bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superoxide anions enhance platelet adhesion and aggregation
Authors: Salvemini Daniela , de Nucci Gilberto , Sneddon John M. , Vane John R. 
Published: July 2012

Superoxide dismutase (SOD, 60 u ml−1) or ferricytochrome c (70 μm) significantly inhibited thrombin‐stimulated platelet adhesion to gelatin‐coated plastic, whereas catalase (1000 u ml−1) or mannitol (1 mm) had no effect.
The platelet aggregation induced by low concentrations of thrombin (causing less than 45% maximal change in light transmission) was inhibited by SOD. Catalase or mannitol had no effect on platelet aggregation.
Pyrogallol (an O2− generator) enhanced both platelet adhesion to gelatin‐coated plastic and platelet aggregation induced by thrombin; this enhancement was neutralized by SOD.
These results indicate that O2− increase both platelet adhesion and aggregation, whereas other free radicals such as hydrogen peroxide or hydroxyl radicals are not involved.
Angiotensin neuromodulation of adrenergic and purinergic co‐transmission in the guinea‐pig vas deferens
Authors: Ellis James L. , Burnstock Geoffrey 
Published: July 2012

The effects of angiotensin II (AII) and angiotensin III (AIII) on the isolated vas deferens of the guinea‐pig were studied via three parameters: the overflow of adenosine 5′‐triphosphate (ATP) and tritiated noradrenaline (NA), the mechanical response to field stimulation and the mechanical response to exogenous NA and α,β‐methylene ATP (α,β‐mATP).
At 2Hz, All enhanced the overflow of ATP and NA, whereas at 20 Hz, All enhanced the overflow of NA but was without significant effect on ATP overflow. AIII, at 2 Hz, inhibited the overflow of ATP, but enhanced NA overflow, whereas at 20 Hz ATP overflow was unaffected, but NA overflow was still enhanced.
At 2 Hz, AII enhanced both phases of the response to field stimulation and at 20 Hz the overall response. AIII at 2 Hz enhanced the adrenergic response, but was without effect on the purinergic response to field stimulation. At 20 Hz, AIII was without effect on the overall response.
AII enhanced responses to exogenous NA and α,β‐mATP, whereas AIII was without effect.
These results provide evidence that both ATP and NA release are capable of being modulated by angiotensins. Furthermor, modulation of ATP release is frequency‐dependent, whereas [3H]‐NA release is not. These results raise questions about the mechanisms of storage and release of the sympathetic co‐transmitters NA and ATP; they also show that angiotensin receptors in the guinea‐pig vas deferens are not a homogeneous population.
Pronounced cholinergic but only moderate purinergic effects in isolated atrial and ventricular heart muscle from cats
Authors: Kemmer Michael , Jakob Helga , Nawrath Hermann 
Published: July 2012

The effects of cholinergic and purinergic stimulation on action potential, force of contraction and 86Rb efflux were investigated in cat atrial and/or ventricular heart muscle.
Acetylcholine and carbachol exerted a concentration‐dependent negative inotropic effect in cat atrial heart muscle. Carbachol 10 μmol l−1 completely abolished the force of contraction and increased the rate constant of 86Rb efflux 2–3 fold, whereas the action potential duration was shortened to about 1/10 of its length under control conditions.
The effects of acetylcholine and carbachol in cat atrial heart muscle were mimicked, qualitatively, by adenosine and its analogues 5′‐(N‐ethyl)‐carboxamido‐adenosine (NECA) and (−)‐N6‐(R‐phenyl‐isopropyl)‐adenosine (R‐PIA). Maximal purinergic effects, however, amounted to about 15–50% in comparison to those of cholinergic stimulation.
In cat ventricular heart muscle, cholinergic or purinergic stimulation had no significant effects on the force of contraction in the absence of a cyclic AMP‐dependent positive inotropic effect. Carbachol antagonized the positive inotropic effect elicited by either 3‐isobutyl‐1‐methylxanthine, isoprenaline or cyclic 8‐(4‐chlorphenylthio)adenosine‐3′:5′‐monophosphate; NECA and R‐PIA were less effective. The inhibition by carbachol of the effects of isoprenaline was not related to a change in the rate constant of 86Rb efflux.
It is concluded that the effects of cholinoceptor and purinoceptor agonists in the cat heart involve a change in the potassium conductance in the atrium, whereas the effects in the ventricle may be related to changes of intracellular cyclic AMP levels. It seems reasonable to assume that, in comparison to cholinergic stimulation, a low density of purinoceptors in the cat heart is responsible for the relatively weak effects of adenosine agonists in this species.
The effects of alterations in electrogenic Na+/K+‐pumping in guinea‐pig isolated trachealis: their modulation by the epithelium
Authors: Raeburn David , Fedan Jeffrey S. 
Published: July 2012

An examination was made of the effect of epithelium removal on mechanical responses of guinea‐pig isolated tracheal strips after inhibition or activation of electrogenic Na+/K+‐pumping.
The Na+/K+‐pump inhibitor ouabain (0.1–10 μm) evoked concentration‐dependent contractions which were potentiated by epithelium removal.
K+‐free solution, which inhibits Na+/K+‐pumping, produced a slow, sustained relaxation in intact preparations. In epithelium‐free preparations the relaxation was transient and of lesser magnitude.
The addition of K+ (10 or 30 mm), which activates Na+/K+‐pumping, to preparations bathed in K+‐free solution caused a relaxation of preparations under spontaneous tone or contracted with methacholine; the magnitude and duration of relaxation was greater in the epithelium‐free preparations. Ouabain (0.1 μm) attenuated the relaxation to K+ in intact preparations and converted the response of epithelium‐free preparations to a contraction. In the presence of a higher concentration of ouabain (1 μm), intact preparations contracted in response to K+.
In normal K+ solution, ouabain (0.1 μm) increased the sensitivity of intact preparations to methacholine but reduced their sensitivity to K+. Ouabain was without these effects in epithelium‐free preparations.
Thus, responses of intact preparations to perturbations which affect electrogenic Na+/K+‐pumping in trachealis are influenced by an epithelium‐derived factor. The production of the factor may be linked to an epithelial Na+/K+‐pump, or the factor may modulate the activity of an electrogenic Na+/K+‐pump in the muscle.
Endothelin‐induced contractions of tracheal smooth muscle and identification of specific endothelin binding sites in the trachea of the rat
Authors: Turner N.C. , Power R.F. , Polak J.M. , Bloom S.R. , Dollery C.T. 
Published: July 2012

The presence of specific binding sites and the contractile activity of the novel peptide, endothelin have been investigated in rat trachea.
Endothelin (10−8–10−5m) induced long‐lasting contraction of rat tracheal rings superfused with Krebs solution (EC50 5.4 × 10−6m). Contractions of the tissue to 10−6m endothelin were attenuated in Ca2+‐free medium containing 0.1 mM EGTA but unaffected by nicardipine (10−7m).
After equilibration in Ca2+‐free medium (without EGTA) a return to normal Ca2+ concentrations (2.5 mm), 30 min or 60 min following endothelin (10−6m), produced a sustained contraction of the tissue.
Specific binding sites for endothelin were identified on rat tracheal smooth muscle (KD 1.34 × 10−10m, maximal binding 1.2 fmol mm−2). Specific binding sites were also identified on nerve trunks. Endothelin binding was unaffected by co‐incubation with nicardipine (10−7m) or verapamil (10−7m).
The discrepancy between the apparent KD for endothelin binding and the EC50 for endothelin‐induced contraction suggests that the endothelin binding sites identified in this study may not be associated with the receptors mediating contraction.
These results indicate that endothelin binding sites are present on tracheal smooth muscle. The mechanism of endothelin‐induced contraction, whilst being dependent on extracellular calcium, does not appear to involve binding to the dihydropyridine‐ or verapamil‐sensitive sites on the voltage‐dependent Ca2+ channel. Its long duration of action may be associated with a sustained increase in Ca2+ permeability.
Possible therapeutic effect of naftidrofuryl oxalate on brain energy metabolism after microsphere‐induced cerebral embolism
Authors: Miyake Keiko , Tanonaka Kouichi , Minematsu Reiko , Inoue Kiyoshi , Takeo Satoshi 
Published: July 2012

The present study was designed to determine whether naftidrofuryl oxalate exerts a possible therapeutic effect on brain energy metabolism impaired by microsphere‐induced cerebral embolism in vitro.
Injection of microspheres into the right carotid canal resulted in a decrease in tissue high‐energy phosphates both in the right and left hemispheres, and an increase in tissue lactate in the right hemisphere, on the 3rd and the 5th day after the embolism. The embolism also induced a marked reduction in mitochondrial oxidative phosphorylation ability and succinate dehydrogenase activity. The results suggest that severe ischaemia was induced in the brain by the microsphere administration.
Treatment of microsphere‐injected rats with naftidrofuryl oxalate (15 mg kg−1) for 3 or 5 days elicited a significant recovery of tissue high‐energy phosphate and lactate levels. The recovery was associated with a significant restoration of mitochondrial succinate dehydrogenase activity on the both days and of mitochondrial oxidative phosphorylation rate on the 5th day.
The results suggest that naftidrofuryl oxalate is beneficial in the recovery of cerebral energy metabolism impaired by microsphere‐induced cerebral ischaemia, presumably through a mechanism involving its direct effect on the cerebral mitochondrial enzyme activities.
Arterial chemoreceptor involvement in salicylate‐induced hyperventilation in rats
Authors: McQueen D.S. , Ritchie Isobel M. , Birrell G.J. 
Published: July 2012

The extent to which peripheral arterial chemoreceptors are involved in the respiratory stimulant action of salicylates has been investigated in rats.
Injection of sodium salicylate (200 mg kg−1, single dose i.v.) caused a rapid transient hyperventilation that was not obtained when the carotid chemoreceptors were denervated by section of the carotid sinus nerves. A delayed (10 min) increase in respiration occurred regardless of whether or not the carotid nerves were sectioned.
Intravenous infusions of sodium salicylate (0.5 or 4 mg kg−1 min−1) caused hyperventilation in barbiturate‐anaesthetized rats. The threshold dose for respiratory stimulation was significantly lower when the carotid sinus nerves were intact than when they were bilaterally sectioned, and the same pattern was observed following intravenous injections of sodium salicylate (cumulative doses) in anaesthetized and conscious rats.
Bilateral sectioning of the vagosympathetic nerve trunks did not significantly affect hyperventilation evoked by salicylate, suggesting that this response does not involve actions of salicylate on sensory receptors innervated by these nerves.
Administration of salicylate close‐arterial to a carotid body, by local perfusion or crossperfusion of a carotid sinus, led to an increase in respiration when the ipsilateral carotid nerve was intact, but not when it was sectioned.
Neuropharmacological studies on anaesthetized rats showed that chemosensory discharge, recorded from a sectioned carotid nerve, increased in response to salicylate injections with a similar dose‐response pattern to the hyperventilation. Salicylate had no effect on baroreceptor discharge.
We conclude from our experiments that arterial chemoreceptors do contribute to salicylate‐induced hyperventilation, and are almost exclusively responsible for the initial phase of the response in rats. Later increases in breathing are independent of reflexes from arterial chemoreceptors and result from actions at other sites, including the CNS. The therapeutic implications of our results are discussed.
Cyclosporin therapy in vivo attenuates the response to vasodilators in the isolated perfused kidney of the rabbit
Authors: Cairns Hugh S. , Fairbanks Lynette D. , Westwick John , Neild Guy H. 
Published: July 2012

The endothelium releases a number of vasoactive compounds, including the vasodilator prostaglandins, prostacyclin (PGI2) and prostaglandin E2 (PGE2) and endothelium‐derived relaxing factor (EDRF), which play an important role in the regulation of vascular tone in the microcirculation. Nephrotoxicity is the major complication of cyclosporin (CS) therapy and is related to an increase in intrarenal vascular tone. Endothelial cell generation of PGI2 is inhibited by CS although this cannot fully explain the changes in vascular tone observed. We have investigated the possibility that EDRF‐dependent vasodilatation is also affected by CS therapy in vivo.
CS nephrotoxicity was induced in rabbits with CS (15 mg kg−1 per day s.c. for 20 days (n = 6)); 6 rabbits were given CS vehicle (Veh) and 9 animals were studied without any treatment. Creatinine clearance fell significantly during treatment in the CS‐treated rabbits (11.78 ± 1.5 ml min−1, mean ± s.e.mean, to 7.79 ± 1.2 after 20 days treatment) but did not change in the vehicle‐treated animals.
The responses to the endothelium‐dependent (acetylcholine (ACh)) and endothelium‐independent (nitroprusside (NP) and PGI2) vasodilators were assessed in indomethacin‐treated isolated perfused kidneys (IPKs) from untreated, CS‐ and Veh‐treated animals. Vascular tone was induced with a constant infusion of noradrenaline 150 nM and the perfusion rate adjusted to produce a perfusion pressure of 90 mmHg. Perfusate flow rate (22.3 ± 4.6 vs 20.4 ± 3.1 ml min−1) and glomerular filtration rate (2.04 ± 0.37 vs 1.88 ± 0.16 nl min−1) did not differ between IPKs from CS‐ and Veh‐treated animals.
The vasodilator response to ACh was reduced in the kidneys from CS‐treated animals compared with those from untreated and Veh‐treated animals (mean reduction 35.3 ± 2.3% compared with Veh) as were the responses to both NP (42.8 ± 3.6%) and PGI2 (27.7 ± 7.4%).
This suggests that CS nephrotoxicity is not mediated via an effect on endothelium‐dependent responses and that it is more likely that CS has a direct effect on vascular smooth muscle.
Modulation of the vasodepressor actions of acetylcholine, bradykinin, substance P and endothelin in the rat by a specific inhibitor of nitric oxide formation
Authors: Whittle B.J.R. , Lopez‐Belmonte J. , Rees D.D. 
Published: July 2012

The effects of the specific inhibitor of nitric oxide (NO) formation, NG‐monomethyl‐L‐arginine (L‐NMMA), on resting systemic arterial blood pressure (BP) and on the actions of both endothelium‐dependent and endothelium‐independent vasodilators were investigated in the anaesthetized, normotensive rat.
Intravenous administration of L‐NMMA (12.5–50 mg kg−1; 47–188 μmol kg−1) but not its enantiomer, D‐NMMA, induced a dose‐related increase in BP, which was reversed by the intravenous administration of L‐arginine (150–600 μmol kg−1), but not D‐arginine.
The vasodepressor responses to intravenous administration of the endothelium‐dependent vasodilators, acetylcholine, bradykinin and substance P were significantly inhibited by L‐NMMA (94 and 188 μmol kg−1 i.v.), but not by D‐NMMA.
The inhibition by L‐NMMA of these vasodepressor responses was reversed by administration of L‐arginine, but not D‐arginine.
Endothelin (ET‐1) induced dose‐related vasodepressor responses following bolus intravenous administration, which were significantly inhibited by L‐NMMA but not by D‐NMMA. This inhibition was reversed by administration of L‐arginine.
The vasodepressor effects of the endothelium‐independent vasodilators, glyceryl trinitrate or prostacyclin, were not significantly inhibited by L‐NMMA.
These findings with L‐NMMA suggest that resting blood pressure in the rat is modulated by endogenous NO biosynthesis and that endothelium‐dependent vasodilators act through the formation of endogenous NO to exert their actions in vivo.
Effect of cromakalim on bronchoconstriction evoked by cholinergic nerve stimulation in guinea‐pig isolated trachea
Authors: McCaig Dorothy J. , De Jonckheere B. 
Published: July 2012

Cromakalim reduced intraluminal pressure in the guinea‐pig isolated, innervated trachea.
Preganglionic stimulation of the cervical vagus nerve elicited a frequency‐dependent increase in intraluminal pressure. Cromakalim attenuated responses to vagal stimulation in a concentration‐dependent manner at all frequencies tested.
Field stimulation caused a frequency‐dependent increase in intraluminal pressure mediated by muscarinic cholinoceptors. Cromakalim did not affect the amplitude of responses at any frequency of stimulation, even at high concentrations.
Acetylcholine, added to the Krebs solution bathing the adventitial surface of the trachea, evoked a concentration‐dependent increase in intraluminal pressure. The concentration‐effect curve for acetylcholine was unaltered in the presence of cromakalim.
It is concluded that cromakalim modulates cholinergic neuroeffector transmission in the trachea chiefly by a prejunctional mechanism. However, cromakalim probably does not interfere with acetylcholine release from postganglionic cholinergic neurones.
The cholinergic pharmacology of tetrahydroaminoacridine in vivo and in vitro
Authors: Hunter A.J. , Murray T.K. , Jones J.A. , Cross A.J. , Green A.R. 
Published: July 2012

The effect of tetrahydroaminoacridine (THA) on cholinergically mediated behaviour in the rat and mouse has been investigated. In addition the actions of this compound on cholinesterase activity and on muscarinic and nicotinic receptors has also been examined.
Administration of THA (5–20 mg kg−1, i.p.) produced a dose‐dependent increase in tremor, hypothermia and salivation in both rats and mice. A similar profile of activity was seen following physostigmine (0.1‐0.6 mg kg−1) administration.
THA was approximately fifty fold less potent than physostigmine in inducing behavioural change but its effects persisted for over twice as long as those of physostigmine. For example THA‐induced hypothermia was still present at 4 h in the mouse and 8 h in the rat.
In vitro THA was a potent non‐competitive inhibitor of rat brain cholinesterase (IC50: 57 + 6 nM) and bovine erythrocyte acetylcholinesterase (IC50: 50 + 10 nM) but was a more potent inhibitor of horse serum butyrylcholinesterase (IC50: 7.2 + 1.4 nM).
Radioligand binding studies indicated that THA binds non‐selectively but with moderate potency to both M1 (Ki: 600 nM) and M2 (Ki: 880 nM) muscarinic receptors. THA also interacted with the allosteric site present on cardiac M2 receptors.
It is concluded that THA is a reversible non‐competitive inhibitor of cholinesterase with a long half life (compared with physostigmine). It also may antagonize muscarinic receptors at high doses. The long half life may account for its reported efficacy in the treatment of Alzheimer's disease.
Effects of yohimbine on submaxillary salivation in dogs
Authors: Montastruc Paul , Berlan Michel , Montastruc Jean‐Louis 
Published: July 2012

The effects of yohimbine (0.5 mg kg−1 i.v.) on both resting and parasympathetic and sympathetic stimulation‐induced submaxillary salivary responses were investigated in the anaesthetized dog.
Salivary secretion was increased significantly for a period of 45 min following an injection of yohimbine.
Sectioning of the chorda tympani (but not the cervical sympathetic) nerve abolished the yohimbine‐induced increase in resting salivary secretion and potentiated that elicited by electrical stimulation of the chorda tympani nerve.
These results show that yohimbine increases submaxillary secretion by inhibition of presynaptic α2‐adrenoceptors located on the chorda tympani, which inhibit cholinergic transmission.
The mechanism of amphetamine‐induced inhibition of rat substantia nigra compacta neurones investigated with intracellular recording in vitro
Authors: Mercuri Nicola B. , Calabresi Paolo , Bernardi Giorgio 
Published: July 2012

The effects of (+)‐amphetamine (1–300 μm) applied by superfusion, on substantia nigra zona compacta neurones were studied in slices of the rat mesencephalon with intracellular recording techniques (current and voltage clamp mode).
Amphetamine inhibited the action potential discharge, hyperpolarized the cells and increased the membrane conductance. Under voltage clamp it produced an outward current.
The amphetamine outward current reversed at potentials negative to −100 mV (2.5 mM extracellular potassium) and was reduced by barium, (1 mM) suggesting an increased potassium conductance.
In slices treated with tetrodotoxin and calcium‐free solution and added cobalt, amphetamine was still effective.
(−)‐Sulpiride, (1 μm) a D2 antagonist, blocked the effects of both amphetamine and dopamine.
In slices treated for more than 3 h with 30 μm α‐methyl‐DL‐tyrosine, an agent known to block the synthesis of dopamine, the action of amphetamine was attenuated, while dopamine was still effective.
Responses to applied dopamine were potentiated by cocaine (10 μm) but unaffected by amphetamine (1–3 μm).
It is suggested that the inhibition of substantia nigra compacta neurones by amphetamine is mainly due to the release of endogenous dopamine.
Native and oxidized low‐density lipoproteins have different inhibitory effects on endothelium‐derived relaxing factor in the rabbit aorta
Authors: Jacobs Michael , Plane Frances , Bruckdorfer K. Richard 
Published: July 2012

The effect of native low‐density lipoproteins (LDL) and oxidized LDL (OXLDL) on the relaxations to endothelium‐derived relaxing factor (EDRF) in isolated, intact aortic rings of the rabbit were investigated.
Native LDL induced a concentration‐dependent reversible inhibition of the relaxations elicited by acetylcholine (ACh) or A23187, in rings pre‐contracted by noradrenaline (NA), adrenaline (Ad) and 5‐hydroxytryptamine (5‐HT), but not phenylephrine (PE), which was not influenced by indomethacin.
The inhibition was surmountable in the rings pre‐contracted with NA and Ad and only partially in those pre‐contracted with 5‐HT.
OXLDL induced an inhibition of the relaxations elicited by ACh and A23187 which was independent of the contractile agonist. The extent of inhibition and its reversibility varied with the LDL from individual donors, but was unaffected by indomethacin.
Native and oxidized LDL inhibited relaxations evoked by exogenous nitric oxide (NO) to the same extent. Higher concentrations of NO overcame the inhibition. The inhibition was independent of the contractile agonist and the preparation of LDL from individual donors.
Only OXLDL inhibited reversibly relaxations evoked by glyceryl trinitrate (GTN) and the inhibition was independent of the LDL preparation from individual donors.
This study demonstrates that native and OXLDL influence the response to EDRF in isolated aorta. We suggest that these lipoproteins may contribute to the attenuation of responses to EDRF found in isolated arteries from hypercholesterolaemic and atherosclerotic animals.