bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional heterogeneity in the contractile and potentiating effects of neuropeptide Y in rat isolated coronary arteries: modulatory action of the endothelium
Authors: Prieto Dolores , Benedito Sara , Simonsen Ulf , Nyborg Niels C. Berg 
Published: July 2012

Neuropeptide Y (NPY) induced a concentration‐dependent contraction of isolated rings of proximal epicardial (PC) and distal intramural (DC) coronary arteries of the rat, with an EC50 of ca. 1 × 10−7 m. The NPY‐induced contraction at 3 × 10−7 m was significantly smaller in PC than DC arteries: 34% vs. 55% of the 125 mm K+‐induced response, respectively.
NPY (2 × 10−8 m) increased the sensitivity to noradrenaline (NA) and 5‐hydroxytryptamine (5‐HT) more in PC (4.2 and 2.8 fold, respectively) than in DC arteries (2.2 and 1.4 fold, respectively). The maximal contractile response to NA and 5‐HT was increased more in DC (43% and 29%, respectively) than in PC arteries (20% and 12%, respectively).
Removal of the endothelium increased the sensitivity and maximal response to NPY as well as the spontaneous myogenic tone in PC but not in DC arteries. NPY had no relaxing effect on PC and DC arteries submaximally contracted with 10−6 m prostaglandin F2α, suggesting that spontaneous rather than stimulated release of endothelium‐derived relaxing factor (EDRF) depresses the contractile action of NPY in PC arteries.
The results indicate a heterogeneity in the contractile and potentiating action of NPY in rat coronary arteries depending on size or location in the coronary circulation.
Deamination of newly‐formed dopamine in rat renal tissues
Authors: Fernandes M. Helena , Pestana Manuel , Soares‐da‐Silva P. 
Published: July 2012

The present study has examined the formation of dopamine and 3,4‐dihydroxyphenylacetic acid (DOPAC) in slices of the rat renal cortex and the renal medulla loaded with exogenous l‐β‐3,4‐dihydroxyphenylalanine (l‐DOPA). The effects of pargyline and of two selective inhibitors of monoamine oxidase (MAO) types A and B, respectively Ro 41–1049 and Ro 19–6327, on the deamination of newly‐synthesized dopamine in kidney slices incubated with exogenous l‐DOPA were also tested. The assay of l‐DOPA, dopamine, noradrenaline and DOPAC was performed by means of h.p.l.c. with electrochemical detection.
Incubation of renal slices with exogenous l‐DOPA resulted in a concentration‐dependent accumulation of dopamine and DOPAC; the tissue levels of newly‐formed dopamine and DOPAC in slices of the renal medulla were 6–8% of those in cortical slices.
Pargyline (0.1 mm) produced a marked decrease (84% reduction) in the formation of DOPAC in kidney slices loaded with 1.0 mm l‐DOPA; this effect was accompanied by a 17% increase in the accumulation of dopamine. Similar effects were obtained at higher concentrations of pargyline (0.5 and 1.0 mm). At 5.0 and 10.0 mm pargyline, a marked decrease (46 and 76% reduction) in the accumulation of newly‐formed dopamine was observed.
The accumulation of dopamine and DOPAC was found to be time‐dependent in experiments in which tissues were incubated with 5 and 10 μm l‐DOPA for 5, 10, 20 and 30 min. Pargyline (0.1 mm) produced an increase in the accumulation of dopamine at all incubation periods and decreased the formation of DOPAC.
Ro 41–1049 (50, 100 and 250 nm) was found to produce a concentration‐dependent increase of newly‐formed dopamine (16–66% increase) and reduced DOPAC formation (44–89% reduction). Ro 19–6327 (50, 100 and 250 nm), was found not to affect the accumulation of newly‐formed dopamine, but significantly reduced the formation of DOPAC.
It is concluded that deamination of newly‐formed dopamine in kidney slices loaded with l‐DOPA constitutes an important mechanism of amine inactivation. The results presented also suggest that most of the MAO, located inside the compartment where the synthesis of dopamine occurs, is of the A type.
GABAB receptor modulation of the release of substance P from capsaicin‐sensitive neurones in the rat trachea in vitro
Authors: Ray N.J. , Jones A.J. , Keen P. 
Published: July 2012

The role of γ‐aminobutyric acid (GABA) as an inhibitory transmitter in the central nervous system is well documented. Recently, GABAA and GABAB receptors have been identified in the peripheral nervous system, notably on primary afferent neurones (PAN). We have utilised a multi‐superfusion system to investigate the effect of selective GABA receptor agonists and antagonists on the release of substance P (SP) from the rat trachea in vitro.
GABA (1–100 μm) did not affect spontaneous release of SP‐like immunoreactivity (LI) but caused dose‐related inhibition of calcium‐dependent potassium (60 mm)‐stimulated SP‐LI release. The greatest inhibition of 77.7 ± 18.8% was observed at 100 μm.
The inhibitory effect of GABA was mimicked by the GABAB receptor agonist, (±)‐baclofen (1–100 μm), but not the GABAA receptor agonist, 3‐amino‐1‐propane‐sulphonic acid (3‐APS, 1–100 μm). Baclofen (100 μm) had no effect on SP‐LI release stimulated by capsaicin (1 μm).
The inhibitory effect of baclofen (30 μm) was significantly reduced by prior and concomitant exposure to the GABAB receptor antagonist, phacolofen (100 μm) but not the GABAA receptor antagonist, bicuculline (10 μm). Neither antagonist, alone, affected spontaneous or potassium‐stimulated SP‐LI release.
We conclude that activation of pre‐synaptic GABAB receptors on the peripheral termini of PANs in the rat trachea inhibits SP‐LI release and suggest that GABAB receptor agonists may be of value in the therapeutic treatment of asthma.
Comparison of endothelium‐dependent responses of monkey cerebral and temporal arteries
Authors: Toda Noboru , Kawakami Masahisa , Yamazaki Masaaki , Okamura Tomio 
Published: July 2012

Endothelium‐dependency of vasodilator responses was compared in helical strips of monkey cerebral and superficial temporal arteries contracted with prostaglandin F2α. Acetylcholine produced an endothelium‐dependent relaxation in the temporal arteries, but did not consistently alter the tone of cerebral arteries.
Adenosine 5′‐triphosphate (ATP) produced a transient contraction followed by a relaxation in the temporal and cerebral arteries; removal of the endothelium partially attenuated the relaxation of the cerebral arteries and markedly suppressed the relaxation in the temporal arteries. The dependency of adenosine 5′‐diphosphate (ADP)‐induced relaxations on the endothelium was also greater in temporal arteries than in cerebral arteries.
Histamine‐induced relaxations in the temporal arteries were independent of the endothelium and were reversed to contractions by cimetidine. Cerebral arterial relaxations induced by histamine were partly dependent on the endothelium. Relaxations caused by substance P were reversed to contractions by removal of the endothelium in the temporal arteries, whereas the peptide did not consistently alter the tone of cerebral arteries.
The Ca2+ ionophore, A23187, relaxed the temporal and cerebral arteries to a similar extent; removal of the endothelium abolished these relaxations. Glyceryl trinitrate elicited similar relaxations of cerebral and temporal arteries, and these were independent of the endothelium.
These findings clearly indicate heterogeneity in the endothelium‐dependency of several vasodilator responses in monkey intra‐ and extracranial arteries, although the ability of these arteries to respond to A23187 and glyceryl trinitrate does not appear to differ. The heterogeneous responses observed so far could therefore be due to different distributions of receptors or to variation in receptor‐effector coupling in endothelial cells.
Haemodynamic responses to NG‐monomethyl‐l‐arginine in spontaneously hypertensive and normotensive Wistar‐Kyoto rats
Authors: Fozard John R. , Part Marie‐Louise 
Published: July 2012

Nitric oxide (NO) is a major component of endothelium‐derived relaxing factor (EDRF) the synthesis of which from l‐arginine can be inhibited by NG‐monomethyl‐l‐arginine (l‐NMMA). To assess whether basal NO tone is different in experimental hypertension, the haemodynamic effects of l‐NMMA have been compared in anaesthetized spontaneously hypertensive (SH) and normotensive Wistar‐Kyoto (WKY) rats in which autonomic reflexes were blocked by ganglion blockade.
Bolus intravenous injections of l‐NMMA, 1–30 mg kg−1, but not d‐NMMA, 1–30 mg kg−1, induced dose‐related increases in mean arterial pressure and decreases in conductances in the renal, carotid, hindquarters and mesenteric vascular beds in both SH and WKY rats. Although the different vascular beds varied in their maximum responses to l‐NMMA, there were neither qualitative nor quantitative differences between the two rat strains in this respect.
The effects of l‐NMMA, 30 mg kg−1, i.v. on all parameters were rapidly and completely reversed by l‐arginine, 30 mg kg−1, i.v., in both SH and WKY rats.
The results indicate that NO derived from l‐arginine exerts a powerful vasodilator tone in both anaesthetized, ganglion‐blocked SH and WKY rats. Although NO appears to contribute differentially to tone in the different vascular beds, there were no major differences between the two rat strains in this respect. Hence a reduced NO tone to the vasculature is unlikely to be a major factor contributing to the elevated blood pressure in the adult SH rat.
Convulsive thresholds in mice during the recovery phase from anaesthesia induced by propofol, thiopentone, methohexitone and etomidate
Authors: Lowson S. , Gent J.P. , Goodchild C.S. 
Published: July 2012

Convulsive thresholds were measured with intravenous pentylenetetrazol in mice during the recovery phase after intravenous anaesthetic doses of propofol (10 and 20 mg kg−1), thiopentone (30 mg kg−1), methohexitone (10 mg kg−1), and etomidate 3 mg kg−1).
The convulsive threshold rose after each agent, indicating an anticonvulsant action for all the drugs tested; this declined to control values with initial half times of: 1.56 min (propofol 10 mg kg−1); 1.03 min (propofol 20 mg kg−1): 1.02 min (methohexitone); 3.35 min (etomidate); 13.7 min (thiopentone).
At no time during the recovery phase of any agent did the convulsive threshold fall below control values, which might indicate an epileptogenic effect of the drug.
The threshold was depressed below control values by intravenous administration of Ro 15–4513, a partial inverse agonist at the benzodiazepine receptor, thus indicating the ability of this pentylenetetrazol test to demonstrate a proconvulsant effect.
We conclude that the abnormal movements or convulsions associated with recovery from anaesthesia with short‐acting intravenous anaesthetics may not be the result of an intrinsic proconvulsant action of the drugs.
Inability of an opioid antagonist lacking negative intrinsic activity to induce opioid receptor up‐regulation in vivo
Authors: Morris B.J. , Millan M.J. 
Published: July 2012

It has recently been suggested that opioid antagonists may be divided into those possessing negative intrinsic activity (e.g. naloxone) and those with neutral intrinsic activity (e.g. MR2266).
MR2266 was chronically administered to rats by subcutaneous infusion at a dose of 0.3 mg kg−1 h−1 for 1 week.
This dose reduced ingestive behaviour and blocked the antinociceptive effects of a κ‐agonist, indicating occupation of opioid receptors in vivo.
No supersensitivity could be detected to the antinociceptive actions of μ or κ agonists, either one or two days after cessation of treatment.
No up‐regulation of μ, δ or κ binding sites was observed.
Since naloxone induces both supersensitivity and receptor up‐regulation under equivalent conditions, the results suggest that negative intrinsic activity may be required for these phenomena to occur.
Effects of helospectin I on insulin and glucagon secretion in the mouse
Authors: Ahrén Bo 
Published: July 2012

The helospectins are peptides structurally related to helodermin, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI) and secretin, which all potently stimulate glucagon secretion in the mouse. Therefore, the effects of helospectin I (0.1–0.8 nmol kg−1) on insulin and glucagon secretion under basal conditions and after stimulation with glucose (2.8 mmol kg−1) or the cholinoceptor agonist, carbachol (0.16 μmol kg−1), were examined in vivo in the mouse.
Helospectin I potently increased plasma levels of glucagon after its intravenous injection in mice. The increase was observed after only 2 min, and was evident also after 6 min.
In contrast, plasma insulin levels were not altered by helospectin I after 2 min, but slightly increased after 6 min. Plasma glucose levels were not altered by the peptide.
Carbachol‐induced glucagon secretion was markedly potentiated by helospectin I. In contrast, glucose‐ or carbachol‐stimulated insulin secretion was not affected by the peptide.
In conclusion, helospectin I markedly stimulates glucagon secretion in the mouse whereas the peptide has no direct action on insulin secretion. This pattern of effect of helospectin I is similar to that previously reported for helodermin, VIP, PHI and secretin in the mouse, i.e., for all peptides belonging to this superfamily of peptides.
Interactions between the vascular peptide endothelin‐1 and sensory neuropeptides in gastric mucosal injury
Authors: Whittle B.J.R. , Lopez‐Belmonte J. 
Published: July 2012

The interactions between endogenous and exogenous sensory neuropeptides on gastric mucosal injury induced by endothelin‐1 (ET‐1) have been investigated in the anaesthetized rat.
Close intra‐arterial infusion of ET‐1 (4–20 pmol kg−1 min−1) dose‐dependently induced vasocongestion and haemorrhagic necrosis in the gastric mucosa.
Capsaicin‐pretreatment, two weeks earlier to deplete sensory neuropeptides from primary afferent neurones, augmented the mucosal damage induced by ET‐1, as assessed by both macroscopic and histological examination.
The damage induced by threshold doses of ET‐1 alone or in capsaicin‐pretreated rats was further enhanced by administration of indomethacin (5 mg kg−1, i.v.), indicating a modulatory influence of endogenous prostanoids.
Morphine administration (3 mg kg−1, i.v.), which can prevent neuropeptide release, augmented the damage induced by threshold doses of ET‐1, this effect being reversed by naloxone (1 mg kg−1, i.v.).
Concurrent local intra‐arterial infusion of rat α‐calcitonin gene‐related peptide (10–50 pmol kg−1 min−1) dose‐dependently reduced the mucosal injury induced by ET‐1.
These findings suggest interactions between ET‐1 and sensory neuropeptides, which may reflect an important influence of these peptide mediators in the regulation of mucosal integrity.
A selective effect of protein kinase C activators on noradrenaline release compared with subsequent contraction in canine isolated saphenous veins
Authors: Takata Yoshinobu , Ozawa Junko , Kato Hitoshi 
Published: July 2012

Effects of protein kinase C (PKC) activators and inhibitors on both tritium overflow and subsequent contraction evoked by transmural nerve stimulation (TNS) were investigated in canine saphenous veins prelabelled with [3H]‐noradrenaline.
Activation of PKC by stepwise increasing concentrations (0.01 nm–1 μm) of 12‐O‐tetradecanoylphorbol 13‐acetate (TPA), phorbol 12,13‐dibutyrate (PDBu) or mezerein caused a significant and concentration‐dependent enhancement of the tritium overflow evoked by TNS, while the activators failed to affect the corresponding contraction except with the highest concentration of PDBu when the contraction was significantly reduced. Phorbol, which is inactive on PKC, had no effects on the tritium overflow and contraction induced by TNS.
PKC inhibitors, polymyxin B (1 and 10 μm) and the isoquinolinesulphonamide, H‐7 (1 μm), inhibited significantly the phorbol ester‐potentiated tritium overflow evoked by TNS with no effects on the contraction. H‐7 and the related inhibitor H‐8 at 10 μm reduced significantly both responses to TNS in the presence of TPA, while they suppressed only the TNS‐induced contraction in the absence of TPA.
None of the PKC activators or inhibitors affected the spontaneous tritium overflow.
PDBu (0.01 and 0.1 μm) elevated resting tension of the veins more effectively than TPA and mezerein.
These results suggest that PKC may modulate electrically stimulated noradrenaline release from adrenergic nerve endings of the canine saphenous veins and the PKC activators may act more selectively on presynaptic than postsynaptic sites, but have no apparent effect on postjunctional noradrenergic mechanisms.
Bradykinin stimulates production of inositol (1,4,5) trisphosphate in cultured mesangial cells of the rat via a BK2‐kinin receptor
Authors: Bascands J.L. , Emond C. , Pecher C. , Regoli D. , Girolami J.P. 
Published: July 2012

Using [125I‐Tyr0]‐BK, as radiolabelled ligand, and various agonists and antagonists of bradykinin (BK) we identified a single class of specific BK2‐binding sites in mesangial cell membranes (Bmax = 73 fmol mg−1 protein and Kd = 3.7 nm).
Following the addition of 0.1 μm BK, inositol (1,4,5) trisphosphate (IP3) formation increased within 20 s from a basal level of 64 to a maximal value of 175 pmol mg−1 protein.
Incubation in a Ca2+‐free medium did not change IP3 production but a 5 min preincubation with 1 mm EGTA completely prevented the BK‐induced IP3 formation, suggesting that IP3 formation is partly dependent on extracellular calcium.
The BK2 antagonist d‐Arg‐Hyp3‐d‐Phe7‐BK (10 μm) but not the BK1 antagonist (des‐Arg9‐Leu8‐BK) abolished IP3 production in response to 0.1 μm BK. Pretreatment of mesangial cells with pertussis toxin was without effect on BK‐induced IP3 formation, whereas phorbol 12‐myristate 13‐acetate significantly enhanced (by 25%) BK‐induced IP3 formation.
The present data demonstrate that inositol phosphate breakdown in rat mesangial cells can be mediated via activation of a BK2‐kinin receptor and is under negative control of protein‐kinase C.
Blood pressure and vascular reactivity changes in spontaneously hypertensive rats fed fish oil
Authors: Yin K. , Chu Z.M. , Beilin L.J. 
Published: July 2012

To examine possible mechanisms of antihypertensive effects of feeding fish oil rich in n‐3 fatty acids, we have studied vascular reactivity of aortic rings and perfused mesenteric resistance vessels of spontaneously hypertensive rats (SHR) given such a diet.
In two experiments, rats were fed a semi‐synthetic diet containing either ‘fish oil’ (10 and 20% by weight) or hydrogenated coconut oil (control) (10 and 20%) for 4 weeks.
Blood pressure rose significantly less in the fish oil group than in controls in both experiments.
Aortic rings from control rats showed endothelium‐dependent relaxations to low concentrations of acetylcholine (ACh) but relaxed less at higher concentrations. In contrast, rings from the fish oil group had relaxations which increased through the range of concentrations used. Indomethacin (10 μm) also increased the relaxation responses seen in rings from control rats, suggesting that fish oil inhibits a contractile cyclo‐oxygenase product. This contractile substance may be thromboxane A2 (TxA2) or its endoperoxide precursor, prostaglandin H2 (PGH2) as aortic incubates and serum levels of TxB2 (the stable product of TxA2) were greatly reduced in fish oil‐fed rats, and the decrease of relaxant responses to high concentrations of ACh were also blocked by a TxA2/PGH2 receptor blocker (SQ 29548).
In contrast to aortic rings, perfused preconstricted mesenteric resistance vessels of control rats relaxed to ACh in a similar fashion to tissues from fish oil‐fed rats. However, in this preparation, fish oil feeding enhanced relaxations to sodium nitroprusside (SNP) and contractile responses to noradrenaline were less than controls. After removal of endothelium with 0.05% saponin, contractile responses to noradrenaline increased in both groups but responses from fish oil‐treated rats were still attenuated. This suggests that fish oil feeding alters reactivity of mesenteric resistance vessels at the level of the smooth muscle.
The results indicate that fish oil feeding may reduce blood pressure by decreasing vascular smooth muscle reactivity to noradrenaline in resistance vessels. The effect may be enhanced by inhibition of an endothelium‐derived cyclo‐oxygenase product, such as TxA2 or PGH2 in conduit vessels.
Bioassay of nitric oxide released upon stimulation of non‐adrenergic non‐cholinergic nerves in the canine ileocolonic junction
Authors: Boeckxstaens Guy E. , Pelckmans Paul A. , Ruytjens Isabelle F. , Bult Hidde , De Man Joris G. , Herman Arnold G. , Van Maercke Yvan M. 
Published: July 2012

The release and the nature of the inhibitory non‐adrenergic non‐cholinergic (NANC) neurotransmitter was studied in the canine ileocolonic junction. A circular muscle strip of the canine ileocolonic junction served as donor tissue in a superfusion bioassay in which rings of rabbit aorta with the endothelium removed served as detector tissue.
The ileocolonic junction released a labile factor with vasodilator activity upon stimulation of non‐adrenergic non‐cholinergic (NANC) nerves in response to electrical impulses and the nicotinic receptor agonist 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP). This release was respectively frequency‐ and concentration‐dependent.
The release was reduced by the blocker of neuronal conductance, tetrodotoxin, and by the inhibitor of the nitric oxide (NO) biosynthesis NG‐nitro‐l‐arginine. The biological activity was enhanced by superoxide dismutase and eliminated by haemoglobin. Hexamethonium abolished only the release in response to DMPP.
Injection of adenosine 5′‐triphosphate (ATP) or vasoactive intestinal polypeptide (VIP) onto the cascade induced relaxations of the rabbit aorta but they were different from those induced by NO or the transferable factor.
Based on organ bath experiments in which the reactivity of different parts of the circular smooth muscle layer of the ileocolonic junction was investigated, a muscle strip of superficial circular muscle with submucosa was chosen as the detector strip in the bioassay cascade.
The ileocolonic junction dose‐dependently relaxed in response to nitroglycerin and NO. NO was much more potent in the rabbit aorta than in the canine ileocolonic junction. Equivalent amounts of the transferable factor, endothelium‐derived relaxing factor and NO, as assessed by the relaxation of the rabbit aorta, failed to affect the ileocolonic junction.
In conclusion, our results demonstrate the release of a transferable vasorelaxant factor in response to NANC nerve stimulation which behaves pharmacologically like NO but not like ATP or VIP. Therefore, we suggest that NO or a NO releasing substance is the inhibitory NANC neurotransmitter in the canine ileocolonic junction.
Adenosine‐induced dilatation of the rabbit hepatic arterial bed is mediated by A2‐purinoceptors
Authors: Mathie R.T. , Alexander B. , Ralevic V. , Burnstock G. 
Published: July 2012

This study was carried out in order to identify the receptor responsible for adenosine‐induced dilatation of the hepatic arterial vascular bed.
Livers of 10 New Zealand White rabbits were perfused in vitro with Krebs‐Bülbring buffer via the hepatic artery and the portal vein at constant flows of 26 and 77 ml min−1 100 g−1 liver respectively. The tone of the preparation was raised by the presence of noradrenaline in the perfusate (concentration: 10−5 m).
Dose‐response curves for adenosine and its analogues 5′‐N‐ethyl‐carboxamido‐adenosine (NECA), the 2‐substituted NECA analogue CGS 21680C, and R‐ and S‐N6‐phenyl‐isopropyl‐adenosine (R‐ and S‐PIA) were obtained after their injection into the hepatic arterial supply.
The order of vasodilator potency of these agents was: NECA > CGS 21680C > adenosine > R‐PIA > S‐PIA. Their potency, expressed relative to that of adenosine, was in the approximate ratio 10:3:1:0.3:0.1, consistent with that resulting from activation of P1‐purinoceptors of the A2 sub‐type (which mediate vasodilatation due to adenosine).
The P1‐purinoceptor antagonist 8‐phenyltheophylline (10−5 m) caused significant attenuation of the vasodilatation to adenosine and analogues.
It is concluded that adenosine‐induced dilatation of the hepatic arterial vascular bed is mediated by P1‐purinoceptors of the A2 sub‐type.