bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological analysis of established ventricular fibrillation
Authors: Carlisle Euan J.F. , Allen J. Desmond , Kernohan W. George , Leahey W. , Adgey A.A. Jennifer 
Published: July 2012

The effects of antiarrhythmic drugs on the power spectrum of established ventricular fibrillation induced by endocardial electrical stimulation, have been studied in greyhounds anaesthetized with sodium pentobarbitone (35 mg kg−1, i.v.).
In dogs receiving no drug, initial recording of ventricular fibrillation showed a dominant frequency of 9.9 ± 0.7 Hz (lead II) and 10.0 ± 0.6 Hz (endocardium). After 3.3 min the frequency had fallen to 4.0 ± 0.4 Hz in lead II, but remained high in the endocardium (10.7 ± 0.5 Hz).
Lignocaine significantly reduced the dominant frequency for fibrillation recorded from lead II at (0–80 s), and for endocardial fibrillation at (0–200 s).
Pretreatment with propranolol or bretylium had little effect on the time course of the dominant frequency of fibrillation in lead II or the endocardium.
Verapamil prevented the fall in frequency seen in lead II after 80s in the no drug group. A significantly higher frequency was maintained in both lead II (14.7 ± 0.9 Hz) and the endocardium (14.8 ± 0.9 Hz) for 3.3 min, compared with the no drug group (P < 0.01).
Activation of fast sodium channels may determine the rapid frequency of the initial stages of ventricular fibrillation. The rapid fall in dominant frequency in lead II after fibrillation for 80s can be prevented by calcium channel blockade and may be due to intracellular accumulation of calcium.
The action of diazoxide and minoxidil sulphate on rat blood vessels: a comparison with cromakalim
Authors: Newgreen D.T. , Bray K.M. , McHarg A.D. , Weston A.H. , Duty S. , Brown B.S. , Kay P.B. , Edwards G. , Longmore J. , Southerton J.S. 
Published: July 2012

The actions of diazoxide and minoxidil sulphate have been compared with those of cromakalim in rat aorta and portal vein.
Diazoxide and minoxidil sulphate hyperpolarized the rat portal vein in a similar manner to cromakalim.
Cromakalim, diazoxide and minoxidil sulphate increased 42K and 86Rb efflux from rat portal vein, although minoxidil sulphate had only a small effect on 86Rb efflux.
Cromakalim, diazoxide and minoxidil sulphate increased 42K efflux from rat aorta but only cromakalim and diazoxide increased 86Rb efflux from this tissue.
Glibenclamide inhibited the relaxant actions of cromakalim, diazoxide and minoxidil sulphate on rat aorta and the increase in 42K efflux produced by these agents in this tissue.
Diazoxide relaxed an 80 mm KCl‐induced contraction of rat aorta, whilst cromakalim and minoxidil sulphate were without effect.
Cromakalim, diazoxide and minoxidil sulphate had no effect on cyclic AMP or cyclic GMP concentrations in rat aorta.
It is concluded that diazoxide and minoxidil sulphate like cromakalim exhibit K+ channel opening properties in vascular smooth muscle. Diazoxide exerts an additional inhibitory action not related to the production of cyclic AMP or cyclic GMP. The action of minoxidil sulphate may be primarily located at a K+ channel which is relatively impermeable to 86Rb.
Co‐operation between interleukin‐1 and the fibrinolytic system in the degradation of collagen by articular chondrocytes
Authors: Cruwys S.C. , Davies D.E. , Pettipher E.R. 
Published: July 2012

The interaction between interleukin 1 (IL‐1) and the fibrinolytic system in the control of collagen degradation by rabbit chondrocytes has been investigated in a tissue‐culture system where cells are grown on a 14C‐labelled collagen matrix.
Culture of rabbit chondrocytes in the presence of human recombinant IL‐1β at a concentration of 57 pm for 48 h led to the presence of procollagenase but not active collagenase in the medium. The latent collagenase could be activated by incubation with an organomercurial, aminophenylmercuric acetate (APMA).
Addition of IL‐1β to chondrocytes grown on a 14C‐labelled collagen matrix did not increase the degradation of the matrix compared to control over a 48 h period. However, in the presence of plasmin (200 μg ml−1) or plasminogen (100 μg ml−1), IL‐1β (57 pm) caused almost complete degradation of the collagen matrix. Plasmin or plasminogen alone caused only slight degradation of the collagen matrix.
Tissue inhibitor of metalloproteinases (TIMP) or the selective metalloproteinase inhibitor, SC44463, inhibited the degradation induced by IL‐1β and plasminogen in a concentration‐related manner and at concentrations that were correlated with inhibition of collagenase.
When concentrations of IL‐1β which caused only minimal degradation of the matrix in the presence of plasminogen were combined with fibrin (1 μg ml−1), there was almost total degradation of the matrix by 48 h.
These results indicate there is a synergistic interaction between IL‐1 and the fibrinolytic system in the degradation of collagen by rabbit chondrocytes in culture.
Temperature‐dependence of desensitization induced by acetylcholine and histamine in guinea‐pig ileal longitudinal muscle
Authors: Horio Shuhei , Shima Masanori , Ueda Haruyasu , Ishida Yukio 
Published: July 2012

The effects of temperature on the time course of desensitization induced by acetylcholine and histamine, and on the recovery from desensitization were studied in the longitudinal muscle of the guinea‐pig ileum.
Self‐ and cross‐desensitization produced by acetylcholine (10−5m) occurred rapidly in the first 10 min of exposure to the agonist, with the same time course and the same degree of desensitization over the temperature range of 11°C to 31°C.
Self‐desensitization produced by histamine (10−5m) also occurred rapidly in the first 10 min of exposure to the agonist, and showed great temperature‐dependence, especially at 11°C and 21°C, but scarcely occurred at 6°C.
Cross‐desensitization produced by histamine developed gradually with time and showed a moderate temperature‐dependence between 11°C and 31°C, but scarcely occurred at 6°C.
The recovery processes from desensitization showed marked temperature‐dependence. Recovery was halted completely at 11°C.
These studies suggest that acetylcholine‐induced desensitization may be attributed to a single nonspecific mechanism. Histamine‐induced desensitization may be due to at least two mechanisms: it occurs in both a specific and non‐specific manner. Each of these desensitizations can be characterized by its unique temperature‐dependence.
Temporal changes in the calcium‐force relation during histamine‐induced contractions of strips of the coronary artery of the pig
Authors: Hirano Katsuya , Kanaide Hideo , Abe Shimako , Nakamura Motoomi 
Published: July 2012

We examined temporal changes in the relationship between cytosolic calcium concentrations ([Ca2+]i) and developed tension during histamine‐induced contractions of strips of the coronary artery of the pig, by making use of simultaneous measurements of fura‐2 fluorescence and force.
The relationship between [Ca2+]i and developed tension observed with cumulative applications of extracellular Ca2+ ([Ca2+]o), ranging from 0 mm to 10 mm, during 118 mm K+‐depolarization was similar to that observed in chemically skinned strips of the porcine coronary artery, as noted by other investigators. [Ca2+]i at 0 mm [Ca2+]o, at 50% of maximum, and at maximum tension development were 76 nm, 424 nm, and 3050 nm, respectively.
Cumulative applications of histamine induced dose‐dependent increases in [Ca2+]i and tension and the extent of tension for a given change in [Ca2+]i increased, i.e. greater effectiveness of [Ca2+]i‐tension relationship, than seen with K+‐depolarization.
When histamine 10−5 m was applied, [Ca2+]i abruptly rose and reached the first peak within several seconds. After a slight dip at 30 s, [Ca2+]i reached a second peak at 3 min, and then gradually declined. On the other hand, tension developed rapidly reached a maximum at 4 min, then gradually declined. The relation between [Ca2+]i and tension in the early, rising phase of contraction was similar to that obtained during depolarization. At the time of maximum tension development, the relation was greater than that observed during depolarization, which persisted in the phase of declining tension.
To examine the role of protein kinase C in the increased effectiveness of [Ca2+]i‐tension relation of histamine‐induced contractions, we used 1‐(5‐isoquinolinesulphonyl)‐2‐methylpiperazine (H‐7), as an inhibitor. Exposure of strips to H‐7, 10−5 m, reduced the effectiveness of [Ca2+]i‐tension relation toward the level observed during depolarization, while it had no effect on the [Ca2+]i‐tension relation in the early phase of contraction either in the presence or absence of extracellular Ca2+.
In intact smooth muscle of the coronary artery of the pig, the relationship between [Ca2+]i and developed tension varies during contraction. Histamine, a receptor‐mediated stimulus, induced a greater tension for a given change in [Ca2+]i during the steady state of contraction than did depolarization. The greater effectiveness of contraction, particularly in the later phase, seems to be mediated by activation of an H‐7‐sensitive mechanisms.
Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor
Authors: Colmers William F. , Klapstein Gloria J. , Fournier Alain , St‐Pierre Serge , Treherne Kerri A. 
Published: July 2012

The action of analogues and C‐terminal fragments of neuropeptide Y (NPY) was examined on excitatory synaptic transmission in area CA1 of the rat hippocampal slice in vitro, by use of intracellular and extracellular recordings, to determine by agonist profile the NPY receptor subtype mediating presynaptic inhibition.
Neither NPY, analogues nor fragments of NPY affected the passive or active properties of the postsynaptic CA1 pyramidal neurones, indicating their action is at a presynaptic site.
The full‐sequence analogues, peptide YY (PYY) and human NPY (hNPY), were equipotent with NPY at the presynaptic receptor, while desamido hNPY was without activity.
NPY2–36 was equipotent with NPY. Fragments as short as NPY13–36 were active, but gradually lost activity with decreasing length. NPY16–36 had no effect on extracellular field potentials, but still significantly inhibited excitatory postsynaptic potential amplitudes. Fragments shorter than NPY16–36 had no measurable effect on synaptic transmission.
The presynaptic NPY receptor in hippocampal CA1 therefore shares an identical agonist profile with the presynaptic Y2 receptor at the peripheral sympathetic neuroeffector junction.
Actions of dipyridamole on endogenous and exogenous noradrenaline in the dog mesenteric vein
Authors: Li Yajun , Zhang Guoliang , Suzuki Hikaru , Kuriyama Hirosi 
Published: July 2012

In the isolated mesenteric vein of the dog, dipyridamole inhibited both the excitatory junction potential (e.j.p.) and the slow depolarization evoked by perivascular nerve stimulation, to 60–70% of control, with no change in the postjunctional membrane potential. These inhibitory actions of dipyridamole were not modified by 8‐phenyltheophylline or phentolamine, suggesting that the inhibition did not involve either the actions of endogenous adenosine or the prejunctional α‐autoregulation mechanism.
Dipyridamole did not produce any detectable effects on either the facilitation process of the e.j.ps or the postjunctional membrane depolarization produced by exogenously applied noradrenaline (NA).
Dipyridamole reduced the outflow of both the NA and the 3,4‐dihydroxyphenylglycol (DOPEG) evoked by perivascular nerve stimulation to below 10% of control, the effect being much greater than that of exogenously applied adenosine (to about 90% of the control).
Exogenously‐added NA was degraded by incubation with a segment of the vein. Dipyridamole itself produced degradation of NA and accelerated the NA‐induced degradation. By contrast, pyrogallol, but not pargyline or imipramine, prevented the NA‐induced degradation.
It is suggested that dipyridamole degrades NA directly, and also indirectly through activation of catechol‐O‐methyl transferase, with no alteration of the activity of monoamine oxidase or of the uptake mechanisms of NA into nerve terminals.
Ion transport in cultured epithelia from human sweat glands: comparison of normal and cystic fibrosis tissues
Authors: Brayden D.J. , Pickles R.J. , Cuthbert A.W. 
Published: July 2012

Cultured epithelia derived from whole human sweat glands, isolated secretory coils, isolated reabsorptive ducts and whole glands from cystic fibrosis (CF) subjects have been used to examine drug sensitivity by use of short circuit current recording.
Short circuit current increases were observed with lysylbradykinin, carbachol and histamine in epithelia of different origins. All responses were due to stimulation of electrogenic sodium absorption, evidenced by the inhibition of these responses by amiloride. The latter also abolished the basal current. The terpenes, thapsigargin and forskolin had no effect on transport.
The stimulation of a sodium current by agonists was dependent upon calcium, responses being inhibited by lanthanum ions and EGTA. Further A23187 induced a sodium current.
Pronounced oscillations in the sodium currents were a feature of the responses, implying synchronous, regulated cell activity.
Forskolin produced a ten fold increase in adenylate cyclase activity. All agonists listed in 2 except forskolin caused an increase in intracellular calcium [Ca]i, [Ca]i responses in CF cells were not different from those of normal cells, except with thapsigargin where the responses were smaller.
It is concluded that in culture, cells develop ductal characteristics, whether derived from normal or CF glands, coils or ducts. An increase in [Ca]i followed by activation of calcium‐sensitive potassium channels and apical membrane hyperpolarization may be the major mechanism for increasing sodium influx.
Evidence that part of the NANC relaxant response of guinea‐pig trachea to electrical field stimulation is mediated by nitric oxide
Authors: Li Chun Guang , Rand Michael J. 
Published: July 2012

The nitric oxide (NO) synthesis inhibitors NG‐monomethyl l‐arginine (l‐NMMA) and l‐nitroarginine methyl ester (l‐NAME) reduced relaxations of guinea‐pig tracheal smooth muscle elicited by stimulation of intramural non‐adrenergic, non‐cholinergic (NANC) nerves, but d‐NMMA had no effect. l‐NAME was 10–30 times more potent than l‐NMMA. Relaxations produced by sodium nitroprusside and vasoactive intestinal polypeptide (VIP) were not affected by l‐NMMA or l‐NAME.
The inhibitory effect of l‐NMMA on NANC‐mediated relaxations was partially reversed by l‐arginine but was not affected by d‐arginine.
VIP antibody and α‐chymotrypsin abolished or greatly reduced the relaxant action of VIP and reduced relaxations elicited by stimulation of NANC nerves; the residual NANC relaxation was further reduced by l‐NAME.
The results suggest that NO and VIP are mediators of NANC‐induced relaxations of guinea‐pig tracheal smooth muscle. We propose the term ‘nitrergic’ to describe transmission processes which are mediated by NO.
Protection induced by cholecystokinin‐8 (CCK‐8) in ethanol‐induced gastric lesions is mediated via vagal capsaicin‐sensitive fibres and CCKA receptors
Authors: Evangelista S. , Maggi C.A. 
Published: July 2012

We have investigated the effect of intravenous injection of cholecystokinin‐8 (CCK‐8) and other peptides on gastric lesion formation in response to an intragastric perfusion with 25% ethanol in rats anaesthetized with urethane.
Intravenous injection of CCK‐8 (50–100 nmol kg−1), but not bombesin (1–100 nmol kg−1), calcitonin gene‐related peptide (1–50 nmol kg−1), neurokinin A (1 μmol kg−1) or substance P (100 nmol kg−1), induced protection against gastric haemorrhagic lesions produced by ethanol.
The CCKA‐antagonist L‐364,718 (2.45 μmol kg−1, i.v.) increased the lesion index induced by ethanol and reversed the protective effect of CCK‐8 (50 nmol kg−1, i.v.). The CCKB‐antagonist L‐365,260 (5 μmol kg−1, i.v.) and a lower dose of L‐364,718 (0.25 μmol kg−1, i.v.) were ineffective.
The gastric protective effects afforded by CCK‐8 (50 nmol kg−1, i.v.) were not observed in vagotomized‐rats and were reduced by capsaicin pretreatment. In capsaicin‐pretreated rats there was a worsening of gastric lesions induced by ethanol‐perfusion as compared to those observed in vehicle‐pretreated rats.
These results demonstrate that the mucosal protective effect of CCK‐8 involves, at least in part, the activation of CCKA‐receptors and is mediated by vagal capsaicin‐sensitive fibres.
Phorbol dibutyrate enhances local anaesthetic action
Authors: Austin S. , McGivern J. , Scholfield C.N. 
Published: July 2012

Synaptically‐evoked field responses were elicited by stimulation of the lateral olfactory tract of rat olfactory cortex slices maintained in vitro.
Various concentrations of lignocaine (5–500 μm) were applied to the solution bathing the slices. These produced dose‐dependent depressions of the synaptically‐evoked potential over the concentration range 20–500 μm. The responses completely recovered on washing out the lignocaine. Similar depressions were also noted for procaine (100–1000 μm).
In the 47 slices tested, application of β‐phorbol 12, 13‐dibutyrate (1 μm) increased the amplitude of the synaptic response (from 0.99 ± 0.05 to 1.36 ± 0.06 mV). β‐Phorbol 13‐monbutyrate (1 μm) had no effect.
In the presence of phorbol dibutyrate the depressant effect of lignocaine was increased: the EC50 changed from 91 ± 10 to 24 ± 2 μm (a mean potency increase of 3.47 ± 0.14). A similar increase in potency for procaine was observed with phorbol dibutyrate (from 264 ± 23 to 49 ± 9 μm: a 5.49 ± 0.82 increase in potency). If the tissue was pre‐equilibrated in a concentration of lignocaine which produced a 60–80% depression, addition of phorbol ester caused a complete abolition of the evoked potential.
β‐Phorbol 13‐monobutyrate (1 μm) had no effect on the potency of lignocaine.
The Na and K currents generating the action potential in the presynaptic nerve terminals were unaffected by phorbol dibutyrate. The depressant effect of lignocaine on these currents was not modified by phorbol dibutyrate.
The potentiation of lignocaine could not be accounted for by membrane depolarization or by non‐specific actions of phorbol dibutyrate, and was distinct from the action on transmitter release. Therefore, it seems likely that protein kinase C activation was responsible for the modified action of lignocaine, although the mechanism for this is unclear.
Relation between adrenergic neurogenic contraction and α1‐adrenoceptor subtypes in dog mesenteric and carotid arteries and rabbit carotid arteries
Authors: Muramatsu Ikunobu 
Published: July 2012

We examined the distribution of α1‐adrenoceptor subtypes and their relation to adrenergic neurogenic contraction induced by electrical transmural stimulation in the dog mesenteric and carotid arteries and the rabbit carotid artery.
In the dog mesenteric artery, contraction to noradrenaline was competitively inhibited by HV723 (pKB = 9.37) and prazosin (pKB = 8.40). Pretreatment with chlorethylclonidine (CEC) slightly attenuated only the contractions induced by low concentrations of noradrenaline. Contraction induced by electrical transmural stimulation was inhibited at lower concentrations of HV723 than of prazosin.
In the dog carotid artery, contraction to noradrenaline was inhibited with higher affinity by prazosin (pKB = 9.82) than by HV723 (pKB = 8.47). Prozosin was also more potent than HV723 in inhibiting the contraction to electrical stimulation. Pretreatment with CEC markedly attenuated or abolished contraction to noradrenaline and electrical stimulation.
In the rabbit carotid artery, prazosin inhibited noradrenaline‐induced contraction biphasically (pKB = 9.91 and 8.60). After CEC pretreatment, contraction to noradrenaline was attenuated moderately and the high affinity site for prazosin was abolished. HV723 competitively inhibited the noradrenaline response with a similar pKB value (approximately 8.5) regardless of CEC treatment. Contraction to electrical stimulation was inhibited by prazosin more effectively than by HV723 in preparations not treated with CEC, while it was equipotently inhibited by both antagonists in CEC‐treated preparations.
These results suggest that the contractions induced by endogenous and exogenous noradrenaline are mediated through the same subtypes of α1‐adrenoceptor distributed in each artery; according to our recent subclassification: α1N subtype in the dog mesenteric artery, α1H subtype in the dog carotid artery and α1H and α1L subtypes in the rabbit carotid artery. Different susceptibility to α1‐adrenoceptor antagonists of sympathetic adrenergic responses in various blood vessels may be related to heterogeneous involvement of distinct α1‐adrenoceptor subtypes in the sympathetic response.
Existence of two components in the tonic contraction of rat aorta mediated by α1‐adrenoceptor activation
Authors: Nishimura Kanami , Ota Mikio , Ito Katsuaki 
Published: July 2012

The mechanisms involved in the contraction of rat aorta induced by the activation of α1‐adrenoceptors were studied. Phenylephrine induced a phasic contraction in the aorta incubated in Ca2+‐free medium containing 0.5 mm EGTA. Subsequent addition of Ca2+ induced a tonic contraction, which exhibited a stepwise development, an initial phase lasting 3 to 6 min (tonic‐I) followed by a superimposing second phase (tonic‐II).
2‐Nitro‐4‐carboxyphenyl‐N,N‐diphenylcarbamate, which has been reported to inhibit phosphatidylinositol turnover, and H‐7, a protein kinase C inhibitor, inhibited the tonic‐I phase more effectively than the tonic‐II phase. On the other hand, the tonic‐II phase was more sensitive to nifedipine and cromakalim.
The rate of 45Ca2+ influx during the tonic‐I phase in phenylephrine‐treated muscles was not different from that in untreated muscles, while that during the tonic‐II phase was significantly greater. Nifedipine inhibited the increased 45Ca2+ influx during the tonic‐II phase, whereas H‐7 did not affect the uptake during either phase.
These results suggest that the tonic contraction of rat aorta following α1‐adrenoceptor activation involves two different mechanisms: one is directly related to consequences of the polyphosphoinositide cascade, probably to protein kinase C, and the other dependent on Ca2+ influx through nifedipine‐sensitive Ca2+ channels.
Inhibitory effects of BAY u3405 on prostanoid‐induced contractions in human isolated bronchial and pulmonary arterial muscle preparations
Authors: Norel X. , Labat C. , Gardiner P.J. , Brink C. 
Published: July 2012

The thromboxane‐mimetic, U46619, was a more potent contractile agonist than prostaglandin D2 (PGD2), PGF2α or histamine in human isolated bronchial and pulmonary arterial muscle preparations.
Human isolated proximal bronchial muscles were less sensitive to contractile agents than distal bronchial preparations. However, the former tissues developed a greater contractile force (Emax) when compared with results obtained in the latter tissues.
BAY u3405 attenuated the contractions induced by U46619, PGF2α and PGD2 in both human isolated bronchial and pulmonary arterial muscle preparations.
BAY u3405 did not alter histamine concentration‐effect curves nor the relaxation induced by Butaprost (TR4979) in human isolated bronchial muscle preparations. In addition BAY u3405 did not modify the relaxation induced by PGI2 in isolated pulmonary arterial muscle preparations.
The contractions induced by different prostaglandins were blocked by BAY u3405, suggesting a common functional site for these agents found both on human bronchial and pulmonary arterial muscles.