bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensin II does not inhibit vagally‐induced bradycardia or gastric contractions in the anaesthetized ferret
Authors: Andrews P.L.R. , Dutia M.B. , Harris P.J. 
Published: July 2012

The effects of angiotensin II (AII) and the analogue Sar1‐Leu8‐angiotensin II on the changes in heart rate and gastric pressure induced by vagal stimulation were investigated in the urethane‐anaesthetized ferret.
AII at high doses (500 ng kg−1 i.v.) increased blood pressure and decreased gastric pressure whereas Sar1‐Leu8‐AII at the same dose had a much smaller effect on blood pressure and no effect on gastric pressure.
Intravenous injections or infusions of AII or its analogue did not alter the effect of vagal stimulation on heart rate or gastric motility. Our results do not provide support for the proposal that AII modulates parasympathetic activity at peripheral sites (Potter, 1982a, b).
Solubilization and characterization of guanine nucleotide‐sensitive muscarinic agonist binding sites from rat myocardium
Authors: Berrie Christopher P. , Birdsall Nigel J.M. , Hulme Edward C. , Keen Mary , Stockton Jane M. 
Published: July 2012

Muscarinic receptors from rat myocardial membranes may be solubilized by digitonin in good yield at low temperatures in the presence of Mg2+.
Under these conditions, up to 60% of the soluble receptors show high affinity binding for the potent agonist [3H]‐oxotremorine‐M (KA = 109M−1), which is inhibited by 5′‐guanylylimido‐diphosphate.
The muscarinic binding site labelled with [3H]‐oxotremorine‐M has a higher sedimentation coefficient (13.4 s) than sites labelled with a 3H antagonist in the presence of guanylylimidodiphosphate (11.6 s) and probably represents a complex between the ligand binding subunit of the receptor and a guanine nucleotide binding protein.
Effects of some depressant drugs on synaptic responses to glutamate at the crayfish neuromuscular junction
Authors: Wachtel Ruth E. 
Published: July 2012

Excitatory junction currents produced by glutamate were recorded with an extracellular electrode at the neuromuscular junction of the crayfish.
Pentobarbitone, phenobarbitone, diazepam, chlordiazepoxide and procaine had only minimal effects on current decay at concentrations which are highly effective in other preparations. The glutamate synapse in the crayfish appears relatively resistant to these drugs.
In contrast, ether and halothane increased the rate of decay of the currents at concentrations which are comparable to those occurring during anaesthesia.
Responses of human, monkey and dog coronary arteries in vitro to carbocyclic thromboxane A2 and vasodilators
Authors: Toda Noboru 
Published: July 2012

Carbocyclic thromboxane A2 (cTxA2), a stable analogue of TxA2, and prostaglandin (PG) F2α contracted helical strips of human, monkey and dog coronary arteries in a concentration‐dependent manner. Apparent ED50 values for cTxA2 were markedly less (1/58 in humans, 1/373 in monkeys and 1/397 in dogs) than those for PGF2α; maximum contractions induced by cTxA2 and PGF2α relative to those induced by 30 mM K+ were approximately identical in the human and monkey arteries.
PGI2 caused a concentration‐related relaxation in human and dog coronary arteries maximally precontracted with cTxA2 and in human, monkey and dog coronary arteries partially precontracted with PGF2α. The relaxation response was greatest in the dog arteries and least in the monkey arteries.
Contractions induced by cTxA2 or PGF2α and relaxations induced by PGI2 were selectively antagonized by treatment with diphloretin phosphate.
Human coronary artery strips contracted with cTxA2 responded to nitroglycerine with a rapid, transient relaxation and to verapamil with a slowly‐developing, persistent relaxation, as did monkey and dog coronary artery strips.
Thromboxane (Tx) A2 appears to be one of the most potent endogenous vasoconstrictors in human coronary arteries, if cTxA2 acts on TxA2 receptors. It is suggested that PGI2, nitroglycerine and verapamil are effective vasodilators in human conduit coronary arteries maximally contracted with cTxA2, although the extent and the duration of vasodilatation induced by these agents were quite different.
Cardiovascular studies with SK&F 93319, an antagonist of histamine at both H1‐ and H2‐receptors
Authors: Harvey Carol A. , Owen D.A.A. 
Published: July 2012

Cardiovascular studies have been made in anaesthetized cats with SK&F 93319, an antagonist of histamine at both H1‐ and H2‐receptors.
SK&F 93319, 8 × 10−8 and 4 × 10−7 mol kg−1 min−1 antagonized depressor responses to injections of histamine and the maximum displacement of histamine dose‐response curves exceeded that which can be obtained with either an H1‐receptor antagonist or an H2‐receptor antagonist alone.
SK&F 93319, 8 × 10−8 and 4 × 10−7 mol kg−1 min−1, also caused dose‐dependent antagonism of histamine‐induced falls in blood pressure and total peripheral resistance during intravenous infusions of histamine.
SK&F 93319 inhibited depressor responses to intravenous injections of 2‐(2‐aminoethyl)pyridine, dimaprit and impromidine. The displacement of the 2‐(2‐aminoethyl)pyridine dose‐response curve was similar to the displacement of histamine dose‐response curves. SK&F 93319 caused greater displacement of dimaprit or impromidine dose‐response curves than of histamine or 2‐(2‐aminoethyl)pyridine dose‐response curves.
SK&F 93319 was an effective antagonist of histamine, 2‐(2‐aminoethyl)pyridine or dimaprit‐induced vasodilatation in femoral and gastric vasculature.
SK&F 93319 has been shown to be an effective antagonist of vascular responses to histamine in anaesthetized cats. SK&F 93319 appeared to be more effective as an H2‐receptor antagonist than as an H1‐receptor antagonist in these vascular studies.
A new canine model of endotoxin shock
Authors: Evans S.F. , Hinds C.J. , Varley J.G. 
Published: July 2012

A new canine model of endotoxin shock has been developed in which spontaneous recovery of cardiovascular function is largely prevented, the haemodynamic effects of anaesthesia are minimized and intravascular volume replacement is given.
This model has been evaluated using two groups of five adult mongrel dogs anaesthetized with α‐chloralose and breathing spontaneously. Animals in one group were anaesthetized, instrumented and given Escherichia coli (E. coli) endotoxin intravenously, whilst those in the control group were subjected only to anaesthesia and instrumentation.
E. coli endotoxin was given to dogs in the shock group as a bolus dose of 5 mg kg−1 followed by a continuous infusion at 2 mg kg−1 h−1. This produced immediate, severe, cardiovascular depression, with precipitous falls in mean arterial pressure (MAP), cardiac index (CI), stroke index (SI) and left ventricular (LV) dp/dt max. There were associated increases in systemic and pulmonary vascular resistances. Arterio‐venous oxygen content difference (C(a‐v)O2) increased after induction of shock, and animals developed a progressive metabolic acidosis. Increasing haemoconcentration occurred, as evidenced by a rising haematocrit (PCV). Hypovolemia was reflected by a concurrent fall in pulmonary capillary wedge pressure (PCWP).
One hour after induction of shock, intravascular volume replacement was given in the form of a colloidal gelatin solution, as a bolus dose of 10 ml kg−1, followed by a continuous infusion at 10 ml kg−1 h−1. Volume replacement reversed haemoconcentration, restored PCWP and produced some haemodynamic improvement, although in general, severe cardiovascular depression persisted throughout a three hour observation period.
This severe endotoxin shock model has proved to be stable, reproducible and economical. It provides a useful preliminary test for new methods of treatment in hypodynamic endotoxin shock, as well as allowing investigation of acute metabolic and physiological changes.
Effects of intravascular volume expansion on the cardiovascular response to naloxone in a canine model of severe endotoxin shock
Authors: Evans S. F. , Hinds C.J. , Varley J.G. 
Published: July 2012

The specific opiate receptor antagonist, naloxone, can produce haemodynamic improvement and increased survival in experimental shock. The efficacy of naloxone therapy in a canine model of endotoxin shock has been evaluated both with and without intravascular volume replacement.
Animals were anaesthetized with α‐chloralose and allowed to breathe spontaneously. A large bolus dose of endotoxin was followed by a continuous infusion, and treatment was instituted one hour after the endotoxin bolus.
In the absence of volume replacement, naloxone caused only limited and transient increases in mean arterial pressure (MAP) and left ventricular (LV) dp/dt max, with little effect on cardiac index (CI). Total peripheral resistance index (TPRI) tended to rise in both control and naloxone‐treated dogs.
In volume‐replaced animals, naloxone produced substantial and sustained increases in the MAP and LV dp/dt max with an associated rise in the CI. TPRI rose initially in this series and then fell progressively. Further analysis of the improvements in the CI showed an increase in stroke index with a tendency for heart rate to fall.
These findings suggest a myocardial action of naloxone in endotoxin shock, which is augmented by volume replacement. An initial, transient vasoconstrictor effect cannot, however, be excluded. Further work is required to determine the mechanism of the effects described.
α2‐Adrenoceptor agonists potentiate responses mediated by α1‐adrenoceptors in the cat nictitating membrane
Authors: Shepperson N.B. 
Published: July 2012

α1 but not α2‐adrenoceptors mediate contractions of the cat nictitating membrane.
The contractions of this tissue evoked by α1‐adrenoceptor agonists, but not those evoked by angiotensin II, are potentiated by pre‐dosing with α2‐adrenoceptor agonists.
This potentiation is reversed by the α2‐adrenoceptor antagonist, WY 2639.
Pressor responses evoked by α1‐adrenoceptor agonists or angiotensin II were not affected by α2‐adrenoceptor agonists.
Contractions of the nictitating membrane evoked by noradrenaline were reduced by pretreatment with WY 2639.
These results suggest that in some tissues the role of α2‐ adrenoceptors may be to modulate responses to α1‐adrenoceptors, rather than to evoke a discrete response themselves.
Hydrostatic pressure modifies the action of octanol and atropine on frog endplate conductance
Authors: Ashford M.L.J. , Macdonald A.G. , Wann K.T. 
Published: July 2012

The effects of octanol, ethanol and atropine were examined on the time course of decay (τD) of miniature endplate currents (m.e.p.cs) in the frog neuromuscular junction at normal and high pressure.
Octanol (25–100 μM) decreased reversibly the τD of m.e.p.cs in a dose‐dependent manner, 100 μM reducing τD to 0.39 of the control value. Higher concentrations (200–500 μM) additionally depressed the amplitude of m.e.p.cs.
Hydrostatic pressure (3.19 and 5.25 MPa) reduced the τD of octanol (25–100 μM)‐shortened m.e.p.cs. Thus 3.19 MPa and 5.25 MPa reduced the τD in the presence of 100 μM octanol to 0.75 and 0.78 of the octanol treated values. This effect was not completely reversed on decompression. The m.e.p.c. amplitude is reversibly decreased by pressure in the presence of octanol.
Hydrostatic pressure (3.19–15.55 MPa) did not modify the effect of ethanol on τD. At 10.40 and 15.55 MPa the τD was increased equally in the absence or presence of ethanol.
Atropine (60 μM) reduced the τD and amplitude of m.e.p.cs to 0.33 and 0.63 of the control values. These effects were compeletely reversible. Hydrostatic pressure (3.19 and 5.25 MPa) reduced the τD of atropine‐shortened m.e.p.cs to 0.82 and 0.77 of the atropine‐treated values respectively. This effect was not completely reversed on decompression. Hydrostatic pressure also reversibly depressed the amplitude of atropine‐treated m.e.p.cs.
The implications of these drug‐hydrostatic pressure interactions are discussed.
Lack of effect of leukotriene D4 on Ca‐uptake in airway smooth muscle
Authors: Raeburn David , Rodger Ian W. 
Published: July 2012

The effects of verapamil on leukotriene D4 (LTD4)‐ and KCl‐induced contractions and 45Ca‐uptake were examined in guinea‐pig isolated tracheal smooth muscle.
Both LTD4 (0.1 to 200 nmol l−1) and KCl (8 to 125 mmol l−1) produced concentration‐dependent increases in tension in the tracheal preparations.
Verapamil (1 μmol l−1) inhibited the tension responses induced by both LTD4 and KCl.
LTD4 failed to increase the lanthanum‐resistant Ca content of tracheal smooth muscle at either low (EC25; 3 nmol l−1) or high (EC90; 50 nmol l−1) concentrations. Verapamil did not modify this result.
KCl (90 mmol l−1) increased the lanthanum‐resistant Ca content of the smooth muscle by approximately 60% over basal levels. This effect was completely inhibited by verapamil (1 μmol l1).
It is concluded that in this tissue, LTD4 utilizes principally an intracellular source of Ca2+ to initiate contraction whereas KCl is dependent upon the uptake of Ca2+ from the extracellular compartment. It is suggested that the inhibitory effects of verapamil may reflect an intracellular mechanism of action directed against Ca2+ release initiated by LTD4.
Transmitter release modulated by α‐adrenoceptor antagonists in the rabbit mesenteric artery: a comparison between noradrenaline outflow and electrical activity
Authors: Mishima Shuichi , Miyahara Hiroko , Suzuki Hikaru 
Published: July 2012

Effects of α‐adrenoceptor blockers (prazosin, yohimbine, phentolamine and phenoxybenzamine) on the outflow of noradrenaline (NA) and 3,4‐dihydroxyphenylglycol (DOPEG) during perivascular nerve stimulation were observed in relation to electrical events in the rabbit mesenteric artery.
Cocaine or imipramine increased the NA outflow and reduced the DOPEG outflow induced by nerve stimulation. In the absence of stimulation, cocaine and imipramine did not significantly modify the NA and DOPEG outflows.
The α‐adrenoceptor blockers we used enhanced the NA and DOPEG outflow during nerve stimulation, in a dose‐dependent manner; the potency of the enhancement was higher for phentolamine and phenoxybenzamine than for prazosin and yohimbine. Higher concentrations (10−5 M) of yohimbine reduced the NA and DOPEG outflows induced by nerve stimulation.
Prazosin increased the DOPEG outflow in the absence of stimulation, and this effect was not inhibited by pretreatment with cocaine.
Guanethidine increased the NA and DOPEG outflow in the absence of stimulation, and the NA outflow was reduced during nerve stimulation. These effects of guanethidine were prevented by pretreatment with cocaine or imipramine.
Perivascular nerve stimulation evoked excitatory junction potentials (e.j.ps) and with high frequency stimulation, slow depolarization and spike potentials.
Application of phentolamine, phenoxybenzamine or yohimbine enhanced, and of prazosin had no effect, on the amplitude of the e.j.p. Spike potentials were not affected by these α‐adrenoceptor blockers. Slow depolarization ceased in the presence of prazosin, phentolamine or phenoxybenzamine, and was slightly inhibited by yohimbine. Guanethidine blocked all of these electrical responses induced by perivascular nerve stimulation.
Application of prazosin, phentolamine or phenoxybenzamine did not alter the resting membrane potential of the smooth muscle cells. Depolarizations of smooth muscle membrane produced by exogenously applied NA were inhibited by prazosin, phentolamine or phenoxybenzamine. Yohimbine itself depolarized the membrane and the inhibitory effects on the NA‐induced depolarization were weaker.
We conclude that the smooth muscle membrane of the rabbit mesenteric artery possesses α1‐adrenoceptors. Increase in NA outflow by α‐adrenoceptor antagonists during nerve stimulation was not always consistent with increase in e.j.p. amplitude, presumably due to involvement of actions other than α‐adrenoceptor blockade with each of these antagonists.
Photodynamic effects of erythrosine on the smooth muscle cells of guinea‐pig taenia coli
Authors: Matthews E.K. , Mesler D.E. 
Published: July 2012

Photon activation of the halogenated fluorescein derivative erythrosine caused a marked calcium‐dependent contraction of the smooth muscle cells of the guinea‐pig taenia coli superfused in vitro. Neither high intensity illumination alone (up to 5 × 104 lux) nor erythrosine alone (up to 2 × 10−4 M) altered the tone of the taenia or its ability to respond to carbachol (5 × 10−5M); photo‐irradiation of erythrosine before tissue contact was also ineffective.
The magnitude of the photodynamic contraction was dependent upon the concentration of erythrosine, the intensity and wavelength of the incident light, and the presence of oxygen; indirect effects via neurotransmitter release or cyclo‐oxygenase activation were specifically excluded.
The photodynamic response was blocked by zero‐[Ca]o and addition of EGTA (1 mM) but not by omission of [Mg]o or a decrease in [Cl]o or [Na]o. D600 (methoxyverapamil) 10−5 M, or a ten fold increase in [Mg]o, to 11.3 mM, partly inhibited the photodynamic contraction at low, but not high, light intensities.
These observations are consistent with the following sequence of events: (i) photo‐activation of the erythrosine molecule, (ii) the generation of highly reactive singlet oxygen, (iii) local peroxidation of cell membrane proteolipid, (iv) increased membrane permeability to Ca2+, (v) the influx of Ca2+ and, (vi) muscle contraction.
It is concluded that the photodynamic action of erythrosine presents a novel method for modulation of membrane calcium permeability, and hence [Ca]i, not only in smooth muscle but possibly in other cells as well, e.g., secretory, epithelial and myocardial cells.
Opioid receptor types on adrenergic nerve terminals of rabbit ear artery
Authors: Fukuda Hiroshi , Hosoki Eiji , Ishida Yukio , Moritoki Hideki 
Published: July 2012

Methionine enkephalin, leucine enkephalin, [D‐Ala2, D‐Leu5] enkephalin, α‐neoendorphin, β‐endorphin, dynorphin (1–13) and ethylketocyclazocine inhibited the contractions of rabbit ear artery ring segments elicited by transmural nerve stimulation at 8 Hz.
Ethylketocyclazocine, dynorphin (1–13) and leucine enkephalin produced partial inhibition, their apparent intrinsic activities (α) being 0.57, 0.75 and 0.66, respectively.
Morphine and normorphine, which are agonists at μ‐receptors, did not inhibit the response of the artery.
Naloxone antagonized the actions of opioids and ethylketocyclazocine, and was more effective against methionine enkephalin, leucine enkephalin and [D‐Ala2, D‐Leu5] enkephalin than against α‐neoendorphin, ethylketocyclazocine and dynorphin (1–13). The pA2 values of naloxone against so‐called δ‐agonists were approx. 8.5, and against so‐called k‐agonists were approx. 7.7.
The supposed k‐antagonist, Mr 2266, was more effective than naloxone in antagonizing the actions of α‐neoendorphin, and the k‐agonists dynorphin (1–13) and ethylketocyclazocine. The pA2 values of Mr 2266 against k‐agonists were 8.5–9.0, and against δ‐agonists were 7.8 or less.
The opioid peptides and opioids tested did not cause dilatation of the artery previously contracted with histamine.
These results suggest that the opioid peptides and ethylketocyclazocine acted on opioid receptors at adrenergic nerve terminals in the ear artery.
The opioid receptors appear to be of the δ‐ and k‐types, not the μ‐type.
Further analysis of anomalous pKB values for histamine H2‐receptor antagonists on the mouse isolated stomach assay
Authors: Black J.W. , Leff P. , Shankley N.P. 
Published: July 2012

Agonist‐antagonist interactions at histamine receptors have been re‐examined using improved techniques, on the mouse isolated, lumen‐perfused, stomach gastric acid assay.
Using histamine as agonist, pKB values have been estimated for burimamide, metiamide, cimetidine, ranitidine, oxmetidine and famotidine on both the gastric and guinea‐pig isolated right atrium assays. With the exception of oxmetidine on the atrial assay, these compounds behaved as competitive antagonists on both assays.
Oxmetidine significantly depressed basal rate on the atrial assay and the Schild plot slope parameter (0.81) was significantly less than one.
The pKB values estimated on the gastric assay were lower than those on the atrial assay. However, the difference between the values on the gastric and atrial assays was not constant. The difference between the two assays for famotidine was not significant.
We conclude that the apparent varying selectivity of the antagonists for gastric and atrial histamine H2‐receptors may be explained by the differential loss of antagonists into the gastric secretion from the receptor compartment and that there is no need to postulate heterogeneity of histamine H2‐receptors.
Pharmacological analysis of muscarinic receptors coupled to oxyntic cell secretion in the mouse stomach
Authors: Black J.W. , Shankley N.P. 
Published: July 2012

In the light of recent attempts to subclassify muscarinic receptors, agonist‐antagonist interactions at muscarinic receptors have been re‐examined using improved techniques, on the mouse, isolated, lumen‐perfused stomach gastric acid assay.
Using 5‐methylfurmethide as the muscarinic agonist, the pKB estimated for atropine was significantly lower on the stomach assay (7.78) than on the guinea‐pig trachea (8.93). However pKB values for N‐methylatropine, the quaternary ammonium derivative of atropine, at concentrations producing dose‐ratios above 20 on the stomach assay (pKB = 9.67), and over the full concentration range studied on the trachea (pKB = 9.69) were not significantly different.
The deviation from simple competitive behaviour at low dose‐ratios with N‐methylatropine in the stomach assay is consistent with the effects of a saturable uptake mechanism for quaternary ammonium compounds.
The pKB values for pirenzepine on the stomach (6.67) and the trachea (6.87) were not significantly different suggesting that pirenzepine behaves more like N‐methylatropine in terms of expressed affinity.
We conclude that the oxyntic cell muscarinic receptors are homogeneous with those in the guinea‐pig trachea. An initial exploration suggests that there is a relationship between the lipophilicity (log P) of the antagonists and the degree of apparent underestimation of antagonist affinity in the stomach assay. This supports the hypothesis that the underestimation of antagonist affinity is due to the loss of antagonist into the gastric secretion from the receptor compartment. Apparently, relatively selective inhibition of acid secretion, compared to atropine, could be explained without the need to postulate heterogeneity of muscarinic receptor populations.
The effect of prednisolone and ketotifen on the antigen‐induced bronchoconstriction and mediator release in rat isolated lungs
Authors: Ottenhof Maria , Ufkes Jan G.R. , Van Rooij Hans H. 
Published: July 2012

Using a new method for inducing IgE‐mediated, systemic anaphylaxis in the rat both prednisolone and ketotifen had been shown previously to be effective in suppressing the bronchial anaphylaxis in vivo. In order to study the mode of action underlying their bronchoprotective effect, both agents were also tested on the antigen‐induced bronchoconstriction in rat isolated lungs in relation to the mediator release in the lung‐effluent.
The presence of histamine, 5‐hydroxytryptamine (5‐HT) and SRS‐A could be detected biologically in the lung‐effluent during bronchoconstriction. Histamine and 5‐HT were determined quantitatively by means of h.p.l.c. with fluorimetric detection, whereas SRS‐A was determined using the guinea‐pig ileum in a cascade set‐up.
Although both prednisolone and ketotifen inhibited the antigen‐induced bronchoconstriction effectively, it appeared that only prednisolone suppressed the release of histamine, 5‐HT and SRS‐A in the lung‐effluent significantly, whereas ketotifen had no effect.
On account of these data it is suggested that the bronchoprotective effect of prednisolone is mainly based on inhibition of the release of the mediators involved, whereas the effect of ketotifen may be based on receptor antagonism.