bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE RELEASE OF ENDOGENOUS CATECHOLAMINES IN THE CAT HYPOTHALAMUS IS AFFECTED BY SPINAL TRANSECTION AND DRUGS WHICH CHANGE THE ARTERIAL BLOOD PRESSURE*
Authors: DIETL H. , EISERT A. , KRAUS A. , PHILIPPU A. 
Published: January 2008

In anaesthetized cats, posterior and anterior hypothalamic areas were superfused with CSF through double‐walled cannulae. The release of endogenous catecholamines (dopamine, noradrenaline and adrenaline) was determined in the superfusate by a radioenzymatic assay.
Transection of the brain caudal to the hypothalamus almost abolished the release of catecholamines in the posterior hypothalamic area, while that in the anterior hypothalamic area was moderately decreased. A circular transection around the hypothalamus greatly reduced the release of catecholamines in the anterior hypothalamic area. It is concluded that the catecholaminergic nerve endings of the anterior hypothalamic area do not originate entirely from cell bodies located in the brain stem.
Spinal transection elicited a pressor response which was followed by a fall of the arterial blood pressure. The pressor response was associated with increased rates of release of the catecholamines in the anterior hypothalamic area, while the release of catecholamines in the posterior hypothalamic area was reduced. The fall of blood pressure enhanced the rates of release of the catecholamines in the posterior hypothalamic area and reduced their release in the anterior hypothalamic area.
Chlorisondamine i.v. caused a fall of blood pressure which was associated with an increased release of catecholamines in the posterior hypothalamic area and a decrease in the rates of release in the anterior hypothalamic area whilst i.v. tramazoline elicited a pressor response and enhanced the rates of release of the catecholamines in the anterior hypothalamic area.
It is concluded that pronounced changes in the arterial blood pressure affect the release of catecholamines in opposite direction in the two hypothalamic areas to counteract the blood pressure change.
BETA‐ADRENORECEPTORS OF THE CAT NICTITATING MEMBRANE
Authors: VARMA D. R. , NICKERSON M. 
Published: January 2008

The relaxant effects of isoprenaline, salbutamol, adrenaline and noradrenaline on the partially contracted isolated nictitating membrane of the cat were determined in the absence and the presence of α‐adrenoreceptor blockade.
It was possible to demonstrate significant relaxant effects of isoprenaline and salbutamol in the absence as well as in the presence of α‐adrenoreceptor blockade. However, the relaxant effects of adrenaline and noradrenaline could not be demonstrated in the absence of α‐adrenoreceptor blockade.
Molar concentrations (EC30) of isoprenaline, salbutamol and adrenaline causing 30% relaxation of the tone did not significantly differ from each other; EC30 of each of these agents was significantly less than that of noradrenaline.
β1‐Adrenoreceptor antagonist metoprolol was less potent than β2‐antagonist H 35/25 in antagonizing the effect of salbutamol; metoprolol was more potent than H 35/25 in antagonizing noradrenaline. Both these agents were effective antagonists of isoprenaline; however, metoprolol and H 35/25 in combination produced greater antagonism of isoprenaline than did each antagonist separately.
It is concluded that the cat nictitating membrane possesses both β1‐ and β2‐adrenoreceptors which are responsible for the relaxant effects of sympathomimetic agents. A study of these receptors is, however, complicated by concomitant stimulation of α‐adrenoreceptors.
PHARMACOLOGICAL INVESTIGATION OF α‐ADRENORECEPTORS IN GUINEA‐PIG SPLENIC CAPSULE
Authors: DIGGES K. G. , McPHERSON G. A. , SUMMERS R. J. 
Published: January 2008

A study has been made of α‐adrenoreceptors in the smooth muscle of the guinea‐pig splenic capsule.
In this preparation, noradrenaline (NA), adrenaline (Adr) and α‐methyl‐NA were full agonists, while phenylephrine, dopamine and the catechol‐imidazolidine (3,4‐dihydroxyphenylamino)‐2‐imidazolidine, (DPI) were partial agonists.
The imidazolidines clonidine and oxymetazoline showed no agonist activity, but both inhibited the agonist activity of NA. pA2 values calculated from Arunlakshana and Schild plots were 6.88 and 6.95 for clonidine and oxymetazoline respectively. Slopes of the Schild plots were close to unity, indicating competitive antagonism.
The α‐adrenoreceptor antagonists phentolamine, prazosin and yohimbine also inhibited the agonist activity of NA with mean pA2 values of 8.32, 9.22 and 6.90 respectively. Slopes of Schild plots were significantly less than 1, suggesting that the inhibition was not truly competitive in nature.
The irreversible α‐adrenoreceptor antagonist phenoxybenzamine at low concentrations (10–9M) shifted the log concentration‐response curve to NA to the right and greatly reduced the maximum response.
It is suggested that the adrenoreceptors in the guinea‐pig splenic capsule are probably of the α1‐type, and that this tissue possesses relatively few spare receptors.
HYPOTHALAMIC SUPERFUSION WITH HISTAMINE AGONISTS AND ANTAGONISTS MODIFIES THE PRESSOR RESPONSE TO HYPOTHALAMIC STIMULATION*
Authors: PHILIPPU A. , WIEDEMANN K. 
Published: January 2008

To investigate the effect of hypothalamic application of histamine agonists and antagonists on the pressor response to hypothalamic stimulation, the posterior hypothalamus of anaesthetized cats was superfused with drugs through a push‐pull cannula and electrically stimulated with the non‐insulated tip of the cannula.
Superfusion of the posterior hypothalamic area with histamine enhanced the pressor response to hypothalamic stimulation. The most pronounced effect of histamine was found, when the caudal region of the posterior hypothalamic area was superfused. The enhancing effect of histamine was abolished when the hypothalamus was pre‐superfused with metiamide; it was slightly inhibited by pre‐superfusion with mepyramine.
Dimaprit also enhanced the pressor response to hypothalamic stimulation; the effect of this drug was abolished by metiamide, whilst hypothalamic pre‐superfusion with mepyramine was ineffective.
Superfusion of the hypothalamus with 2‐methylhistamine did not change the pressor response to hypothalamic stimulation.
The enhancing effect of histamine was abolished by hypothalamic pre‐superfusion with phentolamine, phenoxybenzamine or propranolol.
It is concluded that histamine enhances the pressor response to hypothalamic stimulation mainly by acting on H2‐receptors of the posterior hypothalamus. The inhibition of the effect of histamine by α‐and β‐adrenoreceptor blocking agents indicates the involvement of catecholaminergic systems of the hypothalamus.
PHARMACOLOGICAL CHARACTERISTICS OF SPINAL α‐ADRENORECEPTORS IN RATS
Authors: CONNOR HELEN E. , DREW G. M. , FINCH L. , HICKS P. E. 
Published: January 2008

Spinal α‐adrenoreceptors involved in cardiovascular control have been investigated using selective α‐adrenoreceptor agonists and antagonists in urethane‐anaesthetized rats.
Intrathecal injections of clonidine, α‐methylnoradrenaline, guanfacine and M7 at the C7‐T1 level reduced blood pressure and heart rate. In contrast, phenylephrine, 5‐hydroxytryptamine and procaine had little or no effect. These results suggest the involvement of spinal α2‐adrenoreceptors.
The fall in blood pressure produced by clonidine appeared to be attributable to a reduction in heart rate and stroke volume. Lower body vascular resistance was unchanged.
The clonidine‐induced bradycardia was antagonised by prazosin, WB4101, piperoxan or yohimbine. Their relative potencies suggest that α1‐ rather then α2‐adrenoreceptors mediate this response.
Piperoxan and yohimbine clearly prevented the clonidine‐induced fall in blood pressure; prazosin and WB4101 also appeared to antagonise clonidine but these results were complicated by the fact that these antagonists themselves reduced blood pressure.
It was difficult to interpret these results simply in terms of α1‐ or α2‐adrenoreceptors. Thus spinal α‐adrenoreceptors may be different from peripheral α1‐ or α2‐adrenoreceptors.
STUDIES ON THE PRE‐ AND POSTJUNCTIONAL ACTIVITIES OF α‐ADRENORECEPTOR AGONISTS AND THEIR CARDIOVASCULAR EFFECTS IN THE ANAESTHETIZED RAT
Authors: DOXEY J. C. , FRANK LEONIE W. , HERSOM A. S. 
Published: January 2008

The selectivity of a number of agonists for peripheral α1‐ and α2‐ adrenoreceptors was determined and related to their cardiovascular effects in pentobarbitone‐anaesthetized rats.
In isolated tissues, presynaptic α2‐ and postsynaptic α1‐adrenoreceptor activity was determined on the rat vas deferens and anococcygeus muscle respectively. Xylazine, guanabenz, guanoxabenz and guanfacin were more selective, whilst lofexidine, tiamenidine, naphazoline, oxymetazoline and St 91 were less selective than clonidine for presynaptic α2‐adrenoreceptors.
The anococcygeus muscle of the pithed rat was used to determine the α‐adrenoreceptor selectivity of the compounds in vivo. The selectivities were similar to those obtained in vitro.
Following intravenous administration to pentobarbitone‐anaesthetized rats guanabenz and guanfacin caused small transient pressor responses and a prolonged secondary hypotension. In contrast oxymetazoline and St 91 produced marked initial pressor responses and the secondary reduction in blood pressure was absent. Clonidine and tiamenidine produced marked initial pressor responses followed by secondary hypotensive effects. All compounds reduced heart rate.
Intracerebroventricular (i.c.v.) administration of clonidine, guanabenz and guanfacin elicited falls in blood pressure and heart rate. In contrast blood pressure was either unaffected or elevated following i.c.v. administration of St 91, oxymetazoline and tiamenidine.
It is concluded that in the normotensive rat, central α2‐adrenoreceptors play a major role in the hypotensive effects of clonidine and related compounds.
RELEASE OF 3H‐ADRENALINE FROM AN ISOLATED INTACT PREPARATION OF THE RABBIT ADRENAL GLAND: NO EVIDENCE FOR RELEASE MODULATORY α‐ADRENORECEPTORS
Authors: COLLETT A. R. , STORY D. F. 
Published: January 2008

The possibility that catecholamine secretion from the rabbit adrenal gland is subject to modulation by a mechanism involving α‐adrenoreceptors was investigated in an isolated preparation of the gland.
Intact left adrenal glands from the rabbit were perfused with Krebs‐Henseleit solution through their vasculature. The adrenal catecholamine stores were radiolabelled with 3H‐adrenaline and subsequently, efflux of the radiolabel was elicited by stimulation of an attached segment of splanchnic nerve (60 s at 5 Hz). In some experiments, efflux of radiolabel was elicited by perfusion with potassium‐enriched Krebs‐Henseleit solution (30 mM).
Radioactivity released in response to nerve stimulation was accounted for almost entirely by (3H)‐adrenaline. Stimulation‐induced (S‐I) efflux was abolished by 0.1 μM tetrodotoxin and by omission of calcium from the perfusion medium and was reduced by approximately 55% by 100 μM hexamethonium.
S‐I efflux was enhanced to approximately 150% of control S‐I efflux in the presence of 10μM phenoxybenzamine; however, 3 μM phentolamine and yohimbine in concentrations of 0.1 and 1.0 μM had no effect; in a higher concentration (10μM) yohimbine reduced S‐I efflux by approximately 50%. It is likely that the effect of phenoxybenzamine in enhancing S‐I efflux is due to blockade of reuptake of 3H‐adrenaline since cocaine (30 μM) enhanced release to a similar extent.
S‐I efflux was not altered in the presence of the α‐adrenoreceptor agonists noradrenaline (0.1 μM), clonidine (1 μM) or oxymetazoline (10 μM).
Release of radiolabel evoked by perfusion with 30 mM potassium solution was unaltered in the presence of phentolamine (3 μM) or clonidine (1 μM).
These findings do not support the existence in the rabbit adrenal gland of a mechanism involving α‐adrenoreceptors through which catecholamine secretion may be modulated.
FUNCTIONAL ROLE OF CARDIAC PRESYNAPTIC α2‐ADRENORECEPTORS IN THE BRADYCARDIA OF α‐ADRENORECEPTOR AGONISTS IN PENTOBARBITONE‐ AND URETHANE‐ANAESTHETIZED NORMOTENSIVE RATS
Authors: DE JONGE A. , SANTING P. N. , TIMMERMANS P. B. M. W. M. , VAN ZWIETEN P. A. 
Published: January 2008

The relative potencies of 6 α‐adrenoreceptor agonists, with differing physicochemical properties, at cardiac presynaptic α‐adrenoreceptors were determined by measuring their ability to reduce the tachycardia produced by stimulation of the cardiac sympathetic nerves in pithed rats. The compounds studied were clonidine, B‐HT 933 (azepexole), oxymetazoline, St 91, naphazoline and DPI.
The bradycardia produced by the same compounds in bilaterally vagotomized, urethane‐ or pento‐barbitone‐anaesthetized normotensive rats were also compared. The relative order of presynaptic potency appeared similar to that observed for the bradycardic activity of the compounds in urethane‐ and pento‐barbitone‐anaesthetized rats. In pentobarbitone‐anaesthetized rats all compounds evoked a maximal effect of 18–20% reduction in heart rate. In urethane‐anaesthetized rats, however, a difference was observed between clonidine and azepexole on the one hand and oxymetazoline, St 91, naphazoline and DPI on the other hand. The former induced a 20–22% reduction in cardiac frequency, whereas the latter diminished heart rate by 10–16% only. In vagotomized, bilaterally adrenalectomized, urethane‐anaesthetized rats, clonidine, St 91, naphazoline and azepexole evoked a 25% reduction in heart rate, whereas a 20% reduction was observed for DPI and oxymetazoline.
A radio‐enzymatic determination of plasma catecholamines demonstrated that under urethane‐anaesthesia plasma adrenaline concentrations were significantly elevated over the values observed in pentobarbitone‐anaesthetized rats. This rise in plasma adrenaline was related to the amount of urethane used. In urethane‐anaesthetized, bilaterally adrenalectomized rats, plasma adrenaline was not significantly elevated.
These findings demonstrate the involvement of cardiac presynaptic α2‐adrenoreceptors in the acute bradycardia, evoked by the α‐adrenoreceptor agonist upon intravenous application to pentobarbitone‐anaesthetized, normotensive rats. In urethane‐anaesthetized rats, however, the functional role of the cardiac presynaptic α2‐adrenoreceptors may be obscured as a result of the high plasma adrenaline levels observed in these animals.
PRESYNAPTIC DOPAMINE RECEPTORS MEDIATE THE INHIBITORY ACTION OF DOPAMINE AGONISTS ON STIMULATION‐EVOKED PRESSOR RESPONSES IN THE RAT
Authors: CLAPHAM J. C. , HAMILTON T. C. 
Published: January 2008

1 The effects of the dopamine agonists TL‐99, M‐7 (N, N‐dimethyl analogues of aminotetralins) and N, N‐dinpropyldopamine (NNPD) on stimulation‐evoked pressor responses and tachycardia in pithed Sprague‐Dawley rats were investigated when pressor responses to the compounds per se had subsided. Various antagonists were used to characterise the effects of the dopamine agonists.2 M‐7 (3 μg/kg i.v.) and NNPD (1 mg/kg i.v.), but not TL‐99 (1–30 μg/kg i.v.), inhibited pressor responses evoked by low frequency electrical stimulation of the spinal cord in the pithed rat.3 M‐7 (3 μg/kg i.v.), but neither NNPD (1 mg/kg i.v.) nor TL‐99 (1–30 μg/kg), inhibited tachycardia evoked by low frequency electrical stimulation of the spinal cord in the pithed rat.4 The inhibition of stimulation‐evoked pressor responses by M‐7 and NNPD was prevented by pimozide, metoclopramide and sulpiride but not by yohimbine, atropine, cimetidine or propranolol.5 The inhibition of stimulation‐evoked tachycardia by M‐7 was prevented by yohimbine (and to a certain extent by sulpiride) but not pimozide, metoclopramide, atropine or cimetidine.6 Pressor responses elicited by TL‐99, M‐7 and NNPD were selectively antagonised by yohimbine, but not by prazosin, indicating that these responses were mediated by stimulation of vascular postsynaptic α2‐adrenoreceptors.7 This study demonstrates that, in the rat, presynaptic dopamine receptors exist on sympathetic pre‐ or postganglionic nerve endings to blood vessels, but not on sympathetic pre‐ or postganglionic nerve endings to the heart, where inhibition by M‐7 of stimulation‐evoked tachycardia is mediated by stimulation of presynaptic α2‐adrenoreceptors.
POSITIVE CHRONOTROPIC RESPONSES PRODUCED BY α‐ADRENORECEPTORS IN THE PITHED RAT
Authors: TUNG L‐H. , RAND M. J. , DRUMMER O. H. , LOUIS W. J. 
Published: January 2008

Phenylephrine (1–100 γg/kg, intravenously) produced dose‐dependent increases in heart rate and blood pressure in the pithed rat.
The positive chronotropic response to phenylephrine (10 μg/kg) was reduced in a dose‐dependent manner by propranolol (0.01–0.3 mg/kg), but higher doses of propranolol (up to 3 mg/kg) did not reduce the response by more than about 50%. The residual response was virtually abolished by phentolamine (0.3 mg/kg) or prazosin (3 μg/kg). Labetalol (3 mg/kg) which has both α‐ and β‐blocking activity, also abolished the positive chronotropic response.
The pressor response to phenylephrine (1–30 μg/kg) was enhanced by propranolol (1 mg/kg) and abolished by phentolamine (1 mg/kg) and prazosin (30 μg/kg). Labetalol (3 mg/kg) reduced the response to phenylephrine by 73%.
Propranolol (0.3 mg/kg) completely blocked the chronotropic and vasodepressor effects of isoprenaline (0.1 μg/kg).
It is concluded that phenylephrine acts on both α1‐ and β1‐adrenoreceptors to produce an increase in heart rate, on α1‐adrenoreceptors to produce vasoconstriction and on β2‐adrenoreceptors to produce vasodilation. This latter effect is usually masked by the predominant vasoconstrictor action.
ANALYSIS OF THE ANTAGONISM BY PRAZOSIN OF NORADRENALINE AND PHENYLEPHRINE INDUCED CONTRACTIONS OF THE RAT ANOCOCCYGEUS MUSCLE*
Authors: ADENEKAN O. O. , TAYO F. M. 
Published: January 2008

Blockade of α‐adrenoreceptors was analyzed with prazosin in the rat anococcygeus muscle contracted with noradrenaline (NA) and phenylephrine (PHE).
Prazosin (1.1 times 10–8– 8.8 times 10–7M) competitively blocked phenylephrine‐induced contractions (pA2= 8.93 ± 0.04, slope = 0.85 ± 0.07) whilst its antagonism of NA was non‐competitive (pA2= 8.45 ± 0.04, slope = 0.46 ± 0.03).
At higher concentrations, (1.76 times 10–5– 5.28 times 10–6M) prazosin competitively antagonized NA‐induced contractions (pA2= 7.58 ± 0.11, slope = 0.93 ± 0.09).
Phentolamine also reduced the effect of NA competitively (pA2= 8.11 ± 0.09, slope = 0.82 ± 0.26).
It is concluded that low concentrations of prazosin selectively blocked an α1‐adrenoreceptor component of NA‐mediated response whilst higher concentrations of prazosin non‐selectively blocked both α1‐ and α2‐adrenoreceptors.
DESENSITIZATION OF β‐ADRENORECEPTORS IN GUINEA‐PIG TRACHEA: A PROSTAGLANDIN MEDIATED PHENOMENON
Authors: BERTI F. , DAFFONCHIO L. , FOLCO G. C. , OMINI C. , VIGANO T. 
Published: January 2008

The formation and release of PGE2‐like material (PGE2‐lm) from guinea‐pig isolated trachea and human bronchi following relaxation with isoprenaline (I) was investigated.
When airway smooth muscle precontracted with pilocarpine is relaxed by I, PGE2‐lm is released in the bathing fluid. Under conditions of β‐adrenoreceptor desensitization, a greater amount of PGE2‐lm is formed and the responsiveness of guinea‐pig tracheal spirals to cumulative doses of I is diminished.
Inhibition of cyclo‐oxygenase with indomethacin does not modify the relaxation induced by I but prevents the occurrence of refractoriness to I as well as formation and release of PGE2‐lm. Addition of exogenous PGE2 to guinea‐pig tracheas which were treated with indomethacin is able to restore the capacity of I to cause tachyphylaxis.
It is concluded that PGE2 which does not mediate the relaxation induced by I in airway smooth muscle, is responsible for the onset of desensitization of the β‐adrenoreceptor.
MODULATION BY β‐ADRENORECEPTORS OF SPONTANEOUS CONTRACTIONS OF RAT URINARY BLADDER
Authors: MAGGI C. A. , MELI A. 
Published: January 2008

Propranolol (0.1 mg/kg i.v.) but not metoprolol (0.2 mg/kg i.v.) pretreatment increased the spontaneous motility triggered by progressive filling of rat urinary bladder without a concomitant effect on bladder capacity, except at high filling volumes. Compared to controls, the spontaneous motility of urinary bladder in propranolol pretreated rats displayed a higher frequency, indicating the existence of a tonic sympathetic inhibition.
β‐adrenoreceptor stimulation by isoprenaline (0.1–10 μg/kg i.v.) or terbutaline (0.1–1 mg/kg i.v.) in vivo produced a dose dependent inhibition of bladder spontaneous motility which was antagonized by propranolol (0.1 mg/kg i.v.) but not by metoprolol (0.2 mg/kg i.v.). Propranolol (0.2 mg/kg i.v.) pretreatment did not antagonize the inhibition of bladder motility produced by intravenous papaverine (0.5 mg/kg).
Propranolol (0.1 mg/kg i.v.) significantly antagonized the isoprenaline‐induced tachycardia (β1 mediated) and fall in diastolic blood pressure (β2 mediated) while metoprolol (0.2 mg/kg i.v.) antagonism was confined to β1 mediated responses.
Isoprenaline (0.25–1.5 μM) inhibited in a concentration dependent manner field stimulation induced contractions of rat detrusor muscle strips as did tetrodotoxin (0.5 μM). Hexamethonium (50 μM) had no inhibitory effect.
Our in vivo findings support the view that β2‐adrenoreceptors are responsible for modulating bladder motility mainly by suppressing the onset of spontaneous contractions.
A COMPARISON OF THE MUSCARINIC ANTAGONIST ACTIONS OF PANCURONIUM AND ALCURONIUM
Authors: DALTON D. W. , TYERS M. B. 
Published: January 2008

In the pithed rat, muscarine (2.5–10μg/kg i.v.) normally produced bradycardias, but tachycardias were seen in the presence of pancuronium (0.1–1.0mg/kg i.v.) and alcuronium (0.1–5.0mg/kg i.v.).
The tachycardia was probably a result of muscarinic receptor stimulation, because it was antagonized by atropine (10μg/kg i.v.) and pirenzepine (10–30μg/kg i.v.). The location of these muscarinic receptors is probably within the sympathetic ganglia since the tachycardias were inhibited by pretreatment with propranolol (1mg/kg i.v.) or reserpine (5mg/kg i.p. 24 h prior to study).
In the rat isolated atria preparation, pancuronium was 86 times more potent as an antagonist of the effects of muscarine than in the rat isolated superior cervical ganglion. The mechanism of action in both tissues may be non‐competitive.
Pancuronium selectivity antagonized atrial inhibitory muscarinic responses compared to excitatory muscarinic responses in sympathetic ganglia in the rat.