bluuebunny/crossref_metadata_2025_split huggingface dataset:
CENTRAL CARDIOVASCULAR EFFECTS OF NARCOTIC ANALGESICS AND ENKEPHALINS IN RATS
Authors: BELLET M. , ELGHOZI J.L. , MEYER P. , PERNOLLET M.G. , SCHMITT H. 
Published: July 2012

The cardiovascular effects of morphine, fentanyl, [d‐Ala2]‐met‐enkephalinamide were analyzed after intracisternal injection in anaesthetized rats. Pao2 was measured as an index of respiratory function.
At low doses in spontaneously breathing rats, morphine, fentanyl and [d‐Ala2]‐met‐enkephalinamide induced a pressor response with slight tachycardia and no significant change in Pao2.
The pressor response appeared to be due to activation of opiate receptors and mediated through the sympathetic nervous system.
High doses of morphine and [d‐Ala2]‐met‐enkephalinamide induced a biphasic effect with a secondary hypotension associated with bradycardia in spontaneously breathing rats. A marked reduction in Pao2 was found during the depressor phase.
High doses of [d‐Ala2]‐met‐enkephalinamide produced only a pressor response in artificially‐ventilated rats with no signs of secondary hypotension.
Our data support the idea that morphinomimetic agents are centrally pressor at low doses in the rat. The respiratory depression observed with high doses may be the cause of hypotension.
THE INFLUENCE OF HORMONAL AND NEURONAL FACTORS ON RAT HEART ADRENOCEPTORS
Authors: KUNOS GEORGE , MUCCI LUCIA , O'REGAN SEANA 
Published: July 2012

The influence of hormonal and neuronal factors on adrenoceptors mediating increased cardiac force and rate of contraction were studied in rat isolated atria. The pharmacological properties of these receptors were deduced from the relative potencies of agonists and from the effects of selective α‐and β‐adrenoceptor antagonists. The numbers and affinities of α‐ and β‐adrenoceptors were also determined by radioligand binding to ventricular membrane fragments.
Hypophysectomy reduced the inotropic potency of isoprenaline and increased the potency of phenylephrine and methoxamine in left atria. The effect of phenylephrine was inhibited by propranolol less effectively and by phentolamine or phenoxybenzamine more effectively in hypophysectomized than in control rats. The difference in block was smaller at low than at high antagonist concentrations. Similar but smaller changes were observed for chronotropic responses of right atria.
The decreased β‐ and increased α‐receptor response after hypophysectomy was similar to that observed earlier in thyroidectomized rats (Kunos, 1977). These changes developed slowly after hypophysectomy (> 2 weeks), they were both reversed within 2 days of thyroxine treatment (0.2 mg/kg daily), but were not affected by cortisone treatment (50 mg/kg every 12 h for 4 days).
Treatment of hypophysectomized rats for 2 days with thyroxine increased the density of [3H]‐dihydroalprenolol ([3H]‐DHA) binding sites from 27.5 ± 2.7 to 45.5 ± 5.7 fmol/mg protein and decreased the density of [3H]‐WB‐4101 binding sites from 38.7 ± 3.1 to 18.7 ± 2.5 fmol/mg protein. The affinity of either type of binding site for agonists or antagonist was not significantly altered by thyroxine treatment and the sum total of α1‐ and β‐receptors remained the same.
Sympathetic denervation of thyroidectomized rats by 6‐hydroxydopamine increased the inotropic potency of isoprenaline and noradrenaline and the blocking effect of propranolol, and decreased the potency of phenylephrine and the blocking effect of phenoxybenzamine to or beyond values observed in euthyroid controls. The density of [3H]‐DHA binding sites was higher and that of [3H]‐WB‐4101 binding sites was lower in the denervated than in the innervated hypothyroid myocardium. Depletion of endogenous noradrenaline stores by reserpine did not significantly alter the adrenoceptor response pattern of the hypothyroid preparations and did not influence the density or affinity of [3H]‐DHA and [3H]‐WB‐4101 binding sites.
These results indicate that thyrotropin or steroids do not contribute to the reciprocal changes in the sensitivity of cardiac α1‐ and β‐adrenoceptors in altered thyroid states. These thyroid hormone‐dependent changes are probably due to a parallel, reciprocal change in the numbers but not the affinities of α1‐ and β‐adrenoceptors. Reciprocal regulation of cardiac α1‐ and β‐adrenoceptors by thyroid hormones requires intact sympathetic innervation but not the presence of normal stores of the neurotransmitter.
THE INHIBITORY ACTION OF TWO THROMBIN INHIBITORS (TI‐189 AND TI‐233) ON THE CONTRACTILE RESPONSES TO 5‐HYDROXYTRYPTAMINE AND PROSTAGLANDIN ENDOPEROXIDE ANALOGUE (U‐44069) IN ISOLATED VASCULAR STRIPS
Authors: HO WILLIAM K.W. , NAKAO K. , SHIBATA S. 
Published: July 2012

Two arginine derivatives that were developed as thrombin inhibitors (TI‐189 and TI‐233) selectively inhibited the 5‐hydroxytryptamine (5‐HT)‐induced contraction of rabbit aortic strips in a competitive manner. The pA2 values of TI‐189 and TI‐233 were 5.24 ± 0.21 and 6.23 ± 0.32 respectively.
Even at 10−4 m they had no inhibitory effect on the contractile response to noradrenaline (NA), histamine, prostaglandin E2 (PGE2), PGF2α, arachidonic acid or potassium in rabbit aortic strips.
In dog basilar and coronary arterial strips and also in rat fundus, both agents inhibited the 5‐HT response in a non‐competitive manner.
At 10−5 m, TI‐233 but not TI‐189 antagonized effects of NA and KC1 in the dog basilar and coronary arteries.
These arginine derivatives decreased the contractile responses induced by a prostaglandin endoperoxide analogue (U‐44069) in rabbit aorta and in dog basilar and coronary arteries but there was no evidence for competitive antagonism.
These results indicate that the arginine derivatives are competitive antagonists selective for 5‐HT receptors in rabbit aorta.
ERRORS IN THE MEASUREMENT OF AGONIST POTENCY‐RATIOS PRODUCED BY UPTAKE PROCESSES: A GENERAL MODEL APPLIED TO β‐ADRENOCEPTOR AGONISTS
Authors: KENAKIN TERRY P. 
Published: July 2012

The sensitization of guinea‐pig atria and trachea to noradrenaline, isoprenaline, and salbutamol, produced by an inhibitor of neuronal (cocaine) and extraneuronal (metanephrine) uptake, was studied quantitatively. The data were compared to a theoretical model.
Cocaine produced near maximal sensitization to noradrenaline in guinea‐pig atria (5 fold) at concentrations which produced only partial sensitization in guinea‐pig trachea (4.7 fold sensitization of a maximum 11 fold). These results agreed with the model which predicts that there is a direct relationship between the amount of uptake inhibitor required to produce full sensitization and the magnitude of maximal sensitization demonstrable in the tissue. This makes extrapolation of uptake inhibition concentrations from tissue to tissue a potentially erroneous practice.
In normal trachea, salbutamol is 20 times more potent than noradrenaline but this difference is abolished (to 0.9 times) by cocaine (100 μm). This reduction of potency‐ratio is due to the selective cocaine‐induced sensitization of trachea to noradrenaline and raises a serious objection to the classification of salbutamol as a β2 selective agonist.
Metanephrine produced very little sensitization of trachea to isoprenaline. Experiments with salbutamol showed metanephrine to be a simple competitive antagonist of β‐adrenoceptors (pKb = 4.3) and that this receptor antagonism masked sensitization to isoprenaline.
A theoretical model indicates that an inhibitor of agonist uptake requires a remarkable degree of selectivity for the uptake mechanism (i.e. Kb for receptors 104 × K1 for uptake sites) to demonstrate tissue sensitization to the agonist. This analysis and the data with metanephrine indicate that a sinistral shift of the concentration‐response curve is a poor indicator of the importance of uptake mechanisms in an isolated tissue.
An alternate method to determine the importance of agonist‐uptake effects on concentration‐response curves is described which utilizes agonist potency ratios. Agonist potency ratios in guinea‐pig atria and trachea showed that the bronchoselectivity demonstrated by salbutamol (with respect to isoprenaline) is reduced from 54 to 7.8 by metanephrine reflecting the importance of extraneuronal uptake in trachea.
MYOTONIA AS A SIDE EFFECT OF DIURETIC ACTION
Authors: BRETAG A.H. , DAWE S.R. , KERR D.I.B. , MOSKWA A.G. 
Published: July 2012

Commonly used loop diuretics produce side effects in man which are similar to chemically induced myotonia. These diuretics have structural affinity with known myotonic agents.
We have observed EMG myotonia in vivo in leg muscles of rats treated with intravenous frusemide.
In the presence of several different diuretics, rat isolated diaphragm, soleus and extensor digitorum longus muscles as well as frog sartorius muscles produce typically myotonic contractions with relaxation times up to several seconds.
Intracellular recording of action potentials from diuretic‐treated muscles reveals long lasting after‐discharges following a brief electrical stimulus, again typical of chemically induced myotonia.
Having demonstrated a myotonic action of several diuretics we suggest a need for caution in using these drugs in persons with hereditary myotonia and a need to be aware of possible provocation of myotonia in subclinical cases. Myopathies and neuropathies which are known to result from chronic exposure to myotonic agents also need to be considered.
In our study, the diuretic, acetazolamide, unmasked subthreshold myotonia. This seems to be at variance with reports of its usefulness in the treatment of myotonia.
Diuretics should probably not be employed in the treatment of herbicide intoxication where their myotonic activity would be expected to add to the known myotonic activity of the herbicide.
A COMPARISON OF THE ABILITY OF TWO ANGIOTENSIN II RECEPTOR BLOCKING DRUGS, 1‐SAR, 8‐ALA ANGIOTENSIN II AND 1‐SAR, 8‐ILE ANGIOTENSIN II, TO MODIFY THE REGULATION OF GLOMERULAR FILTRATION RATE IN THE CAT
Authors: JOHNS E.J. 
Published: July 2012

Modest stimulation of the renal nerves in the anaesthetized unilaterally nephrectomized cat resulted in a 15% fall in renal blood flow, no change in glomerular filtration rate and significant falls in both the absolute and fractional rates of sodium excretion.
The haemodynamic responses to nerve stimulation were not modified by angiotensin II blockade with 1‐Sar, 8‐Ala angiotensin II although the fall in absolute, but not fractional sodium excretion was significantly larger. In contrast, stimulation of renal nerves following administration of 1‐Sar, 8‐Ile‐angiotensin II caused a significant fall in glomerular filtration rate. The reductions in both absolute and fractional sodium were of the same magnitude as in the absence of drug.
Both renal blood flow and glomerular filtration rate were autoregulated during the reduction of renal perfusion pressure and this was associated with reductions in both absolute and fractional sodium excretions.
In the presence of 1‐Sar, 8‐Ala angiotensin II, the haemodynamic and sodium excretory responses to reductions in renal perfusion pressure were not significantly different from those recorded in the absence of drug. However, following administration of 1‐Sar, 8‐Ile angiotensin II, renal blood flow but not glomerular filtration rate, was autoregulated during reduction in renal perfusion pressure. The falls in absolute and fractional sodium excretions caused by this manoeuvre were of similar magnitude to those obtained in the absence of drug.
The results obtained using the 1‐Sar, 8‐Ile angiotensin II are consistent with angiotensin II having an important intra‐renal site of action to regulate glomerular filtration rate, possibly via an action at the efferent arteriole. Administration of 1‐Sar, 8‐Ala angiotensin II was without effect on the regulation of renal haemodynamics which it is suggested reflects a limitation in the use of this particular compound as an intrarenal angiotensin II antagonist.
EVIDENCE THAT CELL BODIES OF NON‐CHOLINERGIC, EXCITATORY NEURONES WHICH SUPPLY THE SMOOTH MUSCLE OF THE CHICKEN RECTUM ARE LOCATED IN THE GANGLIA OF REMAK'S NERVE
Authors: KANAZAWA T. , OHASHI H. , TAKEWAKI T. 
Published: July 2012

A pharmacological investigation of the distribution of non‐cholinergic excitatory nerve cell bodies was performed on the chicken's isolated perfused rectum with attached Remak's nerve supply.
Electrical stimulation of Remak's nerve trunk produced a contraction and a discharge of action potentials in the nerve branches which supply the smooth muscle of the rectum. Both responses were virtually blocked by hexamethonium when applied via the caudal mesenteric artery.
The contractile effect following stimulation of the nerve trunk was inhibited more effectively by hexamethonium when application was restricted to the trunk rather than to the intestine.
The contractile effect of stimulating the nerve branches was unaffected by hexamethonium.
It is concluded that ganglionic transmission, which is mediated by nicotinic receptors, occurs in the ganglia of Remak's nerve but not in ganglia of the enteric plexuses. Therefore, cell bodies of the postganglionic neurones which are considered to be non‐cholinergic are located in Remak's nerve ganglia.
PRAZOSIN DOES NOT ALTER CANINE RENIN RELEASE IN RESPONSE TO SYSTEMIC HYPOTENSION OR INTRARENAL ISOPRENALINE AND PROSTAGLANDIN I2 INFUSION
Authors: GERBER JOHN G. , NIES ALAN S. , OLSON RICHARD D. 
Published: July 2012

The effect of a hypotensive dose of intravenous prazosin (0.2 mg/kg) on heart rate and plasma renin activity was evaluated in anaesthetized mongrel dogs pretreated with indomethacin.
The effect of prazosin on the renin release elicited by the β‐adrenoceptor agonist isoprenaline and by prostaglandin I2 was also evaluated.
Prazosin administration was associated with a significant increase in heart rate and increase in plasma renin activity.
Prazosin did not interfere with the increase in plasma renin activity in response to either isoprenaline or prostaglandin I2.
We conclude that prazosin is not a unique peripheral vasodilator since hypotensive doses are associated with an increase in heart rate and plasma renin activity. In addition, prazosin does not inhibit the release of renin induced by either isoprenaline or prostaglandin I2.
A STUDY OF γ‐AMINOBUTYRIC ACID UPTAKE IN NORMAL AND DOWN'S SYNDROME PLATELETS
Authors: ENNS LOUISE , McCOY E.E. 
Published: July 2012

Initial uptake rates of γ‐aminobutyric acid (GABA) were compared in Down's syndrome (D.S.) and normal platelets. GABA uptake was decreased in D.S. platelets (1.10 ± 0.10 nmol h−1 10−9) compared to uptake by normal platelets (1.89 ± 0.21 nmol h−1 10−9), P < 0.005.
The effect of varying the Na+ concentration was similar on D.S. and normal platelets. Increasing the media Na+ concentration resulted in increased rates of GABA uptake in both D.S. and normal platelets.
GABA uptake in the presence of 2,4‐dinitrophenol or at 2°C is approximately 56% of the uptake at 37°C for both D.S. and normal platelets.
Extrapolation of a reciprocal plot indicates a two affinity uptake system: a high affinity and a low affinity mechanism.
A significant defect in GABA uptake exists in D.S. platelets.
ACCUMULATION AND OVERFLOW OF 3H FOLLOWING INCUBATION OF THE GUINEA‐PIG GALL BLADDER WITH [3H]‐NORADRENALINE
Authors: DOGGRELL SHEILA A. , VINCENT LYNN 
Published: July 2012

Strips of guinea‐pig gall bladder readily accumulate 3H following incubation in the presence of 5 times 10−8 m (‐)‐[3H]‐noradrenaline. This accumulation was reduced by lowering the incubation temperature (from 37° to 23°C), by cocaine (10−6 m), by nortriptyline (10−8, 10−6 and 10−4 m) and following incubation of the tissues with 6‐hydroxydopamine (10−3 m for 3 h). At 10−6 m, (‐)‐noradrenaline and (‐)‐adrenaline, but not (‐)‐isoprenaline, inhibited the accumulation of 3H.
Following preloading of strips of guinea‐pig gall bladder with 3.6 times 10−7 m (‐)‐[3H]‐noradrenaline for 1 h, the spontaneous overflow of 3H was observed. Cocaine (10−4 m), nortriptyline (10−6 m), (‐)‐isoprenaline (10−5 m), acetylcholine (10−5 m) and adenosine 5′‐triphosphate (ATP, 10−4 m) had no effect on the spontaneous overflow of 3H. KCl (10−1 m), (‐)‐noradrenaline (10−5 m), (‐)‐adrenaline (10−5 m), and tyramine (10−5 m) increased the overflow of 3H. These results illustrate similar characteristics of the guinea‐pig gall bladder to other noradrenergically‐innervated tissues in accumulating and releasing 3H following incubation in the presence of [3H]‐noradrenaline.
Following incubation in the presence of 3.6 times 10−7 m (‐)‐[3H]‐noradrenaline, field stimulation, at 5 Hz, of strips of gall bladder, in the absence or presence of 10−6 m atropine, increased the overflow of 3H and, simultaneously, induced contractions. The contractile responses to 5 Hz were smaller in the presence than in the absence of 10−4 m lignocaine. Lignocaine (10−4 m) reduced the overflow of 3H evoked by field stimulation at 5 Hz. It is suggested that the contractile responses to 5 Hz are due to nerve stimulation and that the increased overflow of 3H is due to the stimulation of noradrenergic nerves.
The overflow of 3H evoked by field stimulation at 5 Hz was unaltered and increased by propranolol (10−6 m) and phentolamine (10−6 m), respectively. Clonidine (5 times 10−5 m) had no effect in the absence but reduced the amount of 3H which overflowed in response to field stimulation at 5 Hz in the presence of 10−6 m atropine. The contractile responses to field stimulation at 5 Hz were reduced by phentolamine (10−6 m) or clonidine (5 times 10−6, 10−5 and 5 times 10−5 m) whether or not atropine (10−6 m) was present. These results illustrate the presence of postsynaptic α‐adrenoceptors and suggest the presence of presynaptic α‐adrenoceptors in the gall bladder of the guinea‐pig.
CHLORPROMAZINE, HALOPERIDOL, METOCLOPRAMIDE AND DOMPERIDONE RELEASE PROLACTIN THROUGH DOPAMINE ANTAGONISM AT LOW CONCENTRATIONS BUT PARADOXICALLY INHIBIT PROLACTIN RELEASE AT HIGH CONCENTRATIONS
Authors: BESSER G.M. , DELITALA G. , GROSSMAN ASHLEY , STUBBS W.A. , YEO T. 
Published: July 2012

The effects of chlorpromazine, haloperidol, metoclopramide and domperidone on the release of prolactin from perfused columns of dispersed rat anterior pituitary cells were studied.
Chlorpromazine, haloperidol, metoclopramide and domperidone antagonized the dopamine‐mediated inhibition of prolactin release at low concentrations.
Each dopamine antagonist displaced the dose‐response curve for dopamine‐induced suppression of prolactin release to the right in a parallel manner.
At higher concentrations, the four drugs became less effective as dopamine antagonists.
At high concentrations in the absence of dopamine, chlorpromazine, haloperidol, metoclopramide and domperidone paradoxically suppressed prolactin secretion by an unknown mechanism.
CHARACTERISTIC CONTRACTILE RESPONSE TO THE CALCIUM IONOPHORE, A23187, IN GUINEA‐PIG VAS DEFERENS
Authors: ISHIDA YUKISATO , SHIBATA SHOJI 
Published: July 2012

In the guinea‐pig isolated vas deferens, the calcium ionophore, A23187, initially caused a phasic contraction followed by rhythmic activity.
Treatment with atropine, phentolamine, tetrodotoxin and reserpine modified neither of the components of the contraction induced by the ionophore. Verapamil and nifedipine abolished the rhythmic activity but had no effect on the phasic contraction.
In a calcium‐free solution, both components of the contraction were abolished.
It is suggested that A23187 is able to cause contraction by a direct action on the smooth muscle of guinea‐pig vas deferens.
PROPHYLACTIC LIGNOCAINE AND EARLY POST‐CORONARY ARTERY OCCLUSION DYSRHYTHMIAS IN ANAESTHETIZED GREYHOUNDS
Authors: MARSHALL R.J. , PARRATT J.R. 
Published: July 2012

Lignocaine (1 mg kg−1 min−1 infused intravenously for 30 min) greatly reduced the incidence of ventricular ectopic beats that resulted from acute coronary artery ligation in anaesthetized greyhound dogs. However, the incidence of ventricular fibrillation was only slightly reduced by this treatment which caused significant myocardial depression.
There is no good evidence from this study that lignocaine is a particularly effective prophylactic in acute myocardial infarction.
SUBSTANCE P INCREASES HYPOTHALAMIC BLOOD FLOW VIA AN INDIRECT ADRENERGIC‐CHOLINERGIC INTERACTION
Authors: KLUGMAN K.P. , LEMBECK F. , MARKOWITZ S. , MITCHELL G. , ROSENDORFF C. 
Published: July 2012

Hypothalamic blood flow (HBF) was measured in conscious rabbits by the 133xenon washout technique.
Substance P in a dose of 50 or 500 ng increases HBF while 5 ng is without effect.
Cholinoceptor blockade, with either atropine or mecamylamine abolishes the vasodilator effect of substance P.
Chemical sympathectomy of the hypothalamus with 6‐hydroxydopamine, or adrenoceptor blockade with either propranolol or phenoxybenzamine abolishes the effect of substance P on HBF.
Destruction of the intracerebral noradrenergic pathway (INP), or blockade of its vasodilator action, with barbiturate or bicarbonate, likewise prevent the vasodilator action of substance P.
These results suggest that substance P may cause an increase in HBF via the release of endogenous acetylcholine, which in turn stimulates the INP.
INVESTIGATION OF THE ANTIFIBRILLATORY ACTIVITY OF SOME ANTICONVULSANT γ‐AMINOBUTYRIC ACID‐TRANSAMINASE INHIBITORS IN THE RABBIT ISOLATED HEART: COMPARISON WITH PHENYTOIN AND MEXILETINE
Authors: ALMOTREFI A.A. , BAKER J.B.E. 
Published: July 2012

The electrical stimulation and ventricular fibrillation thresholds were measured in the Langendorff‐perfused rabbit heart by application of rectangular impulses of 3 ms duration and increasing current at frequencies of 4 and 20 Hz respectively.
Perfusion with either phenytoin or mexiletine produced significant dose‐dependent increases in both thresholds.
Perfusion with four anticonvulsant inhibitors of γ‐aminobutyric acid (GABA)‐transaminase, amino‐oxyacetic acid, γ‐acetylenic GABA, γ‐vinyl GABA and sodium valproate, up to a concentration of 20 μg/ml, had no significant effect on either threshold.
The results suggest that these compounds, unlike phenytoin and mexiletine, are devoid of antifibrillatory activity.
THE EFFECT OF CHRONIC MORPHINE TREATMENT ON EXCITATORY JUNCTION POTENTIALS IN THE MOUSE VAS DEFERENS
Authors: NORTH R.A. , VITEK L.V. 
Published: July 2012

Intracellular recordings were made from smooth muscle cells of vasa deferentia in vitro. Vasa from two groups of mice were studied; the first were naive and the second had been chronically pretreated with morphine for 3 days. The vasa from morphine‐pretreated mice were maintained in Krebs solution containing normorphine (300 nm).
The resting membrane potentials of the smooth muscle cells were the same in both groups of mice.
The excitatory junction potentials (e.j.ps) evoked by stimulation of the intramural nerves were depressed by normorphine in both groups of mice. The EC50 for this action of normorphine was 560 nm for the naive group and 6.6 μm for the morphine‐pretreated group.
The EC50 for adenosine in depressing e.j.p. amplitude was the same in the two groups.
Naloxone did not change the resting membrane potential in cells from either group of mice. In morphine‐pretreated mice, naloxone caused a marked increase in the amplitude of the evoked e.j.p.
The EC50 for noradrenaline in causing a contractile response of the isolated vas deferens was the same in both groups of mice.
The results indicate that changes in postsynaptic sensitivity to transmitter do not occur following morphine pretreatment.