bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADRENORECEPTOR‐MEDIATED RESPONSES IN THE ISOLATED PORTAL VEIN OF THE HYPOTHYROID RAT
Authors: LEE YOONG YAN , STORY MARGOT E. , ISHAC E. J. , PENNEFATHER JOCELYN N. , HANDBERG GWYNNETH M. 
Published: January 2008

1 The effect of hypothyroidism, induced by methimazole, upon the respone of the isolated portal vein of the rat to adrenoreceptor agonists and antagonists, to angiotensin II and to papaverine has been investigated.2 The positions and maxima of log dose‐response curves, to the vasoconstrictor agonists, noradrenaline and angiotensin II, and to the vasodilator agonists isoprenaline and papaverine, were unaffected by methimazole treatment.3 The α‐adrenoreceptor antagonist phentolamine competitively inhibited the effects of noradrenaline to a similar extent in preparations from control and hypothyroid animals. The competitive antagonism of isoprenaline by the β‐adrenoreceptor antagonist propranolol was similarly unaffected by hypothyroidism.4 These results taken together indicate that hypothyroidism is without significant effect upon either the properties of postjunctional α‐ β‐adrenoreceptors in the rat portal vein, or upon the reactivity of this blood vessel to the vasoactive agonists studied.
PHARMACOLOGY OF POSTSYNAPTIC α‐ADRENORECEPTORS IN THE MOUSE ANOCOCCYGEUS MUSCLE
Authors: GIBSON A. , YU O. 
Published: January 2008

1 The α‐adrenoreceptor agonists noradrenaline (NA), methoxamine, phenylephrine, naphazoline, oxymetazoline, and xylazine produced contractions of the mouse anococcygeus muscle. All were full agonists.2 Cocaine (2 μM) increased the pD2 values of NA and phenylephrine. 6‐hydroxydopamine pretreatment increased the pD2 values of NA, phenylephrine, and xylazine. After both procedures the order of potency of the agonists was oxymetazoline > naphazoline > NA > phenylephrine > methoxamine > xylazine.3 The order of potency of antagonists against all six agonists was prazosin > phentolamine > yohimbine. However, from differences in the pA2 values and slopes of the Schild plots of the antagonists it was possible to distinguish three distinct groups of agonists: the phenylethylamines; the imidazolines; and the thiazine derivative xylazine.4 The results suggest that the postsynaptic α‐adrenoreceptor of the mouse anococcygeus muscle may be broadly classified as α1. However, there may be at least three drug recognition sites on the receptor which interact with agonists of differing chemical structure.
ABSENCE OF A CHOLINERGIC COMPONENT IN NORADRENERGIC TRANSMISSION IN THE CERVICAL SYMPATHETIC NERVE OF THE RAT
Authors: MERCHANT S. J. , HUGHES I. E. 
Published: January 2008

1 In rats anaesthetised with chloralose and pentobarbitone, frequency‐dependent tachycardia and contraction of the ipsilateral inferior eyelid occurred when the intact right cervical sympathetic nerve was stimulated.2 After successive doses of 5, 12.5 and 30 μg.kg‐1 neostigmine sulphate (i.v.) a progressive reduction was seen in the tachycardias to low frequency stimulation (0.2 to 2 Hz) but either no effect, or an augmentation after 30 μg.kg‐1, was evident at higher frequencies (up to 20 Hz). Atropine sulphate (i.v., 100 μg.kg‐1) abolished the augmentatory effect of neostigmine on the high‐frequency responses and offset partially the depressant effect of neostigmine on the responses to 0.2 and 0.5 Hz. By contrast, contractions of the eyelid were unaltered by neostigmine and atropine.3 Reserpinised rats (8 mg.kg‐1 i.p., 24 h earlier) were quite refractory to stimulation and remained so after neostigmine and atropine.4 The effectiveness of neostigmine (enhancing responses) and atropine (inhibiting them) was demonstrated on endogenous acetylcholine (ACh) by measuring bradycardia to right efferent vagal stimulation, and on exogenous ACh by measuring inferior eyelid retraction in both reserpinised and control rats. These groups were equally sensitive to either ACh or noradrenaline and cocaine potentiated the tachycardia to nor‐adrenaline in both groups.5 Propranolol reduced the tachycardia and phentolamine the eyelid contraction induced by sympathetic nerve stimulation.6 The findings offer no support to a theory implying an obligatory cholinergic‐link in noradrenergic transmission.
INCREASED α2‐ADRENORECEPTOR MEDIATED VASCULAR CONTRACTION IN DIABETIC RATS
Authors: SCARBOROUGH N. L. , CARRIER G. O. 
Published: January 2008

Contractile responses of aortic ring preparations from control and diabetic rats to nonselective (noradrenaline) and selective α1‐(phenylephrine) and α2‐ (clonidine) adrenoreceptor agonists were examined to determine the contribution of these receptor subtypes to the response.
Aortae from diabetic rats were more responsive to noradrenaline compared to age‐matched control rats. There was no difference between contractile responses of aortae from control and diabetic rats to phenylephrine, whereas clonidine‐induced contractions were enhanced in aortae from diabetic rats.
Dependence of clonidine‐induced contractions on extracellular calcium availability was determined. Each of the methods used indicated increased dependency of aortae from diabetic rats on extracellular calcium availability for clonidine‐induced contractile force generation.
These data indicate that the increased noradrenaline‐induced responsiveness of aortae from diabetic rats may be attributed to an increased α2‐adrenoreceptor component of the contractile response. It is also concluded that the α2‐adrenoreceptor mediated contraction is primarily dependent upon extracellular calcium. From this we suggest that the increased contractile responsiveness of aortae from diabetic rats to α2‐adrenoreceptor stimulating drugs may be related to an altered coupling mechanism between the α2‐adrenoreceptors and the calcium ion channels or due to a change in membrane permeability as a result of the disease process.
THE INHIBITORY EFFECT OF CLONIDINE ON THE OESTROGEN‐PRIMED RAT ISOLATED UTERUS
Authors: GOYAL R. K. , DAVE K. C. , VERMA S. C. 
Published: January 2008

The investigation was undertaken to study the mechanism of the inhibitory effects of clonidine on the oestrogen‐primed rat isolated uterus.
Clonidine produced dose‐dependent relaxations of the rat isolated uterus which were competitively blocked by yohimbine but not by prazosin.
Metiamide, a specific H2‐histamine receptor antagonist, inhibited clonidine‐induced responses only at a high concentration (1.0 times 10‐6M).
Propranolol, a β‐adrenoreceptor antagonist produced competitive antagonism of the clonidine responses.
Like clonidine, noradrenaline also produced dose dependent relaxations of the rat isolated uterus. The responses to noradrenaline were not antagonized by either prazosin or yohimbine but were competitively antagonized by propranolol.7 It is concluded that clonidine inhibits the uterus via an action on α2‐adrenoreceptors and possibly also to a lesser extent on H2‐histamine receptors, leading ultimately to release of noradrenaline from endogenous stores which causes relaxation by acting on β‐adrenoreceptors.
ADRENERGIC INFLUENCES ON THE SPINAL CARDIOVASCULAR NEURONES
Authors: PANT K. K. , TANGRI K. K. , BHARGAVA K. P. 
Published: January 2008

In cervical spinal cord transected and bilaterally vagotomized dogs, intrathecal (i.t.) injection of clonidine decreased the resting heart rate and mean arterial pressure (MAP) while isoprenaline increased the heart rate. The clonidine induced bradycardia and hypotension were antagonized by piperoxan pretreatment. Similarly, the isoprenaline induced tachycardia was antagonized by pretreatment (i.t.) with atenolol. Intrathecal atenolol per se decreased the heart rate and MAP while piperoxan had no effect.
The post‐coronary artery ligation cardiac arrhythmia, in the cervical spinal cord transected and bilaterally vagotomized dogs, was inhibited by clonidine, phenylephrine and methoxamine and facilitated by isoprenaline.
β‐Adrenoreceptor antagonists propranolol, atenolol and acebutolol, given intrathecally, inhibited while piperoxan facilitated the cardiac arrhythmia.
The clonidine and isoprenaline induced changes in the arrhythmia were antagonized by i.t. pretreatment with piperoxan and atenolol respectively.
It appears that the α‐adrenoreceptors are inhibitory while β‐adrenoreceptors are facilitatory for spinal control of heart rate and blood pressure and for post‐coronary artery ligation cardiac arrhythmia.
SELECTIVE STIMULATION OF VASCULAR POSTJUNCTIONAL α1‐ADRENORECEPTORS BY (‐)‐AMIDEPHRINE IN RATS AND CATS
Authors: MATHY MARIE‐JEANNE , DOODS H. N. , THOOLEN M. J. M. C. , WILFFERT B. , DE JONGE A. , TIMMERMANS P. B. M. W. M. , VAN ZWIETEN P. A. 
Published: January 2008

The vasopressor and chronotropic responses of (‐)‐amidephrine and the receptor types involved were studied in pithed rats of different strains and in pithed cats.
The increase in diastolic pressure of pithed rats after i.v. administration of (‐)‐amidephrine was not influenced by pretreatment with propranolol (1 mg/kg, i.v.), reserpine (2 times 5mg/kg in 48 h i.p.) or yohimbine (1 mg/kg, i.v.), but was strongly antagonized by prazosin (0.1 mg/kg, i.v.). In pithed cats, the pressor responses were antagonized by prazosin (1 mg/kg, i.v.) but much less so by yohimbine (1 mg/kg, i.v.).
(‐)‐Amidephrine elicited minor positive chronotropic responses in pithed rats and pithed cats. This tachycardia was not influenced by propranolol (1 mg/kg, i.v.) but was abolished by prazosin (0.1 – 1.0 mg/kg).
The results show that (‐)‐amidephrine acts as a selective agonist at vascular postjunctional α‐adrenoreceptors in pithed rats and pithed cats. The positive chronotropic effects are attributable to stimulation of α‐adrenoreceptors in the heart.
PHARMACOLOGICAL CHARACTERIZATION OF α‐ADRENORECEPTOR SUBTYPES IN RAT ISOLATED THORACIC AORTA
Authors: HAMED A. T. , JOHNSON T. D. , CHARLTON K. G. , CLARKE D. E. 
Published: January 2008

The subtype of α‐adrenoreceptor mediating contraction in rat isolated thoracic aorta was classified pharmacologically using preferential agonists and antagonists, and by utilizing mixed agonist and antagonist interactions.
Noradrenaline was 8 to 10‐times more potent at contracting the aorta than phenylephrine and both agonists were about 1000 and 10,000‐fold respectively more potent than azepexole (a preferential α2,‐agonist).
Prazosin (a preferential α1,‐antagonist) inhibited the dose‐response curves to noradrenaline and phenylephrine 100 and 1000‐times respectively more effectively than either phentolamine or rauwolscine (a preferential α2‐antagonist). Furthermore, prazosin (5 times 10‐9M). completely abolished contractions elicited by a single concentration of azepexole (3 times 10‐4M).
In mixed antagonist studies, rauwolscine (5 times 10‐7M) failed to shift the dose‐response curves to nor‐adrenaline and phenylephrine obtained in the presence of prazosin (5 times 10‐9M).
In mixed agonist experiments, azepexole (3 times 10‐4M) acted as a partial antagonist toward phenylephrine‐induced contractions.
The results suggest that the α‐adrenoreceptor of the rat thoracic aorta is predominantly, if not exclusively, of the α1‐subtype.
β‐ADRENORECEPTOR‐MEDIATED MODULATION OF VASOCONSTRICTION IN RAT ISOLATED PERFUSED MESENTERIC ARTERIES
Authors: BORKOWSKI K. R. , PORTER M. 
Published: January 2008

Pressor responses to bolus injections of noradrenaline (NA) were studied, in the isolated perfused rat mesenteric arterial bed, in the presence of β‐adrenoreceptor agonists and antagonists, in an attempt to identify a possible β‐adrenoreceptor mediated modulation of catecholamine‐induced vasoconstrictor effects.
NA‐induced responses were potentiated in the presence of timolol and (‐)propranolol and suppressed in the presence of (‐)isoprenaline; (+)isoprenaline was less effective against the NA‐induced responses.
Timolol attenuated the effects of (‐)isoprenaline on NA‐induced responses but not those of the stereoisomer (+)isoprenaline.
It is concluded that the NA‐induced pressor effect in the rat mesenteric vasculature is the net result of vasoconstrictor α‐ and vasodilator β‐adrenoreceptor activation and that the interaction of the two opposing adrenoreceptor‐mediated effects represents a ‘physiological antagonism’.
EFFECTS OF AMITRIPTYLINE, DESIPRAMINE AND MIANSERIN ON NORADRENERGIC TRANSMISSION IN THE RAT ISOLATED RIGHT VENTRICLE
Authors: BRADLEY LYNN , DOGGRELL SHEILA A. 
Published: January 2008

The effects of amitriptyline, desipramine and mianserin on the accumulation of radioactivity from [3H]‐noradrenaline, and on the subsequent spontaneous and field stimulation‐evoked outflow of radioactivity have been investigated in the rat isolated right ventricle. In addition the effect of these agents on contractions produced by isoprenaline or by field stimulation are reported.
Amitriptyline, desipramine (both at ≥ 10‐8M) and mianserin at ≥ 10‐7M inhibited the accumulation of radioactivity from [3H]‐noradrenaline.
The decline in the spontaneous outflow of radioactivity, following loading of the tissue with [3H]‐noradrenaline, was not altered by amitriptyline, desipramine or mianserin.
Rauwolscine, amitriptyline, desipramine and mianserin (all at 10‐6M) reduced or reversed the decline in outflow of radioactivity evoked by field stimulation at 5 Hz. Desipramine had no additional effects in the presence of cocaine (10‐5M) and amitriptyline and mianserin had no further effect in the presence of cocaine and rauwolscine. The effect of desipramine probably represents inhibition of neuronal uptake and that of amitriptiyline and mianserin blockade of neuronal uptake and prejunctional α2‐adrenoreceptors.
The rate of beating in the presence of isoprenaline (10‐6M) was reduced by amitriptyline (10‐7M), desipramine (10‐6M) and mianserin Higher concentrations of the antidepressants greatly reduced or abolished the rate and force of beating in the presence of isoprenaline.
The force of contractions evoked by field stimulation at 5Hz was increased to a small extent by amitriptyline, desipramine and mianserin at 10‐7M and reduced by the antidepressants at 10‐5M. It is suggested that in the rat isolated right ventricle, the inability of antidepressants to potentiate contractile responses to field stimulation to a great extent as a consequence of blocking neuronal uptake and prejunctional α‐adrenoreceptors is due to a decreased excitability of the postjunctional β‐adrenoreceptors.
DOCA‐SALT INDUCED MYOCARDIAL SENSITIZATION TO VENTRICULAR FIBRILLATION BY ISOPRENALINE IN RATS. ROLE OF THE AUTONOMIC NERVOUS SYSTME
Authors: HEALY C. , GUIDER G. 
Published: January 2008

The possible role of the autonomic nervous system in the development of myocardial sensitization to isoprenaline produced by DOCA‐salt pretreatment was evaluated in bilaterally unanaesthetized rats subject to chronic ganglionic blockade with chlorisondamine or hexamethonium and to treatment with 6‐hydroxydopamine.
Isoprenaline produced ventricular fibrillation and death in rats pretreated for 6 days wirh DOCA (20 mg pellet, s.c.) and 0.9% saline. The incidence of mortality was dose dependent and was 76.6% with 150 pgfkg of isoprenaline.
Adrenalectomy did not alter the mortality rate. The combination of adrenalectomy with concurrent chronic ganglionic blockade significantly decreased the incidence of mortality and delayed the time of death.
In contrast, 6‐hydroxydopamine treatment and adrenalectomy did not alter the incidence of mortality nor time of death.
No differences in myocardial noradrenaline turnover were detected in rats susceptible and non‐susceptible to death in ventricular fibrillation.
We conclude that myocardial sensitization to isoprenaline induced by DOCA‐salt requires a neurogenic component, which is not, however, manifested by changes in myocardial noradrenaline turnover.
COMPARISON OF THE EFFECTS OF LABETALOL AND SCH 19927, THE RIR ISOMER OF LABETALOL, ON THE RAT ISOLATED RIGHT VENTRICLE AND AORTA
Authors: DOGGRELL SHEILA A. , HUGHES E. W. 
Published: January 2008

The effects of labetalol and its RIR isomer, SCH 19927, on the accumulation of radioactivity from [3H]‐noradrenaline, and on the subsequent spontaneous and nerve‐evoked outflow of radioactivity have been investigated in the rat isolated right ventricle. In addition, the effect of these agents on the contractions of the electrically‐driven rat right ventricle to isoprenaline and of the rat isolated aorta to phenylephrine and 5‐hydroxytryptamine are reported.
Labetalol and SCH 19927 (both at 10‐6M) inhibited the accumulation of radioactivity from [3HJ‐noradrenaline by 26 and 37%, respectively.
The spontaneous outflow of radioactivity, following loading of the ventricle with [3H]‐noradrenaline, was increased by labetalol and SCH 19927 (both at 1OP6M) by a cocaine and idazoxan‐insensitive mechanism.
The nerve‐evoked outflow of radioactivity was increased by labetalol and SCH 19927 (both at 10‐6M). The ability of labetalol and SCH 19927, to increase nerve‐evoked outflow was maintained in the presence of cocaine (lO‐5M) or idazoxan (10‐7M) but reversed in the presence of cocaine and idazoxan. It is suggested that labetalol and its RIR isomer act both to inhibit neuronal uptake of noradrenaline and as antagonists at prejunctional orz‐adrenoreceptors. Labetalol and SCH 19927 reduced the contractile responses associated with the nerve‐evoked outflow of radioactivity probably mainly by acting as antagonists at postjunctional p1 ‐adrenoreceptors.
The contractile responses of the electrically‐driven rat right ventricle to isoprenaline were inhibited by labetalol and SCH 19927. SCH 12297 (pA2 = 8.9) was 4 times more potent than labetalol (pA2 = 8.3) as a p1‐adrenoreceptor antagonist. The ability of labetalol and SCH 19927 at 2 10‐7M to depress maximal responses to isoprenaline may represent membrane stabilizing activity.
The contractile responses of rat aorta to phenylephrine were inhibited by labetalol and SCH 19927. Labetalol (pA2 = 7.5) was 4X more potent than SCH 19927 (pA2 = 6.9) as an al‐adrenoreceptor antagonist. SCH 19927 and labetalol had no effect on contractile responses to 5‐hydroxytryptamine.
INFLUENCE OF URAPIDIL ON α‐ AND β‐ADRENORECEPTORS IN PITHED RATS
Authors: SANDERS K H. , KILIAN U. , KOLASSA N. , SCHOETENSACK W. 
Published: January 2008

The interaction of urapidil with pre‐ and postsynaptic a‐adrenoreceptors and with postsynaptic 8‐ adrenoreceptors was studied in pithed normotensive rats and compared to the effects of clonidine, prazosin, and atenolol.
I.v. injection of urapidil did not substantially change blood pressure, while clonidine raised blood pressure.
Urapidil dose‐dependently antagonized the pressor effects of the al‐agonist L‐phenylephrine (pDR2 6.8) and of the a2‐agonist azepexole (pDR2 5.2). Compared to urapidil, prazosin was a more potent antagonist of phenylephrine at postsynaptic vascular al‐adrenoreceptors (pDR2 8.7) and of azepexole at a2‐adrenoreceptors (pDR2 5.6).
Urapidil inhibited the tachycardia produced by discontinuous or continuous electrical stimulation of the thoracic spinal outflows (IDSo 4.8 and 27.2 Fmol/kg, respectively). In contrast to the inhibitory action of clonidine (IDSo 0.039 and 0.023 pmolikg, respectively), the inhibition by urapidil was not reversed by the selective a2‐antagonist rauwolscine (10 pmolikg). Prazosin did not change stimulation‐evoked tachycardia but atenolol caused pronounced inhibition (IDS0 0.158 prnol/kg, discontinous stimulation).
Umpidi! dcse‐APnendently –r antagerincd the tachycardic effect of isoprenaIinP nt g:‐adrennreceptors (pDR2 5.1) but also exhibited intrinsic activity by increasing basal heart rate (maximum effect of urapidil was 30% of that of isoprenaline). Urapidil did not change the vasodilatory P2‐adrenoreceptor‐mediated effect of isoprenaline.
The results suggest that urapidil is an antagonist at postsynaptic vascular el‐ and a2‐adrenoreceptors, with a greater potency against al‐adrenoreceptors. An agonistic interaction of urapidil with presynaptic a2‐adrenoreceptors could not be demonstrated in pithed rats. Instead, the inhibition by urapidil of stimulation‐evoked tachycardia could be accounted for by its bl‐adrenoreceptor antagonistic effect.
ROLE OF DOPAMINE AND α‐ADRENORECEPTORS IN THE CONTROL OF GASTRIC EMPTYING IN THE RAT: POSSIBLE INVOLVEMENT IN THE MECHANISM OF ACTION OF METOCLOPRAMIDE
Authors: COOPER S. M. , McRITCHIE B. 
Published: January 2008

The object of the study was to investigate the effects of dopamine receptor and a‐adrenoreceptor agonists and antagonists on the gastric emptying of a liquid test meal in conscious rats and the possible involvement of these receptors in the mechanism of action of metoclopramide.
The gastric emptying of a liquid test meal in conscious chronic gastric fistula rats was delayed following subcutaneous administration of either 6,7‐ADTN (1‐50 mgikg) or clonidine (0.05‐1 mgikg). Phenylephrine (0.2–10 mg/kg s.c.) had no effect on gastric emptying, suggesting that dopamine and a2‐, but not al‐adrenoreceptors may be involved in the control of gastric emptying in the rat.
Phentolamine (0.2–5 mg/kg s.c.) and prazosin (0.1–0.5 mg/kg s.c.) potentiated the delay in gastric emptying induced by 6,7‐ADTNY whilst yohimbine (1–5 mg/kg s.c.) and prazosin (0.1–0.5 mg/kg s.c.) reversed the delay in emptying induced by clonidine. All three a‐adrenoreceptor antagonists also delayed gastric emptying in the absence of agonist. Propranolol(0.2–5 mgikg s.c.) had no effect on either normal or delayed gastric emptying.
Both metoclopramide (1–10 mg/kg s.c.) and haloperidol (0.02–0.5 mgikg s.c.) reversed the 6,7‐ADTN‐induced delayed emptying but not the clonidine‐induced delayed emptying. In addition, metoclopramide (5–10 mg/kg s.c.), but not haloperidol, increased gastric emptying in the absence of agonist.
In conclusion, these results show that dopamine and a‐adrenoreceptors may be involved in the control of gastric emptying in the rat. However, it would appear that a2‐adrenoreceptors are unlikely to be involved in the mechanism of action of metoclopramide. Although there is some evidence that peripheral dopamine receptors may be involved, the fact that metoclopramide significantly increased gastric emptying in the absence of 6,7‐ADTN suggests that its dopamine receptor antagonist properties may contribute only in part towards its mechanism of action.
RELATIVE CONTRIBUTION OF DIFFERENT VASCULAR BEDS TO THE PRESSOR EFFECTS OF α‐ADRENORECEPTOR AGONISTS AND VASOPRESSIN IN PITHED RATS: RADIOACTIVE MICROSPHERE DETERMINATION
Authors: WALDRON C. J. , HICKS P. E. 
Published: January 2008

The relative fractional distribution of SICr‐labelled microspheres was evaluated in pithed rats during equieffective vascoconstrictor responses evoked by infusions of the α‐adrenoreceptor agonists methoxamine (α1‐selective), UK‐ 14,304 (α2‐selective) or vasopressin. The proportion of injected radioactive microspheres trapped in each tissue during a sustained pressor response relative to saline treated controls is considered a reflection of the degree of local vascoconstriction in the tissue analysed.
All three agonists (methoxamine, UK‐14,304 and vasopressin) decreased the number of micro‐spheres trapped in the mesentery and tail. Only methoxamine reduced the blood flow to the kidney and spleen. UK‐14,304 did not modify the number of microspheres in the sample of skeletal muscle, however, both vasopressin and methoxamine reduced the blood flow to this tissue. Vasopressin increased the counts in the lungs and particularly in the liver but decreased the number of spheres trapped in the stomach and skin. In contrast to the a‐adrenoreceptor agonists, vasopressin did not increase the number of microspheres trapped in the heart.
Since a reduction in the number of microspheres trapped in the tissue reflects a decrease in blood flow, to that organ it is reasonable to conclude that al‐adrenoreceptor stimulation increases kidney, spleen, mesentery, caudal and skeletal muscle vascular resistance, whereas a2‐adrenoreceptors appear to preferentially vasoconstrict the mesenteric and the caudal vascular beds.