bluuebunny/crossref_metadata_2025_split huggingface dataset:
AN EXAMINATION OF AUTONOMIC NERVOUS FUNCTION IN GENETICALLY DIABETIC MICE
Authors: WILSON HILARY F. , MAYER J. HEIDI , CLARKE SHARON A. , TOMLINSON D. R. 
Published: January 2008

1 This study was designed to determine whether the autonomic innervation of the heart and vas deferens in genetically diabetic mice exhibited dysfunction similar to those seen in chemically diabetic animals and diabetic patients.2 Diabetic mutant mice (outcrossed from the C57 BL/KS db/db strain) were compared with their non‐diabetic litter‐mates at age 20 to 22 weeks. Right and left atria and vasa deferentia were removed from freshly killed animals and subjected to nerve stimulation and treatment with noradrenaline (NA) or acetyl‐choline (ACh) in organ baths.3 Right atria from diabetic animals were less responsive to noradrenergic nerve stimulation than control preparations but there was no such difference between the noradrenergic responses of left atria from the two groups of mice. Both atria were hypersensitive to exogenous NA.4 Atria from diabetic mice responded to cholinergic nerve stimulation and exogenous ACh in a fashion similar to those of non‐diabetic mice. Likewise the responses of vasa deferentia to nerve stimulation were similar in the two groups. These findings are indicative of some autonomic nervous dysfunction characteristic, to an extent, of diabetes mellitus.
CHARACTERIZATION OF THE ADRENORECEPTOR ACTIVITIES OF ISOPRENALINE IN THE FIELD STIMULATED RAT VAS DEFERENS: SELECTIVE SUPERSENSITIVITY TO β2‐MEDIATED RESPONSES FOLLOWING RESERPINE TREATMENT
Authors: LOTTI V. J. , CERINO D. , KLING P. 
Published: January 2008

1 Low concentrations of isoprenaline (EC50= 45.6 nM) inhibited contractions in the isolated field stimulated rat vas deferens. This inhibitory effect was markedly attenuated by the postjunctional β2‐adreno‐receptor antagonist timolol, but not affected by the prejunctional α2 or postjunctional α1‐adrenoreceptor antagonists rauwolscine and prazosin, respectively.2 In vas deferens of rats previously treated with reserpine, the postjunctional β2‐adrenoreceptor‐mediated inhibitory response to isoprenaline was markedly potentiated.3 High concentrations of isoprenaline (EC50= 1.5 uM) also inhibited contractility in tissues in which postjunctional β2‐adrenoreceptors were maximally blocked by high concentrations of timolol. This contractile inhibition produced by isoprenaline was abolished by rauwolscine but not significantly altered by prazosin or pretreatment of the rats with reserpine indicating stimulation of prejunctional α2‐adreno‐receptors.4 Rauwolscine pretreatment unmasked an ability of isoprenaline (EC50= 17.1 juM) to produce enhancement of field stimulation‐induced contractions. This response was abolished by prazosin but was unaffected by timolol or reserpinization indicating an action upon postjunctional α1‐adrenoreceptors.5 The data indicate isoprenaline activates adrenoreceptor mechanisms in the field stimulated rat vas deferens by a direct action not dependent upon endogenous catecholamines and with an order of activity of β2>α2>α1. Pretreatment with reserpine produces rapid and selective development of supersensitivity to the postjunctional β2‐mediated inhibitory response of isoprenaline in this preparation.
THE EFFECTS OF 6‐HYDROXYDOPAMINE OR (–)‐NORADRENALINE TREATMENT IN VITRO ON NORADRENERGIC TRANSMISSION IN THE RAT ANOCOCCYGEUS MUSCLE
Authors: DOGGRELL SHEILA A. , WALDRON J. B. 
Published: January 2008

The effects of 6‐hydroxydopamine treatment in vitro for varying times on the overflow of 3H (following preloading of the tissue with (–)‐[3H]‐noradrenaline) and the accumulation of 3H from (–)‐[3H]‐noradrenaline have been investigated in the rat anococcygeus muscle. In addition the effects on contractile responses to field stimulation and to other stimulants are reported.
Following preloading of the rat anococcygeus muscle with 5 times 10‐7M (–)‐[3H]‐noradrenaline for 1 h, the overflow of 3H was increased by 6‐hydroxydopamine (1 times 10–3M). At the end of the overflow period the tissue content of 3H was reduced by 95% from tissues treated with 6‐hydroxydopamine for ≥ 30 min. The rat anococcygeus muscle accumulated 3H from a medium containing 5 times 10–8M (–)‐[3H]‐noradrenaline. The ability to accumulate 3H was reduced after incubation in 6‐hydroxydopamine for 5 min and abolished by longer incubations. These effects of 6‐hydroxydopamine probably represent depletion of endogenous (–)‐noradrenaline stores and destruction of noradrenergic neurones.
6‐Hydroxydopamine induced contractions of the rat anococcygeus that were abolished by phentolamine (1 times 10‐6M).
The excitatory contractile responses to field stimulation were reduced after exposure to 6‐hydroxy‐dopamine for 5 min and were abolished after longer exposures. 6‐Hydroxydopamine had no effect on the inhibitory response to field stimulation. The contractile responses to (–)‐noradrenaline were potentiated after 6‐hydroxydopamine.
Following 6‐hydroxydopamine treatment for 5 min the responses to tyramine were potentiated. This potentiation was probably due to the release of endogenous (–)‐noradrenaline. The responses to tyramine were reduced after longer treatments (30–120 min).
Short incubations of the anococcygeus muscle with 6‐hydroxydopamine or (–)‐noradrenaline had no effect on the subsequent responses to acetylcholine whereas after a 180 min treatment the responses were reduced. This effect was possibly due to fatigue of the muscle. Incubations with (–)‐noradrenaline for 60 min had no effect on the responses to field stimulation or to (–)‐noradrenaline. After longer pretreatments the responses were reduced. Thus after long exposures to (–)‐noradrenaline, and probably to 6‐hydroxy‐dopamine, responses may be reduced by fatigue or by desensitization at α‐adrenoreceptors.7 These results suggest that, in the rat anococcygeus muscle, a selective abolition of noradrenergic transmission was obtained by treating the tissue with 6‐hydroxydopamine for 30–60 min. The contractile responses to tyramine in this tissue may, in part, be due to a direct postjunctional action.
Reassessment of the blocking activity of prazosin at low and high concentrations on sympathetic neurotransmission in the isolated mesenteric vasculature of rats
Authors: Yamamoto R. , Cline W. H. , Takasaki K. 
Published: January 2008

1 The overflow of endogenous noradrenaline from the rat mesenteric arterial vasculature was determined along with the perfusion pressure response to periarterial nerve stimulation (PNS) (4–12 Hz).2 The PNS‐induced pressor responses were blocked by prazosin at 3x 108 M but not by prazosin at 10−6 M or the combination of prazosin at 3 × 10−8 M and yohimbine (10−7 M).3 The PNS‐induced overflow of endogenous noradrenaline was significantly augmented by prazosin at 10−6 M or the combination of prazosin at 3 × 10−8 M and yohimbine (10−7 M) but not by prazosin at 3 × 10−8 M alone.4 The PNS‐induced pressor response and endogenous noradrenaline overflow, in the absence of prazosin, were not significantly influenced by α, β‐methylene‐adenosine triphosphate (α, β‐methylene ATP) (3x10−6 M). The pressor responses to PNS which remained after prazosin at 10−6 M were abolished by pretreatment with α, β‐methylene ATP and therefore attributable to coreleased ATP.5 The pressor responses to exogenous noradrenaline were abolished by prazosin at both 3 × 10−8 M and 10−6 M.6 These results suggest that no functionally significant amount of ATP was coreleased with noradrenaline by PNS in the presence of prazosin at low concentrations which blocked only postjunctional α1‐adrenoreceptors.7 Thus, these results indicate that the effects of prazosin at high concentrations, such as 10−6 M, on sympathetic neurotransmission should not be ignored when considering the mechanisms of vasoconstrictor responses to PNS following high concentrations of prazosin.
Prostaglandin I2 and thromboxane A2production in relation to α1 and α2‐adrenoreceptor activation in the normotensive and hypertensive rat
Authors: Pipili E. , Zoumboulis G. , Maragoudakis M. E. 
Published: January 2008

1 The perfused mesenteric arterial bed (MAB) from normotensive (WKY) and hypertensive (SHR) rats was used as a model to investigate the relationship between α1 and α2‐adrenoreceptor activation and prostanoid release.2 Prostaglandin I2 (PGI2) and small amounts of thromboxane A2 (TXA2) are released from this preparation and can be monitored in the perfusate under basal and stimulated conditions.3 Noradrenaline (NA) caused a significant increase in the release of PGI2 from the MAB of both WKY and SHR. Both basal and NA‐stimulated PGI2 release were lower in the SHR, whereas pressor responses to NA were higher. Noradrenaline caused a very small increase in TXA2 release in the WKY only and the basal release of this prostanoid was again lower in the SHR.4 Prazosin, an α1‐selective antagonist (10−10, 10−9, 10−8M) was more effective in blocking pressor responses to NA in the SHR than in the WKY, did not affect the NA‐induced release of PGI2 in either group and abolished the small increase of TXA2 release in WKY.5 Rauwolscine, an α2‐selective antagonist (10−8, 10−7, 10−6 M) was more effective in reducing pressor responses to NA in the SHR than in the WKY. It abolished, from 10−7M upwards, the NA‐induced release of PGI2 in the WKY and reduced it in the SHR. The NA‐induced release of TXA2 was abolished in WKY.6 The observed differences in the effects of rauwolscine and prazosin do not correlate with the effects of these antagonists on pressor responses since both reduce the latter but only rauwolscine abolishes the stimulated PGI2 release.7 These results indicate that in the SHR, the mechanisms mediating the release of PGI2 from the MAB may be similar but not identical to those in the WKY. The observation that an increase in adrenergically induced pressor responses is not followed by an increase in PGI2 release, which is in fact reduced in the SHR, suggests a more complex regulation of this relationship which may have pathophysiological implications.
Differential regulation of cardiac α‐ and β‐adrenoceptors by the sympathetic nervous system
Authors: Chess‐Williams Russell , Doubleday Bridget , Reynolds Gavin P. 
Published: January 2008

1 The effects of depressed sympathetic function on the inotropic responses of the heart to sympathomimetic amines have been examined in rats immunized against nerve growth factor (NGF) 6 weeks prior to the isolation of cardiac tissues.2 The activity of tyrosine hydroxylase in cervical sympathetic ganglia and the levels of noradrenaline in ventricular tissue were significantly reduced in NGF‐immunized rats.3 Left atria and papillary muscles from NGF‐immunized rats were supersensitive to the β‐adrenoceptor agonist isoprenaline when compared with controls.4 The responses of cardiac tissues to the α‐adrenoceptor agonist phenylephrine were unaffected by immunization.5 These results support the hypothesis that cardiac β‐ but not α‐adrenoceptor sensitivity is regulated by the sympathetic nervous system.
Spectral analysis of blood pressure and heart rate variability in response to stress from air‐jet in the Lyon rat
Authors: Blanc Jocelyne , Grichois Marie‐Laure , Vincent Madeleine , Elghozi Jean‐Luc 
Published: January 2008

1 Power spectral analysis of the frequency of wave‐forms of blood pressure and heart rate was used to characterize short‐term fluctuations of these parameters in three strains of conscious Lyon rat, normotensive (LL and LN) and hypertensive LH.2 A mild stress produced by means of a jet of air elicited blood pressure rises, associated with tachycardia. This response was of similar magnitude in the three strains. The stressor amplified the medium frequency (195–605 mHz) Mayer waves of blood pressure and heart rate which are under autonomic control.3 Clonidine (10 μg kg−1 i.v.) lowered blood pressure and heart rate and dramatically reduced the amplitude of blood pressure and heart rate oscillations in the frequency region of 195–605 mHz.4 A jet of air applied after clonidine administration led to blood pressure rise associated with tachycardia and enhanced oscillations in the 195–605 mHz region.5 These results indicate that in Lyon normotensive and hypertensive rats, a mild emotional stressor elicits blood pressure and heart rate rises associated with spectral modifications reflecting sympathetic hyperactivity. Clonidine lowers blood pressure and heart rate and reduces their related variabilities. This effect is more pronounced in LH rats than in their normotensive controls. Clonidine appears to reduce the autonomic response to stress as indicated by the medium frequency oscillations.
Opiate and opiate antidiarrhoeal drug action on rat isolated intestine
Authors: Coupar I. M. , Luca A. De 
Published: January 2008

1 Stimulation of segments of rat jejunum (2.5, 5, 10, 20 and 40 Hz for 8 s) and ileum (10 Hz) resulted in a fast atropine‐sensitive contraction during stimulation and a non‐cholinergic after‐contraction. Stimulation of segments with single pulses at 0.1 Hz had no effect. The colon (10 Hz) usually responded only with single large atropine‐sensitive contractions.2 The responses of the jejunum (2.5–40 Hz, 8 s) were unaffected by the μ‐receptor ligands morphine (0.3 μM) and RX 783006 (0.3 μM) or the k‐receptor ligand, ethylketocyclazocine (0.3 μM). The cholinergic contraction of the colon was unaffected by ethylketocycazocine (0.3 μM), but was reduced slightly by morphine at high concentrations only.3 The prototype δ‐opiate receptor ligand D‐Ala2‐D‐Leu5‐enkephalin (DADLE; 30 nM) reduced the contraction during stimulation (2.5, 5, 10 and 20 Hz for 8 s) of the rat jejunum. The IC50 value for inhibition of the contraction elicited by stimulation at 10 Hz was 3.2 in the jejunum and was 12 nM in the ileum. Contractions of the colon were only slightly inhibited at a high concentration of DADLE (1 μM).4 DADLE had no effect on contractions elicited by acetylcholine, at a concentration of up to 3 μM in segments of jejunum. Naloxone (1 μM) abolished the inhibitory effect of DADLE on the cholinergic contraction of the electrically stimulated jejunum. In addition, naloxone caused a large enhancement of control responses to stimulation.5 Only high concentrations of the antidiarrhoeals loperamide and diphenoxylate inhibited the contraction elicited at 10 Hz in the jejunum (IC50, 1.3 and 7.1 μM, respectively) and ileum (loperamide IC50, 0.5 μM). The same concentrations of these drugs also inhibited the effect of exogenously added acetylcholine. A similar pattern of findings was made in the colon.6 The results show marked differences in responses to transmural stimulation and to opiate drugs compared to those previously obtained from guinea‐pig ileum. Furthermore, it appears from the results that the cholinergic nerves of the rat jejunum and ileum possess non‐μ, non‐k, enkephalin‐sensitive opiate receptors, which upon stimulation reduce the amount of depolarization‐induced acetylcholine release. Finally, the opiate antidiarrhoeals appear to act postsynaptically.
Prejunctional effects of cromakalim, nicorandil and pinacidil on noradrenergic transmission in rat isolated mesenteric artery
Authors: Fabiani Maurizio E. , Story David F. 
Published: January 2008

1 The present study investigated the effects of cromakalim, nicorandil and pinacidil on resting and stimulation‐induced (S‐I) effluxes of radioactivity from rat isolated mesenteric artery preparations in which the noradrenergic transmitter stores had been radiolabelled with [3H]‐noradrenaline. The efflux of radioactivity evoked by field stimulation of peri‐arterial sympathetic nerves (pulses at 2 Hz frequency in trains of 60 s duration) was taken as an index of transmitter noradrenaline release.2 Cromakalim (1–100 μm) and nicroandil (1–1000 μm) produced minor effects on resting and S‐I effluxes of radioactivity, but these did not exhibit concentration‐dependency.3 Pinacidil (1–1000 μm) produced concentration‐dependent increases, in both resting and S‐I effluxes of radioactivity. With 1000 μm pinacidil, resting and S‐I effluxes were increased to approximately 348% and 358% of their respective control values.4 The effects of pinacidil on resting and S‐I effluxes were unaltered when the neuronal amine transport system was inhibited by desipramine (1 μm).5 Inhibition of monoamine oxidase with pargyline (100μm) treatment markedly reduced the enhancement of resting efflux by 1000 μm pinacidil but did not alter its effect on S‐I efflux. It is proposed that the enhanced resting efflux produced by pinacidil without pargyline treatment consists of deaminated [3H]‐noradrenaline metabolites formed from [3H]‐noradrenaline displaced from transmitter storage vesicles by pinacidil.6 The enhancement of S‐I efflux by pinacidil does not appear to involve disruption of α2‐adrenoceptor auto‐inhibition of transmitter release since equi‐effective concentrations of phentolamine (1 μm) and pinacidil (1000 μm) produced additive effects on S‐I efflux, whereas increasing the concentration of phentolamine from 1 to 2m produced no further increases in S‐I efflux.7 In conclusion this, study has provided no evidence of a prejunctional inhibitory effect of the potassium channel openers cromakalim, nicorandil and pinacidil on transmitter noradrenaline release. However, the findings with pinacidil suggest that, in high concentrations, pinacidil displaces noradrenaline from transmitter stores, such that deaminated noradrenaline metabolites are released from the nerve terminals. Furthermore, pinacidil enhances S‐I transmitter noradrenaline release, possibly by blocking neuronal potassium channels.
The β‐adrenoceptor selectivity profile of BRL 37344 in the pithed rat
Authors: Oriowo M. A. , Sennitt M. V. , Smith S. A. , Ruffolo R. R. , Cawthorne M. A. 
Published: January 2008

1 Rats were pithed in order to srupt baroreflex pathways. Heart rate was used as a measure of β1‐adrenoceptor activity, blood pressure as a measure of β2‐adrenoceptor activity and oxygen consumption and brown adipose tissue temperature as measures of β3‐adrenoceptor activity.2 The effects of the selective β3‐adrenoceptor agonist BRL 37344 were compared with those of isoprenaline, a non‐selective β ‐adrenoceptor agonist, and denopamine and salbutamol, which are respectively β1 and β2‐adrenoceptor agonists.3 Denopamine was 10‐fold more potent on heart rate than blood pressure, whilst salbutamol was 18‐fold more potent on blood pressure than heart rate. These findings confirm that in this preparation increases in heart rate are predominantly β1‐adrenoceptor‐mediated, whilst blood pressure is β2‐adrenoceptor‐mediated. Further confirmation is provided by the blockade with atenolol, of the chronotropic effect, but not the blood pressure effect, of isoprenaline.4 BRL 37344 was the most potent β ‐adrenoceptor agonist on both oxygen consumption and brown adipose tissue temperature, revealing the β3‐nature of these responses. Dose‐response curves for oxygen consumption and brown adipose tissue temperature were identical, whichever of the β ‐adrenoceptor agonists was used. Both systems may be considered equally effective as indicators of β3‐adrenoceptor agonist activity.
Loss of dopamine D1‐like receptors in the umbilical artery of pre‐eclamptic subjects
Authors: De Almeida José Antonio Ferreira , Cavallotti Carlo , Leite Luis Pereira , Ricci Alberto , Zaccheo Damiano , Amenta Francesco 
Published: January 2008

1 The influence of pre‐eclampsia on the density and pattern of dopamine D1‐like receptors was studied in frozen samples of the placental end of the umbilical artery by using radioligand binding and autoradiographic techniques in combination.2 Analysis was performed on normotensive (n= 10) and pre‐eclamptic subjects (n= 9) undergoing caesarean delivery, using [3H]‐SCH 23390 as a ligand. Pre‐eclamptic patients received a low salt diet and were treated with magnesium sulphate and hydralazine. The possibility that this treatment may cause changes in the density of dopamine D1‐like receptors was evaluated by treating male Wistar rats in the same way and by determining [3H]‐SCH 23390 binding in sections of the kidney which represents an organ containing dopamine D1‐like receptors.3 The density of dopamine D1‐like receptors of the umbilical artery, which are probably vasodilatory, was decreased in pre‐eclamptic compared with normotensive subjects. In contrast, the affinity of the radioligand for dopamine D1‐like receptors was not statistically different between normotensive and pre‐eclamptic subjects. Low salt diet, magnesium sulphate and hydralazine treatment did not affect [3H]‐SCH 23390 binding to sections of rat kidney. This suggests that changes in the density of dopamine D1‐like receptors in pre‐eclamptic patients are a specific phenomenon not dependent upon antihypertensive measures.4 Analysis of the pharmacological profile of [3H]‐SCH 23390 binding to sections of the umbilical artery both in normotensive and pre‐eclamptic subjects indicates the labelling of dopamine D5 receptors.5 These findings collectively suggest that the dopaminergic vasodilatory tone in the umbilical artery is impaired in pre‐eclampsia. The possible significance of these data should be clarified in future studies.
Skimmianine and related furoquinolines function as antagonists of 5‐hydroxytryptamine receptors in animals
Authors: Cheng Juei‐Tang , Chang Tzen Kwan , Chent Ih‐Sheng 
Published: January 2008

1 Skimmianine, kokusaginine and confusameline, three furoquinolines extracted from the leaves of Evodia merrillii(Rutaceae), were investigated to characterize their selective effects on subtypes of 5‐hydroxytryptamine (5‐HT) receptors.2 In the isolated membranes of rat cerebrocortex, using [3H]‐5‐HT and [3H]‐ketanserin as radioligands, skimmianine and the two other furoquinolines displaced radioligand bindings in a concentration‐dependent manner. Lower concentrations were required to affect [3H]‐ketanserin binding than [3H]‐5‐HT binding in the order skimmianine > kokusaginine > confusameline.3 Furoquinolines inhibited 5‐HT‐induced contraction mediated by 5‐HT2 receptors in the presence of methiothepin in rat isolated aorta. Also, the combination of furoquinolines with ketanserin showed an additive antagonism.4 These furoquinolines were inactive on the 5‐carboxamidotryptamine‐induced relaxation of guinea‐pig ileum, a 5‐HT1‐mediated event. However, 5‐HT‐induced contraction via 5‐HT2 receptors was reduced by these furoquinolines in a way similar to that in blood vessels.5 The failure of these compounds to affect the 5‐HT‐induced Bezold–Jarisch‐like reflex in anaesthetized rats, the major .5‐HT3‐mediated action, ruled out an action on 5‐HT3 receptors.6 The results obtained suggest that three furoquinoline alkaloids may act on 5‐HT receptors in animals, more selectively to the 5‐HT2 subtype, in the order of skimmianine > kokusaginine > confusameline.