐HT1‐like receptors), this study investigates the involvement of 5‐HT receptors in the ergotamine‐induced reduction of arteriovenous shunting in the carotid circulation of the cat and pig.
In the cat, ergotamine (3, 10 and 30 μg kg−1, i.v.) reduced carotid blood flow, predominantly by a reduction in arteriovenous anastomotic blood flow. Pretreatment with ketanserin (0.5 mg kg−1, i.v.) or methiothepin (1 mg kg−1, i.v.) did not antagonize the effects of ergotamine.
In the pig, ergotamine (2.5, 5, 10 and 20 μg kg−1, i.v.) also reduced carotid blood flow and arteriovenous shunting, which was not affected by pretreatment with methiothepin (1 mg kg−1, i.v.).
These results suggest that the reduction by ergotamine in the shunting of carotid arterial blood via cephalic arteriovenous anastomoses is not mediated by 5‐HT1‐like or 5‐HT2 receptors.
Defibrotide reduces infarct size in a rabbit model of experimental myocardial ischaemia and reperfusion
Authors: Thiemermann Christoph , Thomas G. Roger , Vane John R. 
Published: July 2012

Defibrotide, a single‐stranded polydeoxyribonuncleotide obtained from bovine lungs, has significant anti‐thrombotic, pro‐fibrinolytic and prostacyclin‐stimulating properties.
The present study was designed to evaluate the effects of defibrotide on infarct size and regional myocardial blood flow in a rabbit model of myocardial ischaemia and reperfusion.
Defibrotide (32 mg kg−1 bolus + 32 mg kg−1 h−1, i.v.) either with or without co‐administration of indomethacin (5 mg kg−1 × 2, i.v.) was administered 5 min after occlusion of the left anterior‐lateral coronary artery and continued during the 60 min occlusion and subsequent 3 h reperfusion periods.
Defibrotide significantly attenuated the ischaemia‐induced ST‐segment elevation and abolished the reperfusion‐related changes (R‐wave reduction and Q‐wave development) in the electrocardiogram. In addition, defibrotide significantly improved myocardial blood flow in normal and in ischaemic, but not in infarcted sections of the heart. The improvement in blood flow in normal perfused myocardium, but not in the ischaemic area was prevented by indomethacin.
Although the area at risk was similar in all animal groups studied, defibrotide treatment resulted in a 51% reduction of infarct size. Indomethacin treatment abolished the reduction of infarct size seen with defibrotide alone.
The data demonstrate a considerable cardioprotective effect of defibrotide in the reperfused ischaemic rabbit myocardium. This effect may be related, at least in part, to a stimulation of endogenous prostaglandin formation. Other possible mechanisms are discussed.
Mechanism of xanthine‐induced relaxation of guinea‐pig isolated trachealis muscle
Authors: Ogawa K. , Takagi K. , Satake T. 
Published: July 2012

Four 3‐alkylxanthines (3‐methylxanthine, 3‐n‐propylxanthine (enprofylline), 3‐n‐butylxanthine and 3‐iso‐butylxanthine) and four 1‐methyl‐3‐alkylxanthines (1‐methyl‐3‐methylxanthine (theophylline), 1‐methyl‐3‐n‐propylxanthine, 1‐methyl‐3‐n‐butylxanthine and 1‐methyl‐3‐iso‐butylxanthine (IBMX)), were compared in terms of cyclic AMP phosphodiesterase (PDE) inhibition and trachealis muscle relaxation. The relationship between xanthine structure and cyclic AMP PDE inhibition was also studied.
Xanthine induced relaxation of guinea‐pig isolated trachealis muscle was measured against spontaneous tone.
The four 1‐methyl‐3‐alkylxanthines were each significantly more potent than the corresponding 3‐alkylxanthines in relaxing the isolated trachealis muscle. The 1‐methyl‐3‐alkylxanthines were similarly more potent than the corresponding 3‐alkyl derivatives in inhibiting low Km cyclic AMP PDE. There was a strong positive correlation between low Km cyclic AMP PDE inhibition and the tracheal smooth muscle relaxation evoked by the xanthine derivatives.
Since methylation of the 1‐position of each 3‐alkylxanthine increased the potency of the derivative in inhibiting low Km cyclic AMP PDE and in relaxing trachealis muscle and since a strong positive correlation was observed between the relaxant EC50 and the Ki value of each xanthine derivative, it is suggested that low Km cyclic AMP PDE inhibition by xanthines plays an important role in their tracheal relaxant effect.
Subclassification of atrial and intestinal muscarinic receptors of the rat—direct binding studies with agonists and antagonists
Authors: Brunner F. 
Published: July 2012

Although extensively investigated, the extent of differences between receptors mediating negative inotropic and chronotropic responses is still unclear. In the present study atrial and intestinal muscarinic receptors were identified by [3H]‐N‐methyl‐scopolamine ([3H]‐NMS) binding and the affinities of some presumably inotropy‐ or chronotropy‐selective agonists and several antagonists determined.
All the agonists tested showed similar affinity for right and left atrial receptors. Accepting an affinity difference of 0.4 log units as experimental error, none of the agonists tested was selective for either atrium.
Affinity differences of the cardioselective antagonists himbacine, AF‐DX 116 and methoctramine and the M1‐selective antagonist dicyclomine for right and left atrial muscarinic receptors were also minimal (less than 2 fold selective). When compared to intestinal receptors, AF‐DX 116 was 3 to 4 fold, methoctramine 10 to 13 fold selective and himbacine and dicyclomine non‐selective.
These data provide evidence for differences between atrial and intestinal but not between right and left atrial muscarinic receptors.
Presynaptic muscarinic receptors inhibiting endogenous noradrenaline release in the portal vein of the freely moving rat
Authors: Remie R. , Coppes R.P. , Zaagsma J. 
Published: July 2012

In the portal vein of the freely moving unanaesthetized rat, the existence of presynaptically located inhibitory muscarinic receptors was investigated by use of the muscarinic agonist methacholine (MCh)
Infusion of MCh (0.3 μg min−1) did not significantly inhibit the endogenous noradrenaline (NA) overflow in portal plasma. However, after inducing high intra‐synaptic concentrations of NA by blocking the presynaptic α2‐adrenoceptors with yohimbine (1 mg kg−1), MCh (0.3 μg min−1) was able to reduce the yohimbine‐induced enhanced NA overflow by 38%.
The MCh‐induced inhibition was almost completely abolished after blockade of the presynaptic muscarinic receptors with atropine (0.6 mg kg−1).
During electrical stimulation of the portal vein nervous plexus the evoked NA overflow was strongly inhibited (95%) during MCh‐infusion (0.3 μg min−1). Again atropine (0.6 mg kg−1) was able to reverse this inhibition.
These results show the existence of presynaptic muscarinic receptors inhibiting endogenous NA overflow from the portal vein nervous plexus under conditions of enhanced sympathetic activity in the freely moving rat.
Ketamine‐induced relaxation in intact and skinned smooth muscles of the rabbit ear artery
Authors: Kanmura Y. , Yoshitake J. , Casteels R. 
Published: July 2012

The effects of ketamine, an intravenous anaesthetic, on the rabbit ear artery were investigated by measuring the tension in intact and saponin‐treated skinned smooth‐muscle fibres.
Ketamine dose‐dependently inhibited contractions of intact smooth‐muscle fibres induced by high K+ solution and by noradrenaline (NA) or histamine in Krebs solution. This drug similarly attenuated both phasic and tonic contractions induced by high K+ solution.
Ketamine also inhibited NA‐ or histamine‐induced contractions in Ca2+‐free solution containing 2 mm EGTA, but it did not affect the caffeine‐induced contraction in this solution.
Because the pCa‐tension relationship of saponin‐treated skinned smooth‐muscle fibres was not affected, it can be proposed that ketamine does not have an effect on the contractile proteins.
In the presence of 5 mm NaN3, 20 μm inositol 1,4,5‐trisphosphate (InsP3) or 25 mm caffeine produced a contraction in skinned smooth‐muscle fibres after accumulation of Ca2+ by intracellular stores. Analysis of the InsP3‐ or caffeine‐induced contractions indicates that ketamine does not have an effect on the Ca2+ accumulation into and Ca2+ release from the intracellular stores.
These results indicate that the relaxant effects produced by ketamine in the rabbit ear artery are not likely to be due to an intracellular action. The inhibitory effects of ketamine could be caused by a decrease of the Ca2+ influx through the plasma membrane or interference with the process of signal transduction between receptors on the plasma membrane and intracellular stores.
The effect of relaxants working through different transduction mechanisms on the tonic contraction produced in rat aorta by 4β‐phorbol dibutyrate
Authors: Obianime A.W. , Dale M. Maureen 
Published: July 2012

We have examined the effects of a range of smooth muscle relaxants on the maintained contractions produced in rat aortic rings by the protein kinase C activator, 4β‐phorbol dibutyrate; these effects were compared with those on the contraction induced by the selective α1‐adrenoceptor agonist, methoxamine. The phorbol ester, at 0.3 μm, gave a sustained contraction which was, on average, of approximately the same magnitude as the maximum contraction produced by methoxamine, 10 μm.
The β‐adrenoceptor agonist, isoprenaline (0.01–1 μm) caused a dose‐related relaxation of the methoxamine‐induced contraction but had no effect on the contraction induced by the phorbol ester.
An activator of adenylate cyclase, forskolin (0.01–1 μm) produced a dose‐related relaxation of the methoxamine‐induced contraction and at 0.01–10 μm caused relaxation of the contraction induced by the phorbol ester. Similar results were obtained with the potassium channel activator, cromakalim (0.001–10 μm).
An activator of guanylate cyclase, sodium nitroprusside (0.001–100 μm) caused a dose‐related relaxation of both the methoxamine‐induced and the phorbol ester‐induced contraction, being more effective on the former than on the latter. Similar results were obtained with enprofylline (11000 μm).
Methoxamine (10 nM‐100 μm), given cumulatively, caused a dose‐related contractile response. Pretreatment with isoprenaline (1 μm), enprofylline (10 μm) and nicorandil (1 μm) resulted in partial decrease of the subsequent response to methoxamine, while nicorandil (10 μm), forskolin (1 μm), sodium nitroprusside (10 μm) and cromakalim (1 μm) totally abolished it.
The phorbol ester, given cumulatively, caused increasing contraction in the concentration range 30 nM‐10 μm. Pretreatment with forskolin (1 μm), sodium nitroprusside (10 μm), isoprenaline (1 μm), enprofylline (10 μm), nicorandil (1 μm or 10 μm), or cromakalim (1 μm or 10 μm), resulted in partial decrease of the subsequent response to 4β‐phorbol dibutyrate.
These results are discussed in the light of the suggestion that protein kinase C may have a role in the ‘latch‐bridge’ phase of smooth muscle contraction, and that inappropriate activation of protein kinase C may contribute to the pathogenesis of hypertension and other conditions involving vasospasm.
Central nervous system kinin receptors and the hypertensive response mediated by bradykinin
Authors: Lindsey C.J. , Nakaie C.R. , Martins D.T.O. 
Published: July 2012

Bradykinin (Bk) administered intracerebroventricularly to the rat causes an increase in arterial pressure.
Analogues of Bk with agonist and antagonist activity were injected, over a wide dose‐range, into the posterior region of the fourth ventricle of unanaesthetized rats implanted with permanent ventricular canullae, and blood pressure was measured directly from the abdominal aorta.
The analogues Ile‐Ser‐Bk (T‐kinin) and Lys‐Lys‐Bk, which interact with both B1 and B2 Bk receptors, produced pressor effects similar to those of Bk, although of greater duration, whereas des‐Arg9‐Bk, a B1 ‐receptor agonist, had no effect.
The B1‐antagonist des‐Arg9‐[Leu8]‐Bk did not alter the Bk pressor response, but D‐Arg‐[Hyp3, Thi5,8,D‐Phe7]‐Bk, which interacts both with B1‐ and B2‐receptors blocked the responses to Bk, T‐kinin and Lys‐Lys‐Bk and caused parallel shifts to the right of the Bk dose‐response curves. Neither antagonist, by itself, had any effect on blood pressure.
It is concluded that the central pressor response to Bk is mediated by receptors of the B2 subtype.
The involvement of lactate and calcium as mediators of the electrical and mechanical responses of the myocardium to conditions of simulated ischaemia
Authors: Northover B.J. 
Published: July 2012

Rat isolated and superfused atria were exposed to a lactate‐containing solution simulating the composition of extracellular fluid during myocardial ischaemia (SI).
Atria subjected to SI showed a decreased adenosine 5′‐triphosphate (ATP) content, a rise in diastolic tension, a diminished conduction velocity of action potentials and shortened refractory periods. All these changes were less pronounced during lactate‐free SI.
Atria preloaded with calcium displayed exaggerated responses measured electrically and mechanically during exposure to SI, whereas atria previously depleted of calcium displayed diminished electrical and mechanical responses to SI. Neither calcium loading nor calcium depletion modified the SI‐induced depletion of the atrial stores of ATP.
Sulphinpyrazone protected atria against all aspects of the response to SI, but failed to protect the muscle under conditions of lactate‐free SI. It is concluded that during SI, sulphinpyrazone protects against a lactate‐mediated inhibition of the glycolytic synthesis of ATP.
Flufenamate exaggerated all responses of the atria to SI. These deleterious actions were still observed during lactate‐free SI. It is concluded that flufenamate inhibits the synthesis of ATP in the mitochondria.
Physical dependence on diazepam in the dog: precipitation of different abstinence syndromes by the benzodiazepine receptor antagonists Ro 15–1788 and ZK 93426
Authors: Löscher Wolfgang , Hönack Dagmar , Faßbender Christian P. 
Published: July 2012

The effects of the benzodiazepine receptor antagonists Ro 15–1788 (flumazenil) and the β‐carboline ZK 93426 were compared in dogs before and after chronic treatment with diazepam.
In diazepam‐naive dogs, the most prominent behavioural alterations occurring during or after i.v. infusion of Ro 15–1788 up to a dose of 20 mg kg−1 were transient sedation, ataxia, and ‘hot foot’ behaviour, whereas behavioural alterations observed after ZK 93426 were not different from those observed after i.v. infusion of vehicle alone. This indicates that, in contrast to Ro 15–1788, ZK 93426 did not exert partial agonistic activity at benzodiazepine receptors.
In dogs treated 3 times daily with diazepam, 1 mg kg−1 orally, for 1 week, both benzodiazepine antagonists precipitated abstinence symptoms but the number and severity of withdrawal signs induced by Ro 15–1788 were greater than with ZK 93426.
In dogs treated 3 times daily with diazepam, 2 mg kg−1 orally, for 2 weeks, severe abstinence symptoms were precipitated in all animals by infusion of either antagonist but differences were found in the type of the symptoms: Ro 15–1788 induced rigid postures or rigid walking with increased muscle tone, tremor, twitches and jerks, whereas ZK 93426 did not alter motility but induced generalized myoclonic jerks and tonic‐clonic seizures. A generalized tonic‐clonic seizure was also observed in one dog of the trial with infusion of Ro 15–1788.
Plasma level determinations during chronic treatment with diazepam showed marked accumulation of the major active metabolite desmethyldiazepam, whereas diazepam levels were at least 15 times lower, which might suggest that desmethyldiazepam was responsible for the development of physical dependence on diazepam.
Potassium channel blockers differentially affect carbachol and (−)‐N6‐phenylisopropyladenosine on guinea‐pig atria
Authors: de Biasi Mariella , Froldi Guglielmina , Ragazzi Eugenio , Pandolfo Luisa , Caparrotta Laura , Fassina Guliana 
Published: July 2012

The effect of three different potassium channel blockers (tetraethylammonium, TEA; 4‐aminopyridine, 4‐AP; and apamin) and of variations in the concentration of K+ and Ca2+ in the medium, have been studied on the responses of guinea‐pig isolated atria to (−)‐N6‐phenylisopropyladenosine (R‐PIA), a stable adenosine A1‐receptor agonist, and to carbachol, a muscarinic agonist. R‐PIA and carbachol showed the same negative inotropic effects over a similar range of concentrations (3–300 μm), both in spontaneously beating and in electrically driven atria.
TEA (0.1 to 20 mm) and 4‐AP (0.3 to 3 mm), both antagonized the negative inotropic and chronotropic effects of carbachol in a concentration‐dependent manner. In contrast, these compounds failed to inhibit the effects induced by R‐PIA. Apamin, a specific blocker of a low conductance Ca2+‐activated K+ channel, was ineffective in accordance with the absence of these channels in atrial tissue.
TEA (0.1 to 20 mm) inhibited the negative inotropic effect of carbachol, but not that of R‐PIA, in atria paced and depolarized by a high K+ medium (22mm). In this preparation Na+ current is abolished and the contraction induced by noradrenaline and electrical stimulation is solely dependent on Ca2+ influx currents.
Stepwise addition of Ca2+ to a calcium‐depleted perfusing medium of electrically driven atria, induced a positive inotropic effect which was inhibited by R‐PIA. In contrast, carbachol had no effect.
In agreement with our previous study, the data suggest that R‐PIA acts on isolated atria by inhibiting Ca2+ influx through L‐channels.
Differential release of histamine and eicosanoids from human skin mast cells activated by IgE‐dependent and non‐immunological stimuli
Authors: Benyon R. Christopher , Robinson Clive , Church Martin K. 
Published: July 2012

Cells were dispersed from human foreskin using a mixture of collagenase and hyaluronidase and separated into mast cell‐depleted (<1%) or enriched (>75%) preparations by density‐gradient centrifugation.
Challenge of gradient fractions with ∍‐chain‐specific anti‐human IgE stimulated the release of histamine, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The release of eicosanoids was significantly correlated with that of histamine, suggesting that they are derived from the mast cell population of the dispersate. In highly purified (76.2 ± 4.2%) mast cell preparations, maximum net release of histamine, PGD2 and LTC4 was 3432 ± 725, 84.9 ± 10.8 and 6.6 ± 1.2 pmol/106 nucleated cells.
The non‐immunological stimuli substance P, vasoactive intestinal peptide (VIP), somatostatin, compound 48/80, morphine and poly‐L‐lysine released similar amounts of histamine to anti‐IgE, but 12 to 21 fold less PGD2 and LTC4.
These studies suggest that IgE‐dependent and non‐immunological stimuli activate human skin mast cells by different secretory mechanisms, a hypothesis supported by our previous findings of differences in Ca2+ requirements and time‐course of histamine release. Activation by the non‐immunological mechanism may be of importance in vivo due to the close anatomical association between skin mast cells and dermal nerve‐terminals containing neuropeptides.
Block of sodium channels by psychotropic drugs in single guinea‐pig cardiac myocytes
Authors: Ogata Nobukuni , Narahashi Toshio 
Published: July 2012

Effects of imipramine and haloperidol on voltage‐gated sodium channels were investigated in guinea‐pig isolated ventricular myocytes by the whole‐cell patch clamp technique. Some additional experiments were also performed with chlorpromazine for the purpose of comparison.
All test drugs in micromolar concentrations suppressed the amplitude of peak sodium current associated with step depolarization from a holding potential of −140 mV in a reversible manner. The order of potency was chlorpromazine > imipramine > haloperidol.
Dose‐response curves obtained with a holding potential of −140 mV were best fitted by 2:1 stoichiometry in all three drugs and were shifted in the direction of lower concentrations when a holding potential of −90 mV was used.
The drug‐induced block was not associated with any change in the time courses of sodium current activation and inactivation.
Steady‐state sodium channel inactivation curve was shifted in the direction of more negative potentials by the drugs.
All three drugs also produced marked use‐dependent block as demonstrated by a cumulative increase in the block during a train of depolarizing pulses.
The use dependence was due to a higher affinity of the drugs for the inactivated state of sodium channels than the resting state and to a very slow repriming of the drug‐bound sodium channels from inactivation.
The steady‐state and use‐dependent block of voltage‐gated sodium channels by psychotropic drugs may contribute to their cardiotoxic and perhaps antiarrhythmic effect.