bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of arachidonic acid and non‐steroidal anti‐inflammatory drugs on intrapulmonary airways of the guinea‐pig
Authors: Clay T. P. , Fenske D. C. 
Published: July 2012

A method is described in which changes in intrapulmonary airway tone of guinea‐pig isolated lungs are reflected by changes in intraluminal perfusion pressure.
A supramaximal dose of arachidonic acid (AA) (61 μm) was found to have little on no action on baseline perfusion pressure. However, following elevation of perfusion pressure with histamine, AA caused a dose‐dependent pressure decrease. This was also mimicked by prostaglandin E1 (PGE1) and PGE2.
AA induced a reduction of histamine elevated perfusion pressure which was inhibited, dose‐dependently, by several non‐steroidal anti‐inflammatory agents including indomethacin, phenylbutazone, aspirin, benoxaprofen, BW755C and phenidone. Their respective rank order of potency appeared to correlate with their activity against microsomal cyclo‐oxygenase.
Indomethacin, phenylbutazone and aspirin induced augmentation of the elevated perfusion pressure due to histamine, whereas BW755C did not.
We suggest that the primary arachidonate metabolite present in intrapulmonary airways following histamine‐induced constriction is probably a relaxant of the E series. However, our data suggest that both cyclo‐oxygenase and lipoxygenase products are associated with the maintenance of airway tone.
Effect of cyclosporin A and inhibitors of arachidonic acid metabolism on blood flow and cyclo‐oxygenase products in rat skin allografts
Authors: Fan T.‐P.D. , Lewis G.P. 
Published: July 2012

Using skin blood flow as a measurement of skin graft rejection in rats, it has been shown that in both isografts and allografts the blood flow at first increases above the normal, after which the flow in isografts returns to normal while that in allografts ceases at the onset of rejection.
Cyclosporin A (CSA) 5–40 mg kg−1 intramuscularly produced a dose‐related inhibition of graft rejection and the pattern of blood flow in the treated allografts became similar to that in isografts in that it remained about 20% above normal throughout the period of treatment.
Indomethacin (Indo), inhibitor of cyclo‐oxygenase and benoxaprofen (Ben), inhibitor of cyclo‐oxygense and lipoxygenase, caused an enhancement of the onset of rejection and an early cessation of blood flow in allografts.
The total content of 4 cyclo‐oxygenase products (COP), (prostaglandin E2 (PGE2), PGF2α, 6‐oxo‐PGF1α and thromboxane B2 (TxB2)) increased both in isografts and allografts, but when individual COP were expressed as a percentage of the total, only 6‐oxo‐PGF1α (the stable metabolite of prostacyclin) increased in allografts.
This increased proportion was reduced to normal by a dose of CSA which prolonged graft survival. Indo and Ben partially inhibited COP formation and in particular that of 6‐oxo‐PGF1α. In addition, CSA caused a dose‐related inhibition of the prostacyclin produced by zymosan‐activated macrophages.
These findings in the rat suggest that prostacyclin is partly responsible for the increase in blood flow in allografts prior to rejection; that CSA inhibits both the recruitment of prostacyclin‐producing macrophages and prostacyclin formation directly; and that inhibitors of cyclo‐oxygenase enhance skin graft rejection by abrogating the immunoregulatory activity of prostacyclin.
Comparative effects of verapamil and sodium nitroprusside on contraction and 45Ca uptake in the smooth muscle of rabbit aorta, rat aorta and guinea‐pig taenia coli
Authors: Karaki H. , Nakagawa H. , Urakawa N. 
Published: July 2012

The effects of verapamil and sodium nitroprusside on muscle tension and 45Ca uptake activated in different ways were compared in rabbit aorta, rat aorta and guinea‐pig taenia coli.
In rabbit aorta, K‐induced contraction was specifically inhibited by verapamil and noradrenaline‐induced contraction by sodium notroprusside. In rat aorta, both K‐induced and noradrenaline‐induced contractions were inhibited by verapamil or by sodium nitroprusside also. In taenia, both K‐ and histamine‐induced sustained contractions were inhibited by verapamil but not by sodium nitroprusside. The effect of varapamil was competitively antagonized by external Ca, while that of sodium nitroprusside was not.
High K, noradrenaline and histamine increased the rate of 45Ca uptake in aortae and taenia. In rabbit aorta the increment in response to high K was specifically inhibited by verapamil and the increment induced by noradrenaline was specifically inhibited by sodium nitroprusside. In rat aorta, increments induced by both high K and noradrenaline were inhibited by verapamil and by sodium nitroprusside. In taenia, the increments induced by high K and by histamine were inhibited by verapamil but not by sodium nitroprusside.
These results suggest different characteristics of Ca entry systems in these smooth muscles. In rabbit aorta, there seem to be two Ca channels, one of which is activated by high K and inhibited by verapamil, while the other is activated by noradrenaline and inhibited by sodium nitroprusside. In rat aorta, both K‐ and noradrenaline‐activated Ca pathways are sensitive to both verapamil and sodium nitroprusside whereas, in taenia, both K‐ and histamine‐activated Ca pathways are sensitive only to verapamil.
Effects of KCl on 45Ca uptake and efflux in the rat vas deferens
Authors: Hay D.W.P. , Wadsworth R.M. 
Published: July 2012

The effects of KCl 160 mm on 45Ca uptake and efflux in the rat isolated vas deferens were investigated using a modification of the lanthanum method and a superfusion system respectively.
In the prostatic half, basal cellular 45Ca uptake was 679 ± 21 nmol g−1 tissue wet weight and KCl 160 mm increased this by 155%. In the epididymal half, basal cellular 45Ca uptake was 730 ± 28 nmol 45Ca g−1 and KCl 160 mm increased this by 46%.
Verapamil 2.04 JAM or nifedipine 0.29 μm had no or little effect on basal 45Ca efflux or on basal 45Ca uptake. The KCl‐induced increase in 45Ca uptake in both halves was inhibited by verapamil 2.04 μm or nifedipine 0.29 μm, concentrations which markedly reduce the contractile response. It is concluded that high K+ contracts the rat vas deferens by stimulation of the entry of extracellular Ca2+ to the intracellular compartment.
KCl 160 mm produced a large, rapid and reversible increase in the rate of 45Ca efflux into Ca2+‐containing and Ca2+‐free Krebs‐Henseleit solutions, which was not inhibited by verapamil 2.04 μm, nifedipine 0.29 μm or nitroprusside 1,678 μm.
The relative size of the slow component of 45Ca efflux was larger in the prostatic half compared to the epididymal half of bisected tissues, suggesting that the postulated high affinity binding sites are predominant in this region. However, the rates of the fast and slow components of 45Ca efflux from prostatic and epididymal halves were identical. KCl 160 mm produced a similar increase in 45Ca efflux in prostatic and epididymal halves.
Influence of plasma protein on the inhibitory effects of indocyanine green and bromcresol green on pulmonary prostaglandin E1 extraction
Authors: Dawson Christopher A. , Linehan John H. , Rickaby David A. , Roerig David L. 
Published: July 2012

The purpose of this study was to examine the influence of plasma protein on the inhibitory effects of the anionic dyes indocyanine green and bromcresol green on prostaglandin E1 (PGE1) uptake by the lungs.
Dog lung lobes were isolated and perfused with either autologous plasma or Krebs‐Ringer bicarbonate solution (KRB) containing no protein but with dextran used as a colloid.
PGE1 uptake was determined by injecting a bolus, containing radiolabeled PGE1 into the lobar artery and then analysing ethanolic extracts of the venous effluent for radioactivity in PGE1 and PGE1 metabolites by thin layer chromatography and scintillation counting.
When the lobes were perfused with KRB, bromcresol green at an average initial concentration of 28.5 μm, reduced PGE1 by an average of 56%. When the lobes were perfused with plasma, similar concentrations of bromcresol green reduced the uptake by less than 2%.
A similar result was obtained with indocyanine green, which at an average initial concentration of 17.5 μm reduced uptake by about 70% when the lobes were perfused with KRB, but when the lobes were perfused with plasma similar concentrations of the dye reduced uptake by less than 3.5%.
The results suggest that plasma protein binding interferes with the inhibitory effects of these dyes on PGE1 uptake in the lungs.
Mediators of arachidonic acid‐induced contractions of indomethacin‐treated guinea‐pig airways: leukotrienes C4 and D4
Authors: Burka John F. , Saad Maan H. 
Published: July 2012

Arachidonic acid (AA) (66 μm) induced contractions of indomethacin‐treated (8.4 μm) guinea‐pig tracheal and lung parenchymal preparations. Mepacrine (210 μm) treatment did not affect the magnitude of contraction induced by AA.
Normal and ovalbumin‐sensitized tissues responded identically to AA, and released equivalent amounts of the contractile mediators.
Nordihydroguaiaretic acid (100 μm) markedly reduced release of the contractile mediators and reduced AA‐induced contractions of the airways.
The mediators of AA‐induced, calcium ionophore A23187‐induced, and antigen‐induced contraction of the trachea and lung parenchyma were purified and identified by reverse‐phase high performance liquid chromatography to be leukotrienes C4 and D4, being present in an approximate ratio of 20:1.
Mepacrine‐treated trachea exhibited a smaller contractile response to stimuli (A23187 for normal tissues and ovalbumin for sensitized tissues). Addition of exogenous AA (66 μm) increased the magnitude of contraction, although not to the level observed on tissues not treated with mepacrine. There was no observable effect of AA on the response of mepacrine‐treated parenchyma to the ionophore or antigen.
It was concluded that (a) immunological sensitization does not alter AA metabolism via the lipoxygenase pathway in guinea‐pig airways and (b) the mediators of AA‐induced contraction are leukotrienes C4 and D4.
Differences between the prejunctional effects of phenylephrine and clonidine in guinea‐pig isolated atria
Authors: Ledda Fabrizio , Mantelli Laura 
Published: July 2012

The prejunctional effects of clonidine and phenylephrine were studied in guinea‐pig isolated atria by means of field stimulation of the sympathetic nerve terminals during the cardiac refractory period, in the presence of 1 μm atropine.
Clonidine (10–100 nm) produced a dose‐dependent decrease in the stimulus‐inotropic response curve; the IC50 for clonidine was increased about 70 times by the pretreatment of the preparations with 1 μm yohimbine. The effect of clonidine was not modified by 0.5 μm prazosin.
Unlike clonidine, phenylephrine (1–10 μm) induced a statistically insignificant increase in the contractile force of preparations stimulated at 4 Hz.
The inhibitory effect of phenylephrine (1–10 μm) was partially prevented by either 1 μm yohimbine or 0.5 μm prazosin. However, it was antagonized, to about the same degree as that observed with clonidine, by the pretreatment of the preparations with both 1 μm yohimbine and 0.5 μm prazosin.
The results seem to indicate that one component of the prejunctional effects of phenylephrine may be mediated by presynaptic α‐adrenoceptors belonging to the α1‐subtype.
Hyperalgesia produced by intrathecal substance P and related peptides: desensitization and cross desensitization
Authors: Moochhala S.M. , Sawynok J. 
Published: July 2012

The hyperalgesic effect of intrathecally administered substance P (SP), physalaemin, eledoisin and eledoisin‐related peptide (ERP) was investigated in the rat tail flick test.
Hyperalgesia produced by SP (2.5–15 μg, 1.9–11 nmol) was maximal 10–20 min after injection, lasted 30 min and was dose‐related. The effect was mimicked by all of the peptides examined. The rank order of potency was physalaemin > SP > eledoisin > ERP.
Desensitization to the hyperalgesic effect of SP was produced by three repeated intrathecal injections. Rats desensitized to SP no longer responded to physalaemin or ERP, indicating cross‐desensitization. Phentolamine continued to produce hyperalgesia following such desensitization.
The demonstration of a hyperalgesic effect for SP provides further support for a role for SP in nociceptive transmission. The receptor mediating this effect appears to be a SP‐P subtype. Cross‐desensitization between peptides suggests an action on the same receptor.
A study of [d‐Pro2, d‐Phe7, d‐Trp9]‐substance P and [d‐Trp7,9]‐substance P as tachykinin partial agonists in the rat colon
Authors: Bailey S. J. , Jordan C.C. 
Published: July 2012

Two substance P (SP) analogues, [d‐Pro2, d‐Phe7, d‐Trp9‐SP (DPDPDT) and [d‐Trp79]‐SP (DT7,9), previously described as tachykinin antagonists, have been shown to contract the rat colon muscularis mucosae preparation. The maximum response exhibited by these analogues was about 30% that of the SP maximum, suggesting that they were acting as partial agonists relative to SP.
The responses to DPDPDT were unaffected by pretreatment with mepyramine, methysergide or [Sar1, Ile5, Ala8]‐angiotensin II, which abolished the responses to histamine, 5‐hydroxytryptamine (5‐HT) and angiotensin II, respectively. Methysergide also did not affect the responses to DT79; the other antagonists were not tested against this analogue. Indomethacin and cimetidine also had no inhibitory effect. Atropine (2 μm) was present in all experiments to prevent indirect muscarinic effects.
Phenoxybenzamine did not affect the dose‐response curves to SP, eledoisin‐related peptide (ERP), kassinin, eledoisin or physalaemin, nor did it affect the responses to individual doses of DPDPDT or DT79. However, in the absence of atropine, it shifted the carbachol dose‐response curve markedly to the right, and reduced its maximum.
The tachykinin antagonist [d‐Pro4, d‐Trp7,9,10]‐SP4–11 reduced the responses to individual matched doses of DPDPDT, DT79 and SP to the same degree, whilst leaving responses to 5‐HT or angiotensin II unaffected. This suggested that DPDPDT and DT79 were acting at the same receptor as SP.
The inhibitory effects of DPDPDT on responses to SP, ERP and kassinin, and that of DT79 on responses to SP, were analysed. All four combinations yielded data compatible with an interaction at only one receptor, although DPDPDT appeared slightly more potent at inhibiting responses to kassinin.
The results are discussed in the light of the proposed existence of multiple tachykinin receptor subtypes. The possible influence of differential metabolism of tachykinin analogues is also considered.
Neuronal responses to noradrenaline in the cerebral cortex: evidence against the involvement of α2‐adrenoceptors
Authors: Bradshaw C.M. , Sheridan R.D. , Szabadi E. 
Published: July 2012

The technique of microelectrophoresis was used to test the hypothesis that α2‐adrenoceptors are involved in mediating the excitatory responses of single neurones to noradrenaline in the somatosensory cerebral cortex of the rat.
In the first series of experiments the effects of two α2‐adrenoceptor antagonists, yohimbine and idazoxan (RX‐781094), were compared on excitatory responses to noradrenaline, phenylephrine and acetylcholine. The response to noradrenaline was not more susceptible to antagonism by these drugs than the response to the α1‐adrenoceptor stimulant, phenylephrine. Yohimbine antagonized responses to all three agonists equally, while idazoxan antagonized responses to noradrenaline and phenylephrine equally with relative preservation of responses to acetylcholine.
In the second series of experiments the effects of the selective α2‐adrenoceptor stimulant, UK‐14304, were examined. UK‐14304 produced weak and inconsistent excitations on a small number of cells; however, most of the cells did not respond to this drug. When applied continuously using low ejection currents, UK‐14304 selectively and reversibly antagonized responses to noradrenaline and phenylephrine without affecting responses to acetylcholine.
These results suggest that, in the somatosensory cortex of the rat, neuronal excitation to noradrenaline is unlikely to be mediated either wholly or partly by α2‐adrenoceptors. The antagonism of neuronal responses to noradrenaline and phenylephrine by idazoxan probably reflects the α1‐adrenoceptor antagonistic properties of the drug which is known to occur at higher concentrations. The low agonistic potency of UK‐14304 and the antagonism of responses to noradrenaline and phenylephrine by UK‐14304 suggest that this drug, like clonidine, may act as a partial agonist at α1‐adrenoceptors.
3‐Hydroxy‐N,N‐dimethylpiperidinium: a precursor of a false cholinergic transmitter
Authors: Hemsworth B.A. , Shreeve S.M. , Veitch G.B.A. 
Published: July 2012

A cyclic choline analogue, 3‐hydroxy‐N,N‐dimethylpiperidinium, has been shown to be transported into a crude preparation of synaptosomes by high and low affinity transport mechanisms. Under conditions favouring the high affinity system the synaptosomes metabolized approximately 50% of the accumulated analogue to 3‐acetoxy‐N,N‐dimethylpiperidinium, which was detected by paper electrophoresis.
The phrenic nerve endplate region of a mouse hemidiaphragm accumulated 3‐hydroxy‐N,N‐dimethylpiperidinium on nervous stimulation. This tissue metabolized approximately 60% of the accumulated analogue to the acetylated derivative which was released on nervous stimulation into the bathing medium.
Compared to acetylcholine, 3‐acetoxy‐N,N‐dimethylpiperidinium was shown to be 57 times less potent an agonist at the nicotinic receptors of the frog rectus abdominis muscle and 162 times less potent an agonist at the muscarinic receptors of the guinea‐pig ileum.
It is concluded that 3‐hydroxy‐N,N‐dimethylpiperidinium is a precursor of a false cholinergic transmitter.
Vascular effects of ginsenosides in vitro
Authors: Chen Xiu , Gillis C. Norman , Moalli Richard 
Published: July 2012

Ginsenosides (saponins extracted from Panax ginseng) elicit qualitatively and quantitatively different responses in isolated, contracted ring preparations of different blood vessels from rabbits, dogs and humans.
Ginsenosides themselves did not affect the tone of ‘resting’ isolated blood vessels directly, but contracted slightly the renal vein of rabbits at the maximum concentration tested. The mixture caused relaxation of the noradrenaline (NA) or prostaglandin F2α (PGF2α‐induced contraction of the pulmonary artery and intrapulmonary artery of rabbits, and the PGF2α‐induced contraction of the canine mesenteric vein.
Ginsenosides potentiated, in a concentration‐dependent manner, the contractile responses of renal veins of dogs and rabbits to PGF2α
The reason for such heterogeneous responses of different blood vessels to ginsenosides in unknown. It is suggested that either potentiation of contraction or relaxation of contracted blood vessels might be mediated by interaction with endogenous vasoactive substances. The potentiation of PGF2α‐induced contraction may be related to the reduction of renal blood flow observed in anaesthetized dogs. The simultaneous contraction and relaxation effects may explain its biphasic actions on blood pressure.
Anti‐arrhythmic effects of (‐)‐carnitine chloride and its acetyl analogue on canine late ventricular arrhythmia induced by ligation of the coronary artery as related to improvement of mitochondrial function
Authors: Imai Shoichi , Matsui Kazuki , Nakazawa Mikio , Takatsuka Naoki , Takeda Keisuke , Tamatsu Hirokuni 
Published: July 2012

Using the two‐stage coronary ligation method, first described by Harris, (1950), anti‐arrhythmic effects (AAE) of (‐)‐carnitine chloride (LCC) and acetyl (‐)‐carnitine chloride (ALCC) were studied in conscious unrestrained dogs in comparison with those of disopyramide (D). Two‐stage ligation of the coronary artery resulted in a significant decrease in the myocardial free carnitine content.
Intravenous administration of LCC (300 mg kg−1) and D (5 mg kg−1) suppressed the ventricular arrhythmia induced by coronary ligation after 24 hours. ALCC (300 mg kg−1) was found to be less potent.
An improvement of the mitochondrial function (respiratory control index (RCI) and oxidative phosphorylation rate (OPR)) was noted with LCC and ALCC and there was a linear correlation between AAE expressed as reduction of arrhythmic ratio and improvement in the OPR, whereas there was no improvement in mitochondrial function after D.
Plasma carnitine concentration was increased after administration of LCC, attaining the value of around 8 mm at 10 min after 300 mg kg−1. At 60 min, the plasma carnitine concentration was still about half as high as at 10 min. After ALCC, both acetyl carnitine and free carnitine were found in the plasma. The concentration of the former was decreased after attaining a peak value of around 0.2 mm at 10 min, while the plasma concentration of free carnitine was gradually increased.
The anti‐arrhythmic effects of LCC and ALCC were ascribed to the improvement of mitochondrial oxidative phosphorylation, while effects other than the improvement of the mitochondrial activity were suggested as mechanisms of anti‐arrhythmic effects of D.
The actions of cirazoline on the rat vas deferens
Authors: Docherty J.R. , McGrath J.C. 
Published: July 2012

The pre‐ and postsynaptic effects of the α1‐agonist cirazoline were assessed in epididymal and prostatic portions of the rat isolated vas deferens.
Cirazoline produced a postsynaptic α1‐adrenoceptor mediated potentiation of the isometric contraction to single pulse field stimulation in both prostatic and epididymal portions.
In epididymal portions, nifedipine (10 μM) greatly attenuated the postsynaptic α1‐receptor mediated potentiation of nerve mediated contractions, uncovering a presynaptic inhibitory action of cirazoline.
No evidence was found for α2‐antagonism by cirazoline. It is concluded that the previously reported antagonism of the presynaptic inhibitory effects of clonidine was due to postsynaptic potentiation of nerve‐mediated responses by cirazoline.
Post‐natal development of functional neurotransmission in rat vas deferens
Authors: MacDonald A. , McGrath J.C. 
Published: July 2012

Responses of the rat vas deferens to drugs and to field stimulation were examined in sexually immature rats.
The vasa from immature rats often exhibited spontaneous contractions and displayed greater sensitivity to the contractile effects of α‐adrenoceptor agonists.
The responses of the vasa from immature rats to single pulse field stimulation lacked the adrenergic component of the response although the non‐adrenergic component was present. The responses were antagonized by α2‐adrenoceptor agonists. In the presence of cocaine, an adrenergic component of the response did appear.
During trains of pulses the pre‐ and postjunctional effects of adrenergic transmission which are found in adult rats were absent in vasa from immature rats.
Electron microscopic studies showed no qualitative differences in adrenergic innervation in vasa from immature and adult rats.
It is concluded that a state of ‘pre‐innervation supersensitivity’ associated with a lack of functional adrenergic transmission exists in the vas deferens of immature rats. The supersensitivity disappears and functional transmission develops during the period in which testosterone secretion increases in the rat. The reason for the lack of functional transmission at a time when the innervation appears to be morphologically mature is not clear but may be due to the noradrenaline release mechanism not being fully operative.