bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of thyroid status on responses of rat isolated pulmonary artery, vas deferens and trachea to smooth muscle relaxant drugs
Authors: O'Donnell Stella R. , Wanstall Janet C. , Mustafa Mariana B.H. 
Published: July 2012

Responses to relaxant drugs have been examined on isolated KCl‐contracted smooth muscle preparations from rats in which thyroid status was changed by prior treatment with either thyroxine (T4) for 1 week (preparations of pulmonary artery, trachea and vas deferens) or methimazole for 10–12 weeks (pulmonary artery preparations).
On pulmonary artery preparations, T4 treatment caused a significant increase in the magnitude of the relaxant responses to noradrenaline and isoprenaline but not those to adrenaline. The potency of noradrenaline was increased 5.6 fold but that of isoprenaline and adrenaline was unchanged. This resulted in a change in the relative potencies from adrenaline > noradrenaline (controls) to noradrenaline = adrenaline (T4‐treated). Methimazole treatment caused a significant reduction in the magnitude of the responses to noradrenaline and in its potency (2.8 fold). Isoprenaline and procaterol were unaffected.
On pulmonary artery preparations, T4 treatment did not affect the magnitude of the responses to forskolin, sodium nitrite or isobutylmethylxanthine (IBMX) or their potency. In vitro treatment with the monoamine oxidase (MAO) inhibitors, iproniazid or pargyline, did not potentiate responses to either noradrenaline or isoprenaline. Therefore, it was concluded that the T4‐induced changes in the magnitude of the responses to noradrenaline and isoprenaline and in the potency of noradrenaline were unlikely to be due to reduced activity of cyclic nucleotide phosphodiesterase(s) or MAO.
On preparations of vas deferens and trachea, T4 treatment had no effect on the magnitude of the responses to noradrenaline, isoprenaline, adrenaline or procaterol. On preparations of trachea, but not vas deferens, T4 treatment significantly increased the potency of noradrenaline (2.9 fold) but not that of isoprenaline, adrenaline or procaterol.
We concluded that, on pulmonary artery T4 treatment of rats increased, while methimazole treatment reduced, the magnitude of the responses to, and/or the potency of, the β‐adrenoceptor agonists, noradrenaline and isoprenaline, by a mechanism which is specifically associated with the β‐adrenoceptors, and which is probably selective for the β1‐subtype. T4 treatment caused no change in responses of vas deferens to β‐adrenoceptor agonists. On trachea the only change was a small increase in the potency of noradrenaline. The differences in the effects of T4 treatment on β‐adrenoceptor‐mediated responses of rat pulmonary artery, vas deferens and trachea may be due to the differences in the β‐adrenoceptor populations of these three tissue types and/or differences in the effects of thyroid hormones on vascular compared with non‐vascular smooth muscle.
Characterization and autoradiographic localization of β‐adrenoceptor subtypes in human cardiac tissues
Authors: Buxton B.F. , Jones C.R. , Molenaar P. , Summers R.J. 
Published: July 2012

Receptor autoradiography using (—)‐[125I]‐cyanopindolol (CYP) was used to study the distribution of β‐adrenoceptor subtypes in human right atrial appendage, left atrial free wall, left ventricular papillary muscle and pericardium.
The binding of (—)‐[125I]‐CYP to slide‐mounted tissue sections of human right atrial appendage was time‐dependent (K1 = 4.11 ± 1.01 × 108 m−1 min−1, K−1 = 1.47 ± 0.25 × 10−3 min−1, n = 3), saturable (42.02 ± 2.96 pM, n = 4) and stereoselective with respect to the optical isomers of propranolol (pKD (—):8.97 ± 0.02, (+):6.88 ± 0.06, n = 3).
The proportions of β‐adrenoceptor subtypes were determined in slide‐mounted tissue sections using the antagonists CGP 20712A (β1‐selective) and ICI 118,551 (β2‐selective). In right atrial appendage and left ventricular papillary muscle 40% (34–45%) of the β‐adrenoceptors were of the β2‐subtype.
Images from X‐ray film and nuclear emulsion coated coverslips exposed to (—)‐[125I]‐CYP‐labelled sections showed an even distribution of β‐adrenoceptor subtypes over the myocardium of the right atrial appendage, left ventricular papillary muscle and left atrial free wall. Sections of pericardium exhibited predominantly β2‐adrenoceptors. β2‐Adrenoceptors were localized to the intimal surface of coronary arteries.
The selective β1‐adrenoceptor agonist R0363 and β2‐selective agonist procaterol produced concentration‐dependent inotropic responses in right atrial appendage strips. Responses to R0363 were antagonized by CGP 20712A (pKB = 9.29) suggesting an interaction with β,‐adrenoceptors. Responses to procaterol were antagonized by ICI 118,551 (pKB = 9.06) suggesting an interaction at β2‐adrenoceptors.
The finding that a significant proportion of human myocardial adrenoceptors are of the β2‐subtype has important clinical implications for the involvement of these receptors in the control of heart rate and force, and the autoradiographic evidence suggests other roles in the coronary vasculature and pericardium.
l‐Proline depolarizes rat spinal motoneurones by an excitatory amino acid antagonist‐sensitive mechanism
Authors: Ault Brian , Wang Ching M. , Yawn Beverly C. 
Published: July 2012

Isolated spinal cords prepared from neonatal rats were used to examine the effects of l‐proline (l‐Pro).
l‐Pro (1–8 mm) depolarized ventral and dorsal roots in a dose‐dependent manner with one sixth of the potency of l‐glutamate (l‐Glu). l‐Pro was four times more potent than d‐Pro. Prolonged application of l‐Pro produced a plateau depolarization of motoneurones with no apparent fade.
Omission of calcium ions from the medium potentiated the depolarizing actions of l‐Pro, l‐Glu and quisqualate.
L‐Pro was antagonized by concentrations of 2‐amino‐5‐phosphonovalerate (25 μm), γ‐d‐glutamylglycine (100 μm) and Mg2+ ions (1 mm) that depressed responses to N‐methyl‐d‐aspartate (NMDA). The NMDA receptor‐mediated component of the response to l‐Pro was estimated to be 60–70%.
These data suggest that l‐Pro should be considered as a possible excitatory neurotransmitter and that, because l‐Pro is a neutral compound, excitatory amino acid receptors may not require an agonist to possess two anionic groups and one cationic group.
The effects of agonists on the components of the cardiac muscarinic receptor
Authors: Burgen A.S.V. 
Published: July 2012

The binding of eleven agonists to muscarinic receptors in the rat heart has been measured in competition with [3H]‐N‐methylscopolamine.
Full analysis of binding required the resolution of three components (SH, H and L).
The proportion of the H component was independent of agonist structure. The proportion of the SH component ranged from 2–36% of the total and was dependent on the agonist. The proportion of the L component varied in a complementary way from 59‐22% of the total.
The ratios of the affinities of ten of the agonists to the three components of the receptors were constant; the weakest binding agonist, choline, had lower ratios of affinity.
When saturated with guanylylimidodiphosphate (GppNHp) the SH receptor population was no longer detectable and the H receptor population was reduced by 63%: about 85% of the receptors was in the L population.
The affinity constants of agonists for the H and L forms of the receptors were not changed by GppNHp.
The results are interpreted in terms of the effects of accessory proteins on the proportions of binding and non‐binding conformations of the receptor.
Effects of amiodarone and thyroid dysfunction on myocardial calcium, serum calcium and thyroid hormones in the rat
Authors: Gammage M.D. , Franklyn J.A. , Logan S.D. 
Published: July 2012

Myocardial calcium content was found to be elevated and serum calcium reduced in hypothyroid rats.
Treatment of rats with amiodarone at either 30 mg kg−1 or 150 mg kg−1 daily did not result in any significant changes in myocardial or serum calcium.
The administration of amiodarone to hypothyroid rats attenuated the changes in serum but not myocardial calcium, suggesting that amiodarone may exert a thyroid hormone‐like effect in the hypothyroid state.
The administration of amiodarone to thyroid hormone‐treated rats resulted in attenuation of the effects on serum calcium and calculated intracellular calcium; this was consistent with an antagonistic interaction between amiodarone and thyroid hormones.
Administration of amiodarone resulted in significant changes in circulating thyroid hormone levels in the rat; triiodothyronine was reduced and basal thyrotrophin elevated compared to euthyroid controls. Serum thyroxine was not changed; this is in contrast to the effects in man.
Amiodarone does not exert its anti‐arrhythmic action via changes in total myocardial calcium content in the euthyroid rat; nonetheless the described interactions between the drug and thyroid hormones may be involved in its mechanism of action.
A study on the effect of a single dose of tamoxifen on uterine hyperaemia and growth in the rat
Authors: Marshall K. , Senior J. 
Published: July 2012

The effect of a single subcutaneous dose of tamoxifen on the rat uterotrophic response was investigated.
The parameters examined were uterine blood flow (measured by the microsphere technique), uterine wet and dry weights and the concentrations of cytosolic and nuclear oestrogen receptors.
Tamoxifen or its metabolites proved to be capable of eliciting a uterotrophic response of 35–42 days duration. The changes seen in uterine blood flow and weight are discussed in relation to oestrogen receptor distribution.
Effect of chlorpromazine on sympathetic neuroeffector transmission in the rabbit isolated pulmonary artery and aorta
Authors: Nedergaard O.A. , Abrahamsen J. 
Published: July 2012

The effects of chlorpromazine on sympathetic neuroeffector transmission have been studied in the rabbit isolated pulmonary artery and aorta.
Chlorpromazine (10−8‐10−5 m), prazosin (10−9‐10−7 m) and phentolamine (3 × 10−8‐3 × 10−5 m) decreased the contractions of pulmonary artery evoked by electrical field stimulation (150 pulses; 3 Hz). The rank order of inhibitory potency (ID50) was prazosin > chlorpromazine > phentolamine.
Rauwolscine (3 × 10−9 m‐4 × 10−6 m) enhanced the neurogenic response by up to 201%. However, higher concentrations (6 × 10−6‐3 × 10−5 m) reduced the contractions evoked by transmural stimulation.
The inhibitory effect of prazosin (10−6 m) was reversible, while that of chlorpromazine (10−8 m) was not.
Chlorpromazine (10−8‐10−4 m), desmethylimipramine (3 × 10−9‐10−5 m), cocaine (10−7‐3 × 10−4 m) and phentolamine (10−5‐3 × 10−4 m) reduced the accumulation of [3H]‐noradrenaline ([3H]‐NA, 10−8 m) by aorta. The rank order of inhibitory potency (ID50) was: desmethylimipramine > chlorpromazine > cocaine > phentolamine. Prazosin (10−7‐10−5 m) and rauwolscine (10−8‐10−4 m) did not reduce [3H]‐NA accumulation.
Chlorpromazine (10−8‐10−6 m) and prazosin (3 × 10−9‐10−7 m) antagonized the contractions of aorta evoked by exogenous noradrenaline (10−9‐3 × 10−4 m) and phenylephrine (10−9‐3 × 10−3 m). The pA2 values for chlorpromazine on the α1‐adrenoceptors were 8.24 (noradrenaline) and 8.27 (phenylephrine). The corresponding values for prazosin were 8.64 and 8.57, respectively.
It is concluded that chlorpromazine and prazosin are potent inhibitors of postsynaptic α1‐ adrenoceptors. Chlorpromazine and phentolamine, unlike prazosin and rauwolscine, are also inhibitors of Uptake.
The cholecystokinin receptor antagonist L364,718 increases food intake in the rat by attenuation of the action of endogenous cholecystokinin
Authors: Hewson G. , Leighton G.E. , Hill R.G. , Hughes J. 
Published: July 2012

To determine the role of endogenous cholecystokinin (CCK) in the regulation of food intake, the effects of the potent CCK receptor antagonist L364,718 were investigated on the intake of a palatable diet in non‐deprived rats. The effect of a single dose of proglumide was also investigated for comparative purposes. In addition, the ability of L364,718 to antagonize the reduction in food intake produced by exogenous cholecystokinin‐octapeptide (CCK8) or bombesin in food‐deprived rats was determined.
L364,718 (10–100 μg kg−1, i.p.) increased the intake of palatable diet during the 30 min test period. Proglumide (300 mg kg−1, i.p.) also increased the intake of palatable diet. Conversely, CCK8 (0.5–5 μg kg−1, i.p.) produced a reduction in the intake of the diet.
In fasted rats, L364,718 (100 μg kg−1, i.p.) antagonized the reduction in food intake produced by CCK8 (10 μg kg−1, i.p.) but not that produced by bombesin (50 μg kg−1, i.p.). L364,718 did not increase food intake in these animals when measured over a 6 h period.
It is concluded that L364,718 is a potent, selective antagonist of the effects of CCK8 on food intake. The observation that L364,718 and proglumide increase the intake of a palatable diet provides some evidence that endogenous CCK is involved in the control of food intake in this model.
Antinociceptive effects of the novel opioid peptide BW443C compared with classical opiates; peripheral versus central actions
Authors: Follenfant R.L. , Hardy G.W. , Lowe L.A. , Schneider C. , Smith T.W. 
Published: July 2012

To investigate peripherally mediated antinociceptive effects of opioids, the activity of a novel polar enkephalin analogue H‐Tyr‐d‐Arg‐Gly‐Phe (4‐NO2)‐Pro‐NH2 (BW443C) has been compared with those of classical tertiary opiates against different nociceptive stimuli in the mouse.
In chemically‐induced writhing models BW443C, administered subcutaneously, demonstrated dose‐related antinociceptive effects less potent than morphine and of a similar order to pethidine and d‐propoxyphene. In assays using heat as the noxious stimulus BW443C was markedly less potent than any of the opiates tested.
In heat‐induced assays, but not in chemically‐induced writhing assays, BW443C demonstrated a ‘U’‐shaped dose‐time response relationship. Morphine, pethidine and d‐propoxyphene showed simple, approximately linear, dose‐time effects in all assays.
When given subcutaneously, the inhibitory effects of BW443C and morphine in chemically‐induced writhing were antagonized by naloxone given intraperitoneally. The inhibitory effects on writhing of BW443C, but not those of morphine, were also antagonized by prior intraperitoneal administration of the quaternary opioid antagonist N‐methyl nalorphine. When this antagonist was administered intracerebroventricularly, the antinociceptive effects in writhing of both BW443C and morphine were antagonized.
It is concluded that BW443C, being only poorly able to cross the blood brain barrier, demonstrates peripherally mediated opioid antinociceptive effects in chemically‐induced writhing models. In heat‐induced models, that detect centrally acting opioids, BW443C is effective only at high doses and at time intervals after dosing sufficient to allow slow penetration of drug into the CNS. It is suggested that the peripheral antinociceptive actions of BW443C are mediated by inhibition of sensory neurones.
Differential antagonism by Bay K 8644 of vasodilator effects of nifedipine, diltiazem, nicorandil and nitroglycerin in dog femoral circulation
Authors: Sato Yoshinori , Ishii Kuniaki , Taira Norio 
Published: July 2012

The modification by Bay K 8644 of the vasodilator effects of nifedipine, diltiazem, nicorandil and nitroglycerin was investigated in the femoral arterial bed of anaesthetized dogs.
The right femoral artery was cannulated and its arterial bed was perfused with autologous blood at a constant pressure slightly higher than the mean systemic arterial blood pressure. Bay K 8644 was infused intra‐arterially (i.a.) and the 4 vasodilators were injected i.a. as bolus doses.
The vasodilator effects of nifedipine (0.3–10 nmol), diltiazem (0.01–1 μmol), nicorandil (0.1–10 μmol) and nitroglycerin (0.3–100 nmol) were all suppressed by infusions of Bay K 8644 (3–100 nmol min−1).
The dose‐response curve of nifedipine was shifted parallel to the right by the infusion of Bay K 8644 and the dose‐ratio was the greatest of the 4 drugs.
The dose‐response curve of diltiazem was also shifted to the right by Bay K 8644. However, the dose‐ratio was far smaller than that of nifedipine.
The vasodilator effect of nicorandil was not antagonized as much by Bay K 8644 as that of nitroglycerin. This less effective antagonism of nicorandil by Bay K 8644 can be explained if nicorandil, which although structurally a nitrate, can in addition cause relaxation of vascular smooth muscle by hyperpolarizing the membrane which would result in Bay K 8644 being less effective.
Effect of dopamine antagonists on the urine flow of rats infused with hypotonic saline
Authors: Angchanpen Pichian , Marin‐Grez Marcos , Schnermann Jürgen 
Published: July 2012

The probable involvement of dopamine in the regulation of water excretion was investigated by administering dopamine antagonists intravenously to barbiturate ‐ anaesthetized rats undergoing a water diuresis induced by the infusion of 0.83% glucose with 0.3% NaCl at the rate of 9 ml h−1.
Administration of 100 μg of the D1‐/D2‐dopamine antagonist, haloperidol, reduced the enhanced urine flow of rats infused with the hypotonic solution by 69% (from 75.4 ± 13.0 to 23.6 ± 6.0 μl min−1, P < 0.01). Similarly, the D1‐receptor antagonist, SCH 23390, reduced urine flow by 58% (from 77.5 ± 9.2 to 32.7 ± 7.2 μl min−1, P < 0.01) and the D2‐receptor antagonist, sulpiride, by 47% (from 66.2 ± 8.6 to 35.1 ± 6.8 μl min−1, P < 0.05).
The injection of SCH 23390 increased the urine osmolality from 189.6 ± 27.5 to 479.8 ± 45.8 mosm kg−1 (P < 0.05). There was no significant change in sodium and potassium excretion in any of the experiments. Blood pressure (BP) decreased after haloperidol and SCH 23390 injection from control values of 121.7 ±1.7 and 116.5 ±7.4 to 113.3 ±3.3 and 106.0 ± 8.8 mmHg respectively (P < 0.05).
To study whether the influence of dopamine antagonists on urine flow during water diuresis depends on antidiuretic hormone (ADH), we administered 0.6 μg d(CH2)5‐D‐Phe‐Ile‐AVP (an ADH antagonist) shortly after the injection of 100 μg SCH 23390. The preferential V2 ADH‐antagonist abolished the antidiuretic effect of SCH 23390 but did not affect its blood pressure reducing effect (from 118.6 ± 5.6 to 103.2 ± 4.6 mmHg, P < 0.01).
These results suggest that dopamine antagonists blunted the hypotonic saline‐induced diuresis by favouring ADH release through an interference with an inhibitory dopaminergic pathway.
Cardiac and renovascular effects in the anaesthetized dog of BW A575C: a novel angiotensin converting enzyme inhibitor with β‐adrenoceptor blocking properties
Authors: Cambridge D. , Whiting M.V. , Allan G. 
Published: July 2012

In the anaesthetized open‐chest dog, BW A575C (N‐(1‐(S)‐carboxy‐5‐[4(3‐isopropylamino‐2‐(R,S)‐hydroxypropoxy)indole‐2‐carboxamido]pentyl)‐(R,S)‐alanyl‐(S)‐proline) causes a dose‐dependent inhibition of the isoprenaline response (increased cardiac rate). In this preparation BW A575C is approximately 50 times less active than propranolol, and 500 times less active than pindolol at the cardiac β1‐adrenoceptor.
At equieffective cardiac β1‐adrenoceptor blocking doses in the anaesthetized, open‐chest dog, BW A575C (5.0 mg kg−1, i.v.) significantly reduces diastolic blood pressure and reduces cardiac contractility and rate. By contrast, propranolol (0.1 mg kg−1, i.v.) and pindolol (0.01 mg kg−1, i.v.) have little effect on diastolic blood pressure, but significantly reduce cardiac contractility and rate. The effects of BW A575C on cardiac rate are not significantly different from those of propranolol and pindolol, but its effects on cardiac contractility are significantly less than those of propranolol. BW A575C also produces some increase in left ventricular internal dimensions at end‐diastole. This small cardiac dilatation is not significantly different from that observed with pindolol but is significantly less than that of propranolol.
In the anaesthetized closed‐chest dog, BW A575C causes a dose‐dependent inhibition of the angiotensin I pressor response. In this preparation BW A575C is approximately equiactive with enalapril at preventing the pressor response due to conversion of exogenous angiotensin I to angiotensin II (inhibition of angiotensin converting enzyme (ACE)).
At equieffective ACE‐inhibition doses in the anaesthetized, closed‐chest dog, BW A575C (1.0 mg kg−1 by i.v. infusion) significantly reduces diastolic blood pressure, cardiac contractility and rate, whereas enalapril (1.0 mg kg−1 by i.v. infusion) only significantly reduces diastolic blood pressure. This blood pressure lowering effect of enalapril is not significantly different from that of BW A575C. In this preparation BW A575C and enalapril also significantly increase renal blood flow, and renal excretion of urine and Na+. There is however no significant difference between their renovascular effects.
These studies demonstrate that BW A575C produces changes in cardiac and renovascular function which can be ascribed to its being an ACE‐inhibitor and a β‐adrenceptor blocking agent. The combination of these pharmacological properties results in a fall in blood pressure without compromising either cardiac performance or renal function.
Involvement of α‐adrenoceptors in myometrial responses in the pro‐oestral rat
Authors: Acritopoulou‐Fourcroy Stella , Marçais‐Collado Hélène 
Published: July 2012

Myometrial responses to different agents acting on adrenoceptors were examined in vivo in the pro‐oestrous rat. Changes in spontaneous uterine mechanical activity were recorded isometrically and evaluated in terms of amplitude and duration of uterine contractions.
Phenylephrine (10 μg kg−1) markedly increased the amplitude and duration of contractions and 40 μg kg−1 gave rise to tetanic contractions.
Administration of either nicergoline (400 μg kg−1) or phentolamine (1000 μg kg−1) to phenylephrine‐primed rat uterus reduced the strength of contractions and phentolamine abolished the phenylephrine‐induced uterine contracture.
Following blockade of α2‐adrenoceptors by yohimbine (1000 μg kg−1) and β‐adrenoceptors by propranolol (2400 μg kg−1), a single injection of phenylephrine (100 μg kg−1) increased the amplitude of uterine contractions by 30%.
Noradrenaline reduced the amplitude of contractions and caused elevation of the baseline level. The response of myometrium to the combination of both propranolol and noradrenaline was the establishment of uterine contracture with subsequent increase of the duration of contractions.
These results clearly demonstrate the involvement of α‐adrenoceptors in the myometrial activity of the rat in vivo during pro‐oestrus.
Suppressive effects of somatostatin in dog Purkinje fibres
Authors: Lin Cheng‐I , Su Mei‐Tsu , Luk Hsiang‐Ning , Wu Hsueh‐Ling 
Published: July 2012

The effects of somatostatin (SS, 1 nm‐3 μm) on the electrical and mechanical activities of isolated Purkinje fibres of the dog were studied.
In most Purkinje fibres driven electrically in normal [K]o Tyrode solution, SS decreased the force of contraction slightly and had very little effect on the fast response action potential. However, in sensitive fibres SS induced a moderate reduction of action potential duration and contractile force in normal [K]o and depressed the slow response action potentials in high [K]o.
In spontaneously beating Purkinje fibres, SS decreased the regular rhythms slightly but abolished bursts of fast rhythms at a concentration as low as 1 nm.
When the fibres were depolarized in the presence of 0.2 mm barium or in Na‐free solution, SS suppressed the Ca‐dependent slow response action potentials.
These findings suggest that SS may suppress abnormal automatic activity of dog Purkinje fibres through a reduction of transmembrane Ca influx or a modulation of intracellular calcium.