bluuebunny/crossref_metadata_2025_split huggingface dataset:
The antiarrhythmic and cardiac electrophysiological effects of buprenorphine
Authors: Boachie‐Ansah G. , Sitsapesan R. , Kane K.A. , Parratt J.R. 
Published: July 2012

The effects of buprenorphine, given intravenously, on the incidence and severity of early acute coronary artery occlusion‐induced arrhythmias were examined in anaesthetised rats. The electrophysiological effects of buprenorphine were also examined in sheep Purkinje fibres and rat papillary muscles, superfused in vitro with either a normal or a hypoxic, hyperkalaemic and acidotic physiological salt solution (PSS).
In anaesthetised rats subjected to acute coronary artery occlusion, pretreatment with buprenorphine (1 mg kg−1 i.v.) markedly reduced the incidence of ventricular extra‐systoles during the initial 30 min post‐occlusion period. The incidence of ventricular fibrillation (VF) was also significantly reduced from 56% to 10%.
At the antiarrhythmic dose (1 mg kg−1), buprenorphine also attenuated the sudden fall in systemic arterial blood pressure induced by acute coronary artery ligation.
In normal sheep Purkinje fibres and rat papillary muscles, buprenorphine (10−6‐10−5 m) significantly reduced the action potential height and maximum rate of depolarisation of phase zero (MRD) and prolonged the duration of the action potential.
Superfusion of sheep Purkinje fibres and rat papillary muscles with a hypoxic, hyperkalaemic and acidotic PSS resulted in marked reductions in resting membrane potential, upstroke and duration of the action potential.
In the presence of the modified compared with normal PSS, buprenorphine reduced the action potential height and MRD of both sheep Purkinje fibres and rat papillary muscles to a greater extent, although its ability to prolong the action potential duration was attenuated.
The antiarrhythmic effects of buprenorphine observed in vivo may be explained by its direct cardiac electrophysiological effects. Buprenorphine might be useful in relieving pain and in reducing the severity of arrhythmias in the early stages of acute myocardial infarction.
Effects of endogenous and synthetic prostanoids, the thromboxane A2 receptor agonist U‐46619 and arachidonic acid on [3H]‐noradrenaline release and vascular tone in rat isolated kidney
Authors: Rump L.C. , Schollmeyer P. 
Published: July 2012

Rat kidneys were perfused with Krebs‐Henseleit solution and the perfusion pressure was monitored. After incubation with [3H]‐noradrenaline the renal nerves were stimulated. The stimulation‐induced (S‐I) outflow of radioactivity was taken as an index of noradrenaline release. The effect of prostaglandins on perfusion pressure, pressor responses to renal nerve stimulation (RNS) and S‐I outflow of radioactivity was assessed.
Prostaglandin E2 (PGE2, 0.06 and 0.6 μm), PGF2α (0.6 μm), PGI2 (0.6 and 3 μm) and iloprost (0.6 μm) increased perfusion pressure and enhanced pressor responses to RNS. These facilitatory effects of the prostaglandins were not a result of an enhanced transmitter release. In contrast, PGE2 dose‐dependently inhibited, whereas the other prostaglandins failed to modulate S‐I outflow of radioactivity. PGE2 (0.6 μm) also enhanced pressor responses to exogenous noradrenaline.
Arachidonic acid (1 μm) increased perfusion pressure and enhanced pressor responses to RNS. These effects were abolished in the presence of indomethacin (10 μm) suggesting that local production of prostaglandins from exogenous arachidonic acid was responsible for this facilitation. However, arachidonic acid (1 μm) did not modulate S‐I outflow of radioactivity. Arachidonic acid (10 μm), despite causing a marked increase in perfusion pressure, failed to alter pressor responses to RNS and only slightly inhibited S‐I outflow of radioactivity.
The thromboxane A2 (TxA2) receptor agonist U‐46619 (0.1 μm) increased vascular tone and enhanced pressor responses to RNS. These effects were blocked by the newly developed selective TxA2 receptor antagonist, daltroban (BM 13505; 3 μm), suggesting that these facilitatory effects of U‐46619 were due to activation of TxA2 receptors. However, U‐46619 failed to alter the S‐I outflow of radioactivity from rat isolated kidney.
The α1‐adrenoceptor agonist methoxamine (1 μm) also increased perfusion pressure and enhanced pressor responses to RNS without affecting the S‐I outflow of radioactivity in the presence of the prostaglandin synthesis inhibitor indomethacin (10 μm).
The results suggest that PGE2 modulates noradrenaline release through an inhibitory prejunctional receptor mechanism. There is no evidence for prejunctional PGF2α, PGI2 or TxA2 receptors in the rat isolated kidney. All prostaglandins increased vascular tone in the rat isolated kidney and this alone may provide a condition for enhanced pressor responses to RNS since methoxamine also enhanced pressor responses to RNS without affecting S‐I outflow of radioactivity. It is probable that postjunctionally active PGF2α and PGI2 is formed locally from exogenous arachidonic acid, but not enough prejunctionally active PGE2 is synthesized to modulate renal transmitter release.
Mode of antinociceptive action of flupirtine in the rat
Authors: Szelenyi I. , Nickel B. , Borbe H.O. , Brune K. 
Published: July 2012

Flupirtine is a novel, centrally acting, non‐opioid analgesic agent. The present investigation was undertaken to ascertain which neuronal systems might be responsible for its antinociceptive effect in rodents. The antinociceptive responses to the test compounds were examined in the tail‐flick test.
The selective destruction of noradrenergic pathways by 6‐hydroxydopamine considerably reduced the flupirtine‐induced inhibition of nociceptive responses but not the clonidine‐induced antinociception which was significantly enhanced. Depletion of spinal 5‐hydroxytryptaminergic pathways by pretreatment with 5,7‐dihydroxytryptamine failed to affect the action of flupirtine and clonidine.
The depletion of neurotransmitters by reserpine totally abolished the antinociceptive action of flupirtine. By contrast, clonidine‐induced inhibition of nociceptive responses remained unchanged.
Inhibition of the synthesis of noradrenaline by α‐methyl‐L‐p‐tyrosine attenuated the antinociception induced by flupirtine. In contrast, inhibition of the synthesis of 5‐hydroxytryptamine by (±)−6‐fluorotryptophan did not influence the antinociceptive activity of flupirtine.
Inhibition of noradrenaline uptake by imipramine led to a significant augmentation of flupirtine‐induced antinociception.
Selective antagonists at α‐adrenoceptors significantly decreased the antinociceptive action of flupirtine. Antinociception induced by clonidine was significantly diminished by idazoxan but not by prazosin.
The 5‐hydroxytryptamine (5‐HT) antagonist, ketanserin diminished the antinociceptive activity of flupirtine, probably due to its additional α1‐adrenoceptor antagonist activity. The antinociceptive effect of clonidine was not influenced by ketanserin.
Cholinoceptor antagonists such as mecamylamine and pirenzepine did not alter the antinociceptive action of flupirtine. Flupirtine‐induced antinociception also remained unchanged after pretreatment with haloperidol.
Flupirtine has no pharmacologically relevant affinity for α1‐, α2‐adrenoceptors, 5‐HT1‐ and 5‐HT2‐receptors as shown in direct binding studies.
The present results indicate that the antinociceptive action induced by flupirtine depends on the descending noradrenergic pain‐modulating system.
Actions of constrictor (NPY and endothelin) and dilator (substance P, CGRP and VIP) peptides on pig splenic and human skeletal muscle arteries: involvement of the endothelium
Authors: Pernow John 
Published: July 2012

The effects of various vasoactive peptides and the involvement of the endothelium in these effects were studied on small human skeletal muscle arteries (SMA) and pig splenic arteries (SA) in vitro.
Under control conditions, neuropeptide Y (NPY) caused potent and strong contractions of both arteries. The maximal effect of NPY 500 nM was similar to that of phenylephrine and noradrenaline (10 μm). Endothelin was approximately 10 fold more potent than NPY in contracting SA, and the maximal response to endothelin 50 nM was 130% of that evoked by phenylephrine.
After removal of the endothelium (by rubbing the inner surface of the arteries) neither the maximal effect nor the EC50 value of NPY on SMA and SA or those of endothelin on SA were changed from control conditions.
The substance P (SP)‐induced relaxation of precontracted SMA and SA during control conditions (80–90%) was abolished or greatly reduced after endothelium removal.
Under control conditions, calcitonin gene‐related peptide (CGRP) was about 10 times more potent than vasoactive intestinal polypeptide (VIP) in relaxing SMA. After endothelium removal the relaxation induced by CGRP on SMA and SA and that of VIP on SMA were not changed from control conditions.
It is concluded that, in the SMA and SA, the potent vasoconstrictor effects of NPY and endothelin are mediated by direct actions on the vascular smooth muscle and not via a release of an endothelium‐derived contracting factor. Relaxation induced by SP but not that of CGRP and VIP seems to be mediated via the endothelium.
Alterations in atrial reactivity in a strain of spontaneously diabetic rats
Authors: Durante William , Sunahara Fred A. , Sen Amar K. 
Published: July 2012

The present study examined the reactivity of atria from control and spontaneously diabetic rats to various adrenoceptor agonists and to adenosine.
Isoprenaline (1.5 nM‐1500 nm) produced concentration‐dependent increases in inotropy which were unchanged in diabetic atria. However, the sensitivity to isoprenaline‐induced changes in chronotropy was reduced in diabetic preparations.
In the presence of propranolol (2 μm), phenylephrine (0.2 μm‐100 μm) produced concentration‐dependent increases in both inotropy and chronotropy; however, atria from diabetic rats exhibited a much greater maximal response. The diabetic state did not alter the sensitivity to phenylephrine.
Adenosine (0.15 μm‐300 μm) produced concentration‐dependent decreases in both inotropy and chronotropy which were unchanged in diabetic atria.
Radioligand binding studies revealed that both α1‐and β‐adrenoceptor populations were substantially reduced in atria from diabetic rats. However, there was no change in receptor affinity for either adrenoceptor.
These results show that diabetes leads to an alteration in atrial reactivity to adrenoceptor stimulation. Future studies examining steps following hormone‐receptor coupling are required in order to characterize this defect.
Sodium salicylate facilitates calcium‐dependent release of transmitter at mouse neuromuscular junctions
Authors: Nishimura Masakazu , Awano Hideto , Yagasaki Osamu 
Published: July 2012

The effects of sodium salicylate on the frequency of miniature endplate potentials (m.e.p.ps) and on the quantal content of endplate potentials (e.p.ps) in mouse diaphragm muscles at 36°C and 24°C were studied by conventional microelectrode techniques.
At 36°C, salicylate (10 mm) elevated the frequency of m.e.p.ps in a manner which was insensitive to [Mg2+]o and independent of the presence of [Ca2+]o. Lowering the temperature to 24°C abolished the stimulating effect. 2,4‐Dinitrophenol (10 μm) had similar effects at 36°C and these disappeared at 24°C. All subsequent experiments were performed at 24°C.
Salicylate (10 mm) further increased the frequency (F) of m.e.p.ps stimulated by [Ca2+]o in a depolarizing solution. When [Ca2+]o was varied in the absence of salicylate, a linear relationship between ln(F) and ln([Ca2+]o) was obtained. Salicylate shifted this relationship to the left, with respect to the control, without altering the slope.
Salicylate (5 mm) also increased the quantal content (m) of e.p.ps in a solution that contained 5 mM Mg2+, in a concentration‐dependent fashion. As [Ca2+]o was varied in the absence of salicylate, a linear relationship between ln(m) and ln([Ca2+]o) was observed. Salicylate shifted this linear relationship to the left, with respect to the control, without altering the slope. Doubling the concentration of [Mg2+]o antagonized this effect of salicylate on the quantal content of e.p.ps.
These results indicate that salicylate enhances the effect of changing [Ca2+]o. Salicylate probably facilitates the entry of Ca2+ into the nerve terminal or sensitizes the process that is regulated by Ca2+, thereby stimulating the release of transmitter. Surface negative charges may have an important role in the effect of [Ca2+]o.
Action of atrial natriuretic peptide (ANP) on dog cerebral arteries: evidence that neurogenic relaxation is not mediated by release of ANP
Authors: Okamura Tomio , Inoue Seiji , Toda Noboru 
Published: July 2012

Atrial natriuretic peptide (ANP) (10−9 to 10−8m) produced a concentration‐related relaxation in helical strips of dog cerebral arteries partially contracted with prostaglandin F2α. The relaxation was not affected by treatment with ouabain, quinidine, oxyhaemoglobin, methylene blue, or removal of endothelium.
Relaxations induced by nicotine or transmural electrical stimulation were not reduced in arteries in which tachyphylaxis to ANP had developed.
In arteries exposed to Ca2+‐free media under severe hypoxia, contractions due to prostaglandin F2α and Ca2+ were attenuated by treatment with ANP, whereas the reoxygenation‐induced contraction was unaffected.
The results suggest that ANP does not mediate neurogenic relaxation of dog cerebral arteries. The ANP‐induced relaxation is not associated with activation of the sodium pump but is due to an inhibitory action on the release and influx of Ca2+, probably as a result of stimulation of guanylate cyclase.
Apparent affinity of 1,3‐dipropyl‐8‐cyclopentylxanthine for adenosine A1 and A2 receptors in isolated tissues from guinea‐pigs
Authors: Collis M.G. , Stoggall S.M. , Martin F.M. 
Published: July 2012

The classification of adenosine receptor subtypes (A1 and A2) in intact tissues has been based on the order of agonist potency. In this study the apparent affinity of 1,3‐dipropyl‐8‐cyclopentylxanthine (CPX), an antagonist which has been reported to be A1 selective, and the nonselective antagonist 1,3‐dimethyl‐8‐phenylxanthine (8PT) has been evaluated on isolated tissues from the guinea‐pig.
The isolated tissues used were atria (bradycardic response, proposed A1 sub‐type), aorta and trachea (relaxant response, proposed A2 sub‐type).
Both the xanthines antagonized responses to adenosine in the three tissues but had little or no effect on responses to carbachol (atria), sodium nitrite (aorta) or isoprenaline (trachea).
pA2 values for 8PT were similar on the three tissues (6.3–6.7), however, the pA2 value for CPX on the atria (7.9‐8.4) was greater than that on the aorta (6.6) or trachea (6.6).
These results support the suggestion that the adenosine receptors which mediate bradycardia in the atrium are of the A1 sub‐type and that those which mediate relaxation in the aorta and trachea are of the A2 type.
Effects of N‐ethylmaleimide on 5‐hydroxytryptamine transport and sodium content in rabbit platelets
Authors: Wölfel R. , Halbrügge T. , Graefe K.‐H. 
Published: July 2012

The present study analysed the mechanism underlying the inhibitory action of N‐ethylmaleimide (NEm) on the 5‐hydroxytryptamine (5‐HT) uptake by blood platelets.
Rabbit platelets suspended in protein‐free buffer were first preincubated for 45 min in the absence and presence of NEM (20 to 160 μm) or ouabain (0.5‐2.0 μm) and then either analysed for their Na+ and K+ content or incubated (15 s) with various concentrations of [3H]‐5‐HT (0.13‐4.03 μm) to determine Km and Vmax for 5‐HT uptake.
Both NEM and ouabain produced concentration‐dependent decreases in Vmax with IC50 values of 52 and 0.58 μm, respectively. Neither drug changed Km significantly.
Both NEM and ouabain increased the Na+ and decreased the K+ content of platelets in a concentration‐dependent manner.
There was a linear correlation between Vmax (expressed in % of control) and the reciprocal cellular Na+ content, with the results for both drugs falling onto one and the same regression line (r = 0.992; n = 8). This regression showed that an increase in Na+ content by 69% sufficed to reduce Vmax by 50%.
At concentrations that reduced 5‐HT uptake by about 60%, neither NEM nor ouabain altered the potency of imipramine for inhibition of 5‐HT uptake.
Hence, NEM inhibits 5‐HT transport by inhibiting the Na+/K+‐ATPase and not by a direct interaction with the 5‐HT carrier. The consequential increase in the intracellular Na+ concentration reduces the transmembrane Na+ gradient and, therefore, hinders 5‐HT inward transport. This action of the drug does not affect the ability of the carrier to bind 5‐HT or imipramine.
A comparison of basal and agonist‐stimulated release of endothelium‐derived relaxing factor from different arteries
Authors: Christie M.I. , Griffith T.M. , Lewis M.J. 
Published: July 2012

The release of endothelium‐derived relaxing factor (EDRF) from rabbit aorta and pig coronary artery vessels in response to acetylcholine (ACh), substance P (SP) and the calcium ionophore A23187 has been studied by means of a bioassay cascade system.
A technique is described which allows the quantification of EDRF release rates from vessels of different sizes, perfused at different flow rates and with different donor‐recipient transient times.
Rabbit aorta and pig coronary arteries, perfused at flow rates which equalise endothelial shear stress, released EDRF at a similar basal rate.
In response to ACh, rabbit aortic endothelium released EDRF at a significantly greater maximum rate than pig coronary artery endothelium.
In response to SP, both endothelium types released EDRF; SP was a significantly more potent agonist in pig coronary artery than in rabbit aorta, but maximum SP‐induced EDRF release from rabbit aorta was twice that of pig coronary artery.
These data indicate that different endothelium types can release EDRF at widely different rates, according to the agonist used, and that the previously obtained lack of relaxant response to ACh in pig coronary artery was due to a lack of EDRF release rather than concomitant smooth muscle constriction.
Prejunctional modulatory action of neuropeptide Y on peripheral terminals of capsaicin‐sensitive sensory nerves
Authors: Giuliani Sandro , Maggi Carlo Alberto , Meli Alberto 
Published: July 2012

We have determined the effect of neuropeptide Y (NPY) on motor responses produced by activation of capsaicin‐sensitive primary afferents in the guinea‐pig isolated left atria (reserpine‐pretreatment, atropine in the bath) and bronchi (atropine and indomethacin in the bath) using capsaicin itself and electrical field stimulation as stimuli.
In both preparations, NPY inhibited or suppressed the response produced by electrical field stimulation while leaving the response to a submaximal concentration of capsaicin unaffected.
NPY had no effect on motor responses produced by a submaximal concentration of calcitonin gene‐related peptide (atria) or neurokinin A (bronchi), the putative endogenous mediators of the responses produced by activation of the ‘efferent’ function of sensory fibres in these preparations.
We conclude that NPY exerts a prejunctional inhibitory action on transmitter release from peripheral endings of capsaicin‐sensitive nerves. Failure of NPY to modulate responses activated by capsaicin provides further evidence for the existence of two independent modes of activation of the ‘efferent’ function of capsaicin‐sensitive sensory nerves.
Regulation of the substance P‐induced contraction via the release of acetylcholine and γ‐aminobutyric acid in the guinea‐pig urinary bladder
Authors: Shirakawa Junji , Nakanishi Tateo , Taniyama Kohtaro , Kamidono Sadao , Tanaka Chikako 
Published: July 2012

The action of substance P (SP) on the release of γ‐aminobutyric acid (GABA) and acetylcholine (ACh) and on contraction were studied in strips of the guinea‐pig urinary bladder. Substance P induced a dose‐dependent contraction of strips of guinea‐pig urinary bladder (EC50 =1.2 × 10−9m). This contraction was not altered by tetrodotoxin, but with a dose of 10−9m and less, there was a complete inhibition by 10−6m atropine. Contractions initiated by 3 × 10−9m SP or more were partly inhibited by atropine. The EC50 value of substance P in the presence of atropine was 7.0 × 10−9m.
Substance P induced a Ca2+‐dependent and tetrodotoxin‐resistant release of [3H]‐acetylcholine (ACh) from strips of urinary bladder preloaded with [3H]‐choline (EC50 = 4.9 × 10−10m), and this release was antagonized by [D‐Pro2,D‐Trp7′9]substance P.
Bicuculline increased the substance P‐induced contraction and the release of [3H]‐ACh from the strips.
Substance P induced a Ca2+‐dependent and tetrodotoxin‐sensitive release of [3H]‐γ‐aminobutyric acid (GABA) from strips preloaded with [3H]‐GABA (EC50 = 2.6 × 10−9m), and this release was antagonized by [D‐Pro2,D‐Trp7′9]substance P.
Therefore, substance P appears to exert excitatory effects on the contractility of urinary bladder predominantly by stimulating its own receptor located on the cholinergic nerve terminals. GABA released by substance P inhibits stimulation of the cholinergic neurone. However, the direct action of substance P on the cholinergic neurone is more potent that the indirect action via GABA release.
A comparison of haemoglobin and erythrocytes as inhibitors of smooth muscle relaxation by the NANC transmitter in the BRP and rat anococcygeus and by EDRF in the rabbit aortic strip
Authors: Gillespie John S. , Sheng Hong 
Published: July 2012

The inhibitory effect of erythrocyte suspensions and haemoglobin solutions on the response of the bovine retractor penis muscle (BRP) and the rat anococcygeus to field stimulation of their non‐adrenergic non‐cholinergic (NANC) nerves has been compared. Haemoglobin 3 μm greatly reduced the relaxant response in both tissues whereas a haemoglobin‐equivalent suspension of erythrocytes was without effect.
A similar comparison of erythrocytes and haemoglobin on the response of the rabbit aortic strip to EDRF liberated by acetylcholine (ACh) showed that both reduced EDRF‐mediated relaxation, though haemoglobin was significantly more effective.
These results suggest that the NANC transmitter may not be as freely diffusible through the erythrocyte membrane as EDRF and may therefore not be nitric oxide.