bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of morphine on catecholamine release and arrhythmias evoked by myocardial ischaemia in rats
Authors: Addicks Klaus , Hirche Hansjürgen , McDonald Fiona M. , Polwin Wolfgang 
Published: July 2012

The effects of morphine (10 mg kg01 i.p.) on haemodynamics, arrhythmias and plasma and myocardial catecholamines (CA) were studied after coronary artery occlusion in anaesthetized rats. Myocardial intraneuronal CA were assessed histofluorimetrically and CA concentrations measured by high performance liquid chromatography.
Morphine increased blood pressure, presumably due to higher plasma noradrenaline (NA) concentrations found in morphine‐treated rats.
Morphine increased the area of catecholamine‐containing fluorescing neurones in the myocardium (as a percentage of total field area) 60 min after sham‐operation (0.87 ± 0.07%) or occlusion (0.57 ± 0.05%) compared to untreated animals (0.67 ± 0.06 and 0.38 ± 0.03% respectively). Tissue NA content was not significantly affected by coronary occlusion and/or morphine within the first 60 min.
Morphine had no effect on ischaemia‐induced arrhythmias.
Whether the higher intraneuronal NA content following morphine resulted from reduced central sympathetic outflow to the heart, presynaptic inhibition of NA release, or increased uptake due to higher plasma concentrations is unclear. Ischaemia‐induced local NA release appears independent of these mechanisms, as it was unaffected by morphine.
(5Z)‐carbacyclin discriminates between prostacyclin‐receptors coupled to adenylate cyclase in vascular smooth muscle and platelets
Authors: Corsini A. , Folco G.C. , Fumagalli R. , Nicosia S. , Noe M.A. , Oliva D. 
Published: July 2012

(5E)‐ and (5Z)‐carbacyclin are prostacyclin (PGI2) analogues endowed with antiaggregating and vasodilator properties, which stimulate adenylate cyclase activity in membranes from human platelets and cultured myocytes from rabbit mesenteric artery.
In platelets they display the same efficacy as prostaglandin E1 (PGE1), and hence PGI2, both as activators of adenylate cyclase and as inhibitors of aggregation.
In contrast, in vascular smooth muscle cells (5Z)‐carbacyclin fails to produce the same degree of stimulation of the enzyme as PGI2, (5E)‐carbacyclin and PGE, nor does it induce the maximal relaxation of the mesenteric artery as do the other prostaglandins.
(5Z)‐carbacyclin is also able to antagonize the activation of adenylate cyclase and the relaxation elicited by PGE1 or PGI2 in the mesenteric artery, and therefore it displays partial agonist properties in these cells.
We conclude that the receptors for PGI2 coupled to adenylate cyclase in platelets and vascular smooth muscle cells are different from each other, because (5Z)‐carbacyclin can discriminate between them, being a partial agonist at myocyte but not at platelet level.
Control of alveolar surfactant in rats at rest and during prolonged hyperpnoea: pharmacological evidence for two tissue pools of surfactant
Authors: Barr Heather A. , Nicholas Terence E. , Power John H.T. 
Published: July 2012

Propranolol, atropine and indomethacin (i.p.) affect neither the amount (PLalv), nor the specific activity (PLalvsp.act.) of alveolar surfactant‐type phospholipids lavaged from the lungs of unanaesthetized rats, either at rest or made hyperpnoeic for 24 h with 5%CO2/13%O2/82%N2.
Whereas salbutamol (280 μg kg−1 body weight, i.p.) consistently increased PLalv and PLalvsp.act., pilocarpine (1.5, 3, 10 and 50 mg kg−1, i.p.) and labetalol (1 and 5 mg kg−1, i.p.) had no effect. The dose of pilocarpine reported by others to release surfactant (150 mg kg−1) induced marked salivation, diarrhoea, chromodacryorrhoea and a three‐fold increase in tidal volume.
In the isolated perfused lung of the rat, salbutamol (1.5 μm) consistently increased PLalvsp.act, whereas pilocarpine (0.1 and 1 μM) had no effect on these variables.
In the isolated perfused lung, the maximum amount of surfactant that could be released by salbutamol (0.5 mM) was smaller than that which could be released in response to an increase in tidal volume (peak inflation pressure 28 cmH2O).
When the concentration of salbutamol in the isolated perfused lung was adjusted to produce the same increase in PLalv as did a single simulated deep breath, the PLalvsp.act was significantly increased by salbutamol, but not by the simulated deep breath.
We conclude, that neither the autonomic nervous system nor the prostaglandin system is essential for the release of surfactant at rest or during hyperpnoea. Furthermore, we suggest that two pools of surfactant, with different release mechanisms, exist in lung tissue.
Studies on the anti‐vasoconstrictor activity of BRL 34915 in spontaneously hypertensive rats; a comparison with nifedipine
Authors: Buckingham Robin E. 
Published: July 2012

The blood pressure lowering and anti‐vasoconstrictor effects of BRL 34915 and nifedipine were compared in female spontaneously hypertensive rats (SHR).
In conscious SHR, intravenous injection of BRL 34915 (0.1, 0.3 mg kg−1) produced rapid, dose‐related falls in mean arterial pressure of greater than 3 h duration. Nifedipine, at the same intravenous dose levels, also evoked rapid anti‐hypertensive effects, though these responses were of lesser magnitude and duration than those observed for BRL 34915.
In anaesthetized, ganglion‐blocked SHR, BRL 34915 (0.1, 0.3 mg kg−1 i.v.) dose‐dependently antagonized the pressor responses to incremental intravenous influsions of noradrenaline (3.8–28.5 ng min−1) or phenylephrine (120–907 ng min−1) but did not inhibit pressor responses to incremental infusions of methoxamine (0.47‐3.63 μh min−1), angiotensin II (7.0–52.9 ng min−1) or vasopressin (0.27‐2.0 mu min−1).
In anaesthetized, ganglion‐blocked SHR, nifedipine (0.1, 0.3 mg kg−1 i.v.) antagonized the pressor responses to each of the infused vasoconstrictor agents, being most effective against responses to noradrenaline or angiotensin II.
In pithed SHR, both BRL 34915 and nifedipine (each at 0.3 mg kg−1 i.v.) reduced the basal blood pressure level and produced marked inhibition of frequency‐dependent pressor responses evoked by electrical stimulation of the spinal cord sympathetic outflow (0.25‐4.0 Hz). Restoration of the basal diastolic blood pressure to within the control range, using a continuous intravenous infusion of vasopressin (0.98 mu min−1), prevented the inhibitory effect of BRL 34915. In the case of nifedipine, however, even raising the basal blood pressure to a level exceeding that recorded in control rats (with vasopressin, 2.0 mu min−1), did not reverse the inhibitory effect of the drug on frequency‐dependent pressor responses.
It is concluded that the anti‐hypertensive properties of BRL 34915 in SHR are probably unrelated to an anti‐vasoconstrictor action. In contrast, it is suggested that the broadly‐based anti‐vasoconstrictor properties of nifedipine may contribute substantially to the anti‐hypertensive properties of this drug.
A study of the action of amlodipine on adrenergically regulated sodium handling by the kidney in normotensive and hypertensive rats
Authors: Johns Edward J. 
Published: July 2012

An investigation was undertaken to examine the effect of calcium channel blockade, induced by amlodipine, on the ability of the renal sympathetic nerves to cause an antidiuresis and anti‐natriuresis in normotensive Sprague Dawley and spontaneously hypertensive rats anaesthetized with pentobarbitone.
Low frequency renal nerve stimulation in normotensive rats, which did not change renal blood flow, caused a 15% reduction in glomerular filtration rate and was associated with falls in urine flow of 37%, absolute sodium excretion of 47%, and fractional sodium excretion of 38%. The magnitude of these renal excretory changes was unaffected by prior administration of amlodipine at either 200 μg kg−1 plus 50 μg kg−1 h−1 or 400 μg kg−1 plus 100 μg kg−1 h−1. Amlodipine given in the higher dose, decreased basal levels of blood pressure and increased basal urine flow and sodium excretion.
In spontaneously hypertensive rats, renal nerve stimulation minimally affected renal haemodynamics but decreased urine flow, absolute and fractional sodium excretion by 29%, 31% and 24%, respectively.
Similar renal nerve stimulation in spontaneously hypertensive rats given amlodipine at 200 μg kg−1 plus 50 μg kg−1 h−1 or 400 μg kg−1 plus 100 μg kg−1 h−1 caused minimal changes in renal haemodynamics and in the excretion of water and sodium. The higher dose of drug resulted in decreased blood pressure and increased basal rates of urine flow and sodium excretion.
These data show that in spontaneously hypertensive rats but not normotensive rats, calcium channel blockade inhibited the ability of the renal nerves to stimulate the reabsorptive processes for sodium at the renal tubule. This indicated that in spontaneous hypertension the post‐receptor mechanisms had changed and become more dependent on the inward movement of calcium.
The effect of nedocromil sodium, sodium cromoglycate and codeine phosphate on citric acid‐induced cough in dogs
Authors: Jackson D.M. 
Published: July 2012

The effects of nedocromil sodium, sodium cromoglycate and codeine phosphate on citric acid‐induced cough have been studied in conscious tracheostomised dogs.
Nedocromil sodium (approximately 15 mg given as an aerosol) and codeine phosphate (5 mg kg−1, i.v.) significantly increased the time to the first cough when dogs were challenged with citric acid aerosol. The mean number of coughs in the initial period of coughing fell after treatment of dogs with nedocromil sodium or with codeine phosphate, but this reduction in mean cough number was not statistically significant.
Neither sodium cromoglycate (approximately 15 mg given as an aerosol) nor saline had significant effect on a citric acid challenge.
It is concluded that nedocromil sodium, but not sodium cromoglycate, possesses an anti‐tussive action that may result from inhibition of sensory nerve activity in the lung. Nedocromil sodium may prove useful in the treatment of unproductive cough in situations where the use of a centrally‐acting antitussive is undesirable.
5‐Hydroxytryptamine‐induced tachycardia in the pig: possible involvement of a new type of 5‐hydroxytryptamine receptor
Authors: Bom A.H. , Duncker D.J. , Saxena P.R. , Verdouw P.D. 
Published: July 2012

The mechanism of 5‐hydroxytryptamine (5‐HT)‐induced tachycardia is species‐dependent and is mediated directly or indirectly either by ‘5‐HT1‐like’ (cat), 5‐HT2 (rat, dog) or 5‐HT3 (rabbit) receptors, or by an action similar to tyramine (guinea‐pig). The present investigation is devoted to the analysis of the positive chronotropic effect of 5‐HT in the pentobarbitone‐anaesthetized pig.
Intravenous bolus injections of 5‐HT (3, 10 and 30 μg kg−1) in pigs resulted in dose‐dependent increases in heart rate of 24 ± 2, 38 ± 3 and 51 ± 3 beats min−1, respectively (n = 39). Topical application of a high concentration of 5‐HT (150 μg kg−1 in 5 ml) on the right atrium was also followed by tachycardia (38 ± 6 beats min−1, n = 4).
A number of drugs which antagonize responses mediated by different 5‐HT receptors ‐ phenoxybenzamine, methiothepin, metergoline, methysergide and mesulergine (‘5‐HT1‐like’ and 5‐HT2 receptors), ketanserin, cyproheptadine, pizotifen and mianserin (5‐HT2 receptors), and MDL 72222 and ICS 205–930 (5‐HT3 receptors) — did not attenuate the chronotropic responses to 5‐HT.
The 5‐HT‐induced tachycardia was also not affected by antagonists at α‐ and β‐adrenoceptors, muscarinic, nicotinic, histamine and dopamine receptors, and calcium channels.
Selective inhibitors of 5‐HT‐uptake, indalpine and fluvoxamine, themselves increased porcine heart rate and facilitated 5‐HT‐induced tachycardia both in magnitude and in duration.
A number of putative selective agonists at ‘5‐HT1‐like’ receptors or their possible subtypes (5‐carboxamidotryptamine (5‐CT), 8‐hydroxy‐2‐(di‐N,N‐n‐propylamino) tetralin (8‐OH‐DPAT), BEA 1654 and RU 24969), or at 5‐HT3 receptors (2‐methyl‐5‐HT), elicited no or only a weak tachycardiac response in the pig. RU 24969, but not 8‐OH‐DPAT, seemed to potentiate the responses to 5‐HT, whereas 5‐CT slightly inhibited these responses.
It was concluded that the tachycardia induced by 5‐HT in the pig does not involve the receptors for some common neurotransmitter substances but may be mediated by a new 5‐HT receptor type that is clearly different from ‘5‐HT1 ‐like’, 5‐HT2 or 5‐HT3 receptors.
The effects of the novel anti‐anginal compound RS 43285 on myocardial conduction in the anaesthetized dog
Authors: Allely Maxine C. , Alps B.J. 
Published: July 2012

A pentobarbitone‐anaesthetized canine model of myocardial conduction was developed to evaluate drug effects on intra‐atrial (I‐A), intra‐ventricular (I‐V) and atrioventricular (A‐V) conduction parameters, both at rest and during electrical pacing of the right atrium or ventricle. Drug effects on the ability of the sino‐atrial (SA) node to re‐establish sinus rhythm on switching off electrical pacing were also considered. The effects of the novel anti‐anginal compound RS 43285‐193 ((±)‐N‐(2,6‐dimethylphenyl)‐4[2‐hydroxy‐3‐(2‐methoxyphenoxy)propyl]‐1‐piperazine acetamide dihydrochloride) were compared to those of the standard anti‐anginal compounds nicardipine, nifedipine and verapamil.
In the dose range 15–7000 μg kg−1, RS 43285 had no significant effects on I‐A, I‐V or A‐V conduction either at rest or during electrical pacing and did not affect the re‐establishment of sinus rhythm.
Nicardipine had no effects on conduction parameters at resting heart rate. There were no effects on I‐A or I‐V conduction on electrical pacing but A‐V conduction was increased at 200–500 μg kg−1 (with a 2:1 A‐V conduction block in two out of six dogs); this was accompanied by a prolongation of the interval to reversion of sinus rhythm.
Nifedipine had no significant effects on I‐A or I‐V conduction but significantly prolonged A‐V conduction at 1000 μg kg−1 and this dose also increased the interval to SA node recovery.
Verapamil did not effect I‐A or I‐V conduction. However, A‐V conduction was affected with a significant prolongation occurring at resting heart rate at 100–400 μg kg−1 and a 2:1 A‐V block in one dog at rest. During right atrial pacing verapamil significantly increased A‐V conduction at 50–400 μg kg−1. All dogs exhibited a 2:1 A‐V conduction block at the highest frequency at 400 μg kg−1.
Inhibitory regulation by co‐released peptides of catecholamine secretion by the canine adrenal medulla
Authors: Critchley J.A.J.H. , MacLean Margaret R. , Ungar A. 
Published: July 2012

We have stimulated the peripheral end of the cut left splanchnic nerve in anaesthetized dogs while collecting the venous effluent of the left adrenal gland for catecholamine estimation.
With low frequency stimulation the resting output of catecholamines was inhibited but at high frequencies it was augmented.
The inhibition of catecholamine output by low frequency stimulation was reversed by opiate antagonists (naloxone and nalmefene) but enhanced by angiotensin converting enzyme inhibitors (captopril and enalapril).
Comparison of the haemodynamic effects of the selective bradycardic agent UL‐FS 49, with those of propranolol during treadmill exercise in dogs
Authors: Krumpl G. , Winkler M. , Schneider W. , Raberger G. 
Published: July 2012

To clarify whether the bradycardic agent UL‐FS 49 exhibits a positive inotropic effect even in the absence of improvement in regional myocardial function of an underperfused myocardial area, this study was undertaken in dogs with unimpaired coronary flow.
We also investigated the haemodynamic and functional effects of the negative chronotropic and inotropic β‐adrenoceptor blocker propranolol.
UL‐FS 49 did not depress total or regional myocardial performance. Moreover, an increase in positive left ventricular dp/dt max at rest suggests a positive inotropic effect of UL‐FS 49.
Propranolol, in contrast to UL‐FS 49, led to a marked reduction in positive dp/dt max, stroke volume and systolic wall thickening at rest and during exercise. Additionally, propranolol decreased the exercise values of cardiac output, left ventricular work and left ventricular power to a far greater extent than UL‐FS 49.
In contrast to propranolol, the selective bradycardic agent UL‐FS 49 did not decrease total or regional ventricular performance and caused less reduction in cardiodynamic parameters during exercise.
These results suggest that patients with moderate coronary insufficiency or patients with coronary vessel disease and mild left ventricular failure may attain a higher exercise limit under selective bradycardia with UL‐FS 49 in comparison to that possible with a β‐adrenoceptor antagonist, such as propranolol.
The effect of anti‐inflammatory drugs on eicosanoid formation in a chronic model of inflammatory bowel disease in the rat
Authors: Boughton‐Smith N.K. , Wallace J.L. , Morris G.P. , Whittle B.J.R. 
Published: July 2012

The effects of anti‐inflammatory drugs on eicosanoid formation and colonic damage in a chronic model of inflammatory bowel disease (IBD) in the rat were investigated.
A single colonic instillation of the hapten, trinitrobenzene sulphonic acid (TNB) resulted in ulceration and inflammation which persisted for 3 weeks.
The macroscopic colonic damage, present 3 weeks after TNB, was correlated with an increase in immunoreactive 6‐keto‐prostaglandin F1α (6‐keto‐PGF1α) and leukotriene B4 (LTB4) synthesis by the rat colon.
Anti‐inflammatory drugs were administered 2 weeks after TNB, when there was substantial colonic damage, and continued for a week. The experimental drug BW755C inhibited the increased formation of 6‐keto‐PGF1α and LTB4 by the inflamed colon. Indomethacin and aspirin markedly inhibited prostanoid formation in both inflamed and control colon. Sulphasalazine or prednisolone also inhibited the formation of 6‐keto‐PGF1α but the effects were less marked.
None of the anti‐inflammatory drugs significantly reduced the colonic damage induced by TNB.
The results suggest that eicosanoids, including LTB4, have only a minor role in maintaining the chronic macroscopic damage induced in the rat colon by TNB. The role of such eicosanoids in the underlying infiltration and activity of inflammatory cells in this model of IBD, however, is not known.
Mustard oil excites but does not inhibit nociceptive dorsal horn neurones in the rat: a presumed effect on A‐delta fibres
Authors: Harris N.C. , Ryall R.W. 
Published: July 2012

Mustard oil was applied topically in concentrations of 10–20% to the excitatory and inhibitory nociceptive receptive fields in glabrous and hairy skin of the anaesthetized rat while recording the activity of nociceptive dorsal horn neurones. The noxious stimulus was radiant heat which is known to activate C‐fibres in glabrous and hairy skin.
Mustard oil had little effect when applied to glabrous skin and this was attributed to poor penetration of the skin.
Mustard oil excited cells in the dorsal horn which were excited by noxious heat in the receptive field on hairy skin.
Mustard oil excited cells in the dorsal horn which were inhibited by noxious heat in the receptive field on hairy skin.
Inhibitory effects of mustard oil were never seen, even when applied to receptive fields in which noxious heating caused inhibition.
The excitatory effects of mustard oil on cells inhibited by noxious heating of the skin are attributed to the reported activation of A‐delta fibres which probably masked any C‐fibre activation.
Vasodilator response to dopamine in the ferret pulmonary circulation
Authors: Gorman P. 
Published: July 2012

The isolated perfused lung of the ferret was used to study the effects of dopamine receptor agonists and antagonists. Under constant flow, a fall in pulmonary artery pressure reflects a vasodilator response. Since tone is normally low, agonists were given during hypoxic pulmonary vasoconstriction to enable detection of dilator responses.
Vasodilator responses were produced by bolus doses of dopamine over the range 0.1 to 5.0 μg kg−1, and by the selective DA1 agonist SK&F 38393 (1‐phenyl‐7,8‐dihydroxy‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine hydrochloride).
The dopamine response was blocked by low doses of the selective DA1‐antagonist SCH23390 (R‐(+)‐8‐chloro‐2,3,4,5‐tetrahydro‐3‐methyl‐5‐phenyl‐1H‐3‐benzazepine‐7‐ol maleate), and by sulpiride.
The vasodilator response to the relatively selective DA2‐agonist N,N‐di‐n‐propyl dopamine occurred only at high dose and was incompletely blocked by the selective DA2 antagonist domperidone at a cumulative dose of 10 mg kg−1.
Thus dopamine receptors of the DA1 type may mediate vasodilatation in the ferret pulmonary circulation, but no evidence was obtained for the existence of DA2‐receptors.
Actions of baclofen on components of the Ca‐current in rat and mouse DRG neurones in culture
Authors: Green K.A. , Cottrell G.A. 
Published: July 2012

Ca currents in rat and mouse sensory dorsal root ganglion (DRG) neurones were inhibited by concentrations of (—)‐baclofen as low as 1 μm. The proportion of neurones responding to baclofen was low (<20%), except in young cultures of neonate rat DRG neurones (3 days in culture), where 86% of the neurones were responsive.
Three types of unitary Ca currents were observed in the rat DRG neurones, corresponding to the T‐, N‐ and L‐type currents of chick DRG neurones.
Baclofen produced two types of response on whole‐cell currents of DRG neurones from both species. The first was on an early inactivating component of the Ca current. This early current was partially inactivated at a holding potential of −40 mV. It was also reduced during the second of a pair of depolarizing command pulses. The results suggest that this action of baclofen is due to an action on an N‐type component of the current. The second response to baclofen persisted throughout the command step and was not reduced during the second of a pair of command pulses, indicating that this effect is due to an action on the L‐type current.
Unitary or ensemble Ca currents recorded in cell‐attached patches, on neurones previously shown to respond to baclofen in whole‐cell clamp mode, were generally not inhibited by baclofen application external to the patch electrode. This indicates that a readily diffusible internal second messenger substance is probably not involved in coupling the GABAB receptor to the ion channels.
Effects of cholecystokinin and related peptides on neuronal activity in the ventromedial nucleus of the rat hypothalamus
Authors: Boden P. , Hill R.G. 
Published: July 2012

An investigation into the effects of cholecystokinin octapeptide (CCK‐8S) and its pentapeptide analogue, pentagastrin, on neurones located in ventromedial nuclei of rat hypothalamic slices maintained in vitro has been undertaken.
CCK‐8S (0.01‐1.0 μm) applied in the perfusion medium produced a concentration‐dependent increase in firing rate. This effect could be mimicked by pentagastrin and was selectively blocked by L‐364,718, a potent peripheral CCK receptor antagonist that has been shown to possess micro‐molar affinity for central CCK receptors.
Intracellular recordings from ventromedial nucleus neurones revealed two distinct populations with comparable resting membrane parameters but differing neuronal activity. One group fired tetrodotoxin (TTX)‐sensitive action potentials spontaneously at resting membrane potential whilst the second group fired action potentials only on injection of depolarizing current and were otherwise silent.
Application of CCK‐8S or pentagastrin to spontaneously active neurones produced a small depolarization concomitant with an increase in action potential firing rate but the peptides had no effect on membrane properties of ‘silent’ neurones.
These data suggest the existence of at least two populations of neurones in the ventromedial hypothalamus, only one of which is excited by CCK‐8S and pentagastrin.