bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nifedipine effects in severe myocardial ischaemia in the dog due to left anterior descending coronary occlusion with left circumflex coronary artery constriction
Authors: Szekeres L. , Udvary Éva , Végh Ágnes 
Published: July 2012

The effects of nifedipine were studied in a model of local myocardial ischaemia, comprising anaesthetized thoracotomized dogs in which a critical constriction of the left circumflex coronary artery (LCX) was combined with sudden occlusion of the left anterior descending coronary artery (LAD). Since more than one coronary artery is involved in ischaemic heart disease, the model seems to reflect the clinical situation very closely.
In this model, infusion of 1 μg kg−1 min−1 nifedipine increased myocardial blood flow within the stenosed area served by the LCX as well as in the myocardial region supplied by the LAD, mainly in the subepicardium. Accordingly, the drug reduced ischaemic ST‐segment elevation only in the epicardium.
It is suggested that nifedipine directed flow to the sub‐epicardium of the ischaemic area by improving the collateral circulation. This redistribution of flow resulted in a decrease in the endo/epicardial flow ratio.
Nifedipine did not change the inhomogeneity of electrical activation indicating that it has no effect on the ischaemia‐induced conduction delay. At the same time nifedipine was not able to reduce either the number of extrasystoles appearing in the early postocclusion and reperfusion phase or the incidence of ventricular fibrillation occuring mainly during reperfusion.
Binding of thromboxane A2/prostaglandin H2 agonists to human platelets
Authors: Halushka Perry V. , Kochel Pamela J. , Mais Dale E. 
Published: July 2012

The competition of [125I]‐9,11 dimethylmethano‐11,12 methano‐16‐(3‐iodo‐4‐ hydroxyphenyl)‐13, 14‐dihydro‐13‐aza 15αβ‐ω)‐tetranor‐thromboxane A2 ([125I]‐PTA‐OH), a thromboxane A2/prostaglan‐din H2 receptor antagonist, with a series of thromboxane A2/prostaglandin H2 (TXA2/PGH2) mimetics for binding to the putative TXA2/PGH2 receptor in washed human platelets was studied.
The rank order potency for the series of mimetics to compete with [125I]‐PTA‐OH for binding was compared with their rank order potency for induction of platelet aggregation. The rank order potency for the mimetics to compete with [125I]‐PTA‐OH for binding was ONO‐11113>SQ‐26655>U44069>U46619 = 9, 11‐azo PGH2>MB28767. This rank order potency was highly correlated with their rank order potency for inducing platelet aggregation (r = 0.992).
Changes in the intra or extracellular concentrations of Na+ did not have a significant effect on the competition between U46619 and [125I]‐PTA‐OH for binding to the putative receptor.
In summary, it appears that these TXA2/PGH2 mimetics activate human platelets through the putative TXA2/PGH2 receptor.
Dose‐related effects of pharmacological mediators on tracheal vascular resistance in dogs
Authors: Laitinen Lauri A. , Laitinen M. Annika , Widdicombe J.G. 
Published: July 2012

Various doses of mediators were tested on tracheal vascular resistance in dogs anaesthetized with pentobarbitone. Tracheal vascular resistance was determined by perfusing the cranial tracheal arteries at constant flows and measuring inflow pressures.
All drugs produced dose‐related changes in vascular resistance.
The peptides bradykinin, substance P and vasoactive intestinal peptide (VIP) each had similar vasodilator potencies and were much more powerful than histamine, methacholine and salbutamol.
Platelet activating factor (Paf) was a weaker dilator than the peptides. Prostaglandins D2, E1 and F2α had wide dilator potency ranges, PGE, being very effective even at low concentrations.
Phenylephrine, an α‐adrenoceptor agonist, was the only drug tested that always increased vascular resistance.
All the drugs studied also had effects on the contralateral tracheal vascular resistance.
Effects of local anaesthetics on short‐term desensitization of guinea‐pig taenia caecum to histamine
Authors: Hishinuma Shigeru , Uchida Masaatsu K. 
Published: July 2012

Short‐term desensitization to histamine was induced by incubating guinea‐pig taenia caecum with 10−4 m histamine for 30 min (desensitizing incubation) in normal Locke‐Ringer solution or Ca‐free Locke‐Ringer solution containing 0.2 mm EGTA. This desensitization was measured as a reduction of the maximal contractile response.
The effects of the presence of local anaesthetics during the desensitizing incubation were examined. Results showed that tetracaine, procaine, procainamide, oxybuprocaine and lignocaine inhibited the desensitization, whereas dibucaine, benzocaine and mepivacaine did not.
The inhibitory effects of these drugs on the desensitization were not correlated with their lipid solubility nor with the potency of their known effects, such as membrane stabilization, Ca channel blockade, calmodulin antagonism, or inhibition of C‐kinase.
It is concluded that the inhibitory effects of local anaesthetics on the desensitization are not due to their non‐specific membrane‐stabilizing effects per se, but to some other action.
Pharmacological differences between two muscarinic responses of the rat superior cervical ganglion in vitro
Authors: Newberry N.R. , Priestley T. 
Published: July 2012

Pharmacological differences have been observed between the muscarinic agonist‐induced depolarizing and hyperpolarizing responses of the rat isolated superior cervical ganglion.
Pirenzepine (0.3 μm) selectively reduced the depolarizing response and unmasked the hyperpolarizing response. No such selectivity was observed with a concentration of N‐methylatropine which was equipotent with pirenzepine in antagonizing the depolarizing response.
The neuromuscular blocking agents gallamine (10 μm) and pancuronium (3 μm) exhibited the oppositive selectivity to pirenzepine, both dramatically reduced the hyperpolarization but only slightly antagonized the depolarization.
The potencies of a range of agonists in evoking the depolarizing and hyperpolarizing responses, the latter in the presence of 0.3 μm pirenzepine, have been determined. Methylfurmethide failed to hyperpolarize the ganglion at concentrations which evoked maximal depolarizations.
The muscarinic hyperpolarization did not appear to be mediated by the secondary release of catecholamines.
It was concluded that the two muscarinic responses on the rat superior cervical ganglion, the slow depolarization and faster hyperpolarization, are mediated by different muscarinic receptor subtypes.
Effects of reserpine and 6‐hydroxydopamine on the adrenergic and purinergic components of sympathetic nerve responses of the rabbit saphenous artery
Authors: Warland Jennifer J.I. , Burnstock Geoffrey 
Published: July 2012

The effects of reserpine and of 6‐hydroxydopamine on the contractions of the rabbit isolated saphenous artery produced by stimulation of the sympathetic nerves were studied.
In vessels exposed to reserpine, substantial contractions to nerve stimulation were recorded despite a 95.7% reduction in the noradrenaline content of the tissue. These responses of the vessel were not significantly affected by the α1‐antagonist, prazosin, whereas after desensitization of the P2‐purinoceptor with α,β‐methylene ATP, no response to nerve stimulation remained.
In vessels exposed to 6‐hydroxydopamine, no nerve‐mediated responses were observed.
Noradrenaline‐containing nerves were observed by fluorescence histochemistry in control tissues, but were not observed in tissues treated with reserpine or 6‐hydroxydopamine.
The potencies of ATP and histamine were not significantly affected by reserpine or 6‐hydroxydopamine treatment. However, there was a slight supersensitivity to noradrenaline in reserpine‐treated and 6‐hydroxydopamine‐treated vessels compared with that of control vessels. Prazosin was selective for α‐adrenoceptors, while α,β‐methylene ATP was selective for P2‐purinoceptors.
These results substantiate the finding that ATP and noradrenaline are sympathetic cotransmitters in the rabbit isolated saphenous artery, and demonstrate that ATP can act as a transmitter independently of noradrenaline in this vessel.
Bradykinin‐stimulated prostaglandin synthesis in conscious rabbits
Authors: Warren J.B. , Ritter J.M. , Hickling N.E. , Barrow S.E. 
Published: July 2012

Bradykinin was infused intravenously into conscious rabbits to determine its effect on the concentration of prostaglandins in plasma. 6‐Oxo‐prostaglandin (PG) F1α, the stable hydrolysis product of prostacyclin, and 13,14‐dihydro‐15‐oxo‐PGF2α, a metabolite derived from PGE2 and PGF2α, were measured by gas chromatography‐electron capture mass spectrometry.
Incremental infusions of bradykinin (0.4‐3.2 μg kg−1 min−1) increased plasma concentrations of both 6‐oxo‐PGF1α and 13,14‐dihydro‐15‐oxo‐PGF2α.
Aspirin (10 mg kg−1, i.v.) inhibited bradykinin‐stimulated 6‐oxo‐PGF1α and 13,14‐dihydro‐15‐oxo‐PGF2α synthesis at 30 min and 6 h. At 24 h, the mean bradykinin‐stimulated 13,14‐dihydro‐15‐oxo‐PGF2α concentration was 66% of its original value, whilst 6‐oxo‐PGF1α remained substantially inhibited.
The different rates of recovery of bradykinin‐stimulated production of the two prostaglandins after inhibition by aspirin suggests that intravenous bradykinin stimulates prostacyclin and PGE2/PGF2α production in distinct cell populations which synthesize cyclo‐oxygenase at different rates.
Purinergic and non‐purinergic innervation in the cerebral arteries of the dog
Authors: Muramatsu Ikunobu , Kigoshi Shigeru 
Published: July 2012

Possible involvement of sympathetic purinergic transmission in the neurogenic response of dog cerebral and basilar arteries was examined with the use of α,β‐methylene ATP and adrenoceptor, cholinoceptor blocking agents.
In the isolated basilar arteries, electrical transmural stimulation produced a transient contraction which was frequently followed by a relaxation. This transient contraction was abolished after desensitization of P2‐purinoceptors with α,β‐methylene ATP or by treatment with guanethidine. The relaxant response induced by electrical stimulation was also attenuated but was not abolished by such treatments. Prazosin, propranolol and atropine had no significant effect on the responses to electrical stimulation. Yohimbine augmented both the contractile and relaxant responses.
In most preparations of the dog middle cerebral arteries, electrical transmural stimulation produced only a relaxation. This relaxation was little affected after treatment with α,β‐methylene ATP or guanethidine, and was not inhibited by the other adrenoceptor and cholinoceptor blocking agents.
Tetrodotoxin abolished the responses induced by electrical transmural stimulation in both the basilar and middle cerebral arteries.
Exogenous ATP (10−6 and 10−5 m) produced a transient contraction followed by a relaxation of the basilar arteries and a relaxation of the middle cerebral arteries. Desensitization of P2‐purinoceptors abolished the contractile response to ATP without affecting the amplitude of relaxation.
In the basilar and middle cerebral arteries preincubated with [3H]‐noradrenaline, electrical transmural stimulation evoked an increase in 3H‐efflux and this response was markedly inhibited by guanethidine or tetrodotoxin but was not affected by α,β‐methylene ATP. Yohimbine increased the evoked 3H‐efflux.
These findings indicate that cerebral arteries of the dog are innervated by sympathetic purinergic nerves and non‐sympathetic nerves which liberate unknown vasodilator substance(s), and that the former nerves are more dominant in the neurogenic response to electrical stimulation of the dog basilar artery than in the middle cerebral artery.
Pharmacological profile of PD 117302, a selective κ‐opioid agonist
Authors: Leighton G.E. , Johnson M.A. , Meecham K.G. , Hill R.G. , Hughes J. 
Published: July 2012

PD 117302, a new nonpeptide opioid compound shown in in vitro studies to be a selective κ‐opioid agonist, has been evaluted in vivo for antinociceptive activity and other effects characteristic of κ‐receptor activation.
Dose‐related long lasting antinociception was produced by PD 117302 against a mechanical noxious stimulus in rats following intravenous, subcutaneous or oral administration.
PD 117302 was effective in raising the nociceptive threshold to mechanical and chemical but not to thermal noxious stimuli in the mouse. This effect was attenuated in animals pretreated with the opioid antagonist naloxone.
In addition to producing antinociception, PD 117302 also caused naloxone‐reversible locomotor impairment and diuresis, effects that are typical of κ‐agonists.
PD 117302 did not cause respiratory depression, inhibition of gastrointestinal motility or naloxone‐precipated withdrawal jumping in mice, effects that are associated with actions at the μ‐opioid receptor.
The pharmacological profile of PD 117302 in vivo is consistent with in vitro data suggesting that PD 117302 is a selective agonist at the κ‐opioid receptor.
A comparison between the pattern of dopamine and noradrenaline release from sympathetic neurones of the dog mesenteric artery
Authors: Soares‐da‐Silva P. 
Published: July 2012

The release of dopamine and noradrenaline (NA), from the main trunk of the mesenteric artery and its proximal branches elicited by electrical nerve stimulation and K+, has been measured by using high pressure liquid chromatography with electrochemical detection.
Both stimuli released dopamine and NA. With the main trunk of the mesenteric artery, dopamine represented 8% of the NA tissue content; the dopamine/N A ratio in the catecholamine overflow caused by nerve stimulation or K+‐induced depolarization also averaged 8%. For the proximal branches the tissue dopamine/NA ratio was significantly greater than that observed to occur in the overflow caused by nerve stimulation and K+.
When the perifusion with a K+‐enriched medium was extended to 120min the amount of NA released from both the main trunk and the proximal branches progressively declined. The same pattern of release was observed for dopamine in the main trunk, whereas for the proximal branches dopamine overflow did not decline throughout the perifusion period. The addition of α‐methyl‐p‐tyrosine did not change the pattern of amine overflow.
Our interpretation of these results is that both dopamine and NA are derived from the same sympathetic neurone. In the proximal branches of the mesenteric artery dopamine and NA appear to be in two different storage structures, whereas in the main trunk both dopamine and NA are located in only one storage structure.
Protein kinase C and presynaptic modulation of acetylcholine release in rabbit hippocampus
Authors: Allgaier Clemens , Daschmann Beate , Huang Hua Yu , Hertting Georg 
Published: July 2012

The involvement of protein kinase C in the presynaptic modulation of stimulated acetylcholine release was investigated in rabbit hippocampus.
Slices of the rabbit hippocampus, labelled with [3H]‐acetylcholine, were superfused with medium and stimulated electrically during superfusion.
The protein kinase C activating phorbol ester 4β‐phorbol 12,13‐dibutyrate (4β‐PDB) enhanced the electrically evoked tritium overflow in a concentration‐dependent manner. Its biologically inactive 4α‐isomer was without any effect on transmitter release.
The protein kinase C inhibitor polymyxin B decreased the stimulation‐evoked tritium overflow and counteracted the enhancement of release caused by 4β‐PDB.
The stimulation‐evoked tritium overflow was facilitated when the muscarine receptor antagonist atropine was present. The effects of both atropine and 4β‐PDB, given in combination, were additive.
The net inhibition of the evoked tritium overflow caused by the muscarine receptor agonists carbachol and oxotremorine was similar, irrespective of whether 4β‐PDB was present or not.
Similar results to those for muscarine autoreceptor‐mediated inhibition, were obtained for inhibition of the stimulated tritium overflow caused by the adenosine receptor agonist (−)‐N6‐(R‐phenylisopropyl)‐adenosine ((−)‐PIA) and the opioid receptor agonist ethylketocyclazocine (EKC). The net inhibition of both agonists was independent of the presence of the phorbol ester.
The above results provide further evidence for participation of a presynaptically located protein kinase C in the modulation of acetylcholine release. However, the modulatory mechanisms which are coupled to presynaptic receptors and mediate inhibition of release seem not to be directly affected by protein kinase C.
κ‐Opioid agonists produce antinociception after i.v. and i.c.v. but not intrathecal administration in the rat
Authors: Leighton G.E. , Rodriguez R.E. , Hill R.G. , Hughes J. 
Published: July 2012

Nociceptive thresholds to noxious mechanical (paw pressure) and thermal (tail flick) stimuli were recorded in conscious rats. The effects of three selective κ‐opioid receptor agonists on the responses to these stimuli were determined following intravenous, intracerebroventricular or intrathecal administration. Results were compared with those obtained with morphine.
Following intravenous administration PD117302, U50488, U69593 and morphine produced steep parallel dose‐response curves indicating antinociceptive activity when evaluated in the paw pressure test. When U50488 and U69593 were tested at a single dose of 3.3 mg kg−1 no effect was seen in the tail flick test.
When given by the intrathecal route only morphine was effective at increasing the nociceptive threshold. PD117302, U50488 and U69593 were without effect in either the paw pressure or tail flick tests when tested at doses up to 100 μg per rat. PD117302 caused flaccid paralysis of the hindlimbs following intrathecal administration at the top dose tested. This effect was not reversible by naloxone.
All three κ‐opioid receptor agonists produced naloxone‐reversible antinociception in the paw pressure test, and to a lesser extent in the tail flick test, when injected directly into the third cerebral ventricle with the maximum effect occurring between 5 and 10 min after administration and declining back to control levels by 60 min. Morphine had a much slower onset of action with the peak effect being observed 30 min after dosing.
It is concluded that, under our experimental conditions in the rat, the antinociceptive effects of κ‐agonists are likely to be operated via an action at a supraspinal rather than a spinal site.
Some effects of leukotriene D4 on the mechanical properties of the guinea‐pig basilar artery
Authors: Nishiye Eiichiro , Itoh Takeo , Kuriyama Hirosi 
Published: July 2012

The effects of leukotriene D4 (LTD4) on the mechanical properties of smooth muscle cells from the guinea‐pig basilar artery were investigated in whole and chemically skinned muscle strips.
In strips with an intact endothelium, 5‐hydroxytryptamine (5‐HT; 10 μM), LTD4 and LTC4 (1 μM), STA2 (1 nm‐10nm) and high K+ (30 mm‐128mm) generated contractions. These comprised an initial phasic and subsequently generated tonic response with different amplitudes. Acetylcholine (ACh, 0.1–10 μm) inhibited and methylene blue (1–10 μm) enhanced the tonic component of these contractions in endothelium‐intact muscle strips. In endothelium‐denuded tissues, methylene blue had no effect on mechanical responses and ACh produced a further contraction in the presence of LTD4.
When the endothelium was removed, the amplitude of contractions induced by all tested stimulants markedly increased. In intact muscle strips, the order of potency for the production of a maximum response was; 128 mm K+ > STA2 > LTD4 = LTC4 = 5‐HT. Following removal of the endothelium; STA2 > 128 mm K+ > LTD4 = LTC4 ≤ 5‐HT.
In endothelium‐denuded strips, the selective LTD4 antagonists, ONO‐RS‐411 and FPL 55712 inhibited the LTD4‐induced contraction. In contrast, guanethidine, prazosin, yohimbine, atropine and mepyramine had no effect. Indomethacin and a thromboxane A2(TXA2) antagonist, ONO‐3708 also had no effect on LTD4‐induced contractions in endothelium‐denuded strips.
In endothelium‐denuded strips, nifedipine inhibited the tonic contraction induced by LTD4 but not the phasic component. In Ca2+‐free solution containing 2 mm EGTA, LTD4 produced only the phasic contractions.
In saponin‐treated chemically skinned muscle strips, LTD4 had no effect on either the pCa‐tension relationship or on the release of Ca2+ from intracellular stores. However, inositol 1,4,5‐trisphosphate released Ca2+ from the stores and 1,2‐diolein, an activator of protein kinase C, enhanced the contractions induced by 0.3 μmm Ca2+.
It was concluded that LTD4 acts on both the endothelium and on the smooth muscle cells of the guinea‐pig basilar artery. It stimulates the release of endothelium‐derived relaxing factor (EDRF) which tends to inhibit the LTD4‐induced contraction. It also interacts with receptors on the smooth muscle and produces a contraction as a result of an increase in both voltage‐dependent and receptor‐activated Ca2 influx and, in part, the release of Ca2 + from cellular storage sites.
Na/Ca exchange and tension development in vascular smooth muscle: effect of amiloride
Authors: Bova Sergio , Cargnelli Gabriella , Luciani Sisto 
Published: July 2012

The potassium‐sparing diuretic, amiloride, has been shown to inhibit the Na/Ca exchange system in various preparations. The effects of this drug have been investigated on the contractions of guinea‐pig aortic strips elicited by reduction of external K, by addition of ouabain and by removal of external Na.
Amiloride (5 × 10−6 m‐5 × 10−4 m) inhibited the mechanical responses when it was added before giving the stimulus for contractions, but was not effective in relaxing the contracted strips. The drug shifted to the right the dose‐response curve for Ca in low K solution.
The calcium antagonist diltiazem had no effect on the ouabain‐, low K‐ and Na‐free‐induced contractions.
Amiloride decreased the rate of relaxation of aortic strips induced by removal of the low K solution.
The pattern of amiloride action on ouabain‐, low K‐ and Na‐free‐induced contractions suggests that the drug interferes with Ca influx. The effect of amiloride on the relaxation rate of low K‐ contracted aortic strips is consistent with an interference with Ca efflux.
It is suggested that amiloride prevents Ca fluxes through the Na/Ca exchange system of guinea‐pig aortic strips.
Studies on the effects of viprostol in isolated small blood vessels and thoracic aorta of the rat
Authors: Lai Fong M. , Tanikella Tarak , Cobuzzi Agnes , Cervoni Peter 
Published: July 2012

The effects of viprostol, prostaglandin E2 (PGE2) and nitroglycerin were studied in basilar artery, small mesenteric artery and the vein parallel to it as well as thoracic aorta of the rat.
In KCl‐contracted basilar artery, viprostol produced a concentration‐related biphasic response, contraction at concentrations < 3 × 10−6 m and relaxation at concentrations >3 × 10−6 m. PGE2 produced a concentration‐related contraction while nitroglycerin produced a concentration‐related relaxation.
In KCl‐contracted small mesenteric artery, viprostol produced a biphasic response which was similar to that in the basilar artery. PGE2 produced a contraction and nitroglycerin produced relaxation in a concentration‐dependent manner.
In KCl‐contracted small mesenteric vein, in contrast to basilar and mesenteric artery, viprostol produced only a concentration‐related relaxation in the range of 1 × 10−6 to 1 × 10−4 m. PGE2 produced a contraction and nitroglycerin produced a concentration‐related relaxation.
In KCl‐contracted thoracic aorta, PGE2 produced a biphasic response, relaxation at concentrations < 3 × 10−7 m and a concentration‐related contraction at concentrations > 3 × 10−7 m. Viprostol only produced a concentration‐related contraction at concentrations >1 × 10−6 m, which was significantly less in magnitude than the contraction produced by PGE2. Nitroglycerin produced a concentration‐related relaxation as seen in the small vessels.
In conclusion, the present data demonstrate that viprostol is a vasorelaxant agent which effectively dilates KCl‐contracted basilar, small mesenteric artery and vein, but not the thoracic aorta of rat. The potent antihypertensive action of viprostol is probably due to its relaxant effect on the small arteries and veins but not on the large conduit artery.