bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased secretion of glandular‐kallikrein in the bronchial washings induced by intravenous injection of leukotriene C4 in guinea‐pigs
Authors: Jin Hong Yong , Katori Makoto , Majima Masataka , Sunahara Noriyuki 
Published: July 2012

Intravenous administration of leukotriene C4 (LTC4) and LTD4 (1–10 nmol kg−1) caused a dose‐dependent increase in secretion of glandular‐kallikrein in the bronchial washings of guinea‐pigs, as measured by cleavage of a synthetic substrate and the formation of kinin. LTC4 was more potent than LTD4 and pilocarpine was much less potent than peptide leukotrienes on a molecular basis.
The increases in levels of glandular‐kallikrein in the bronchial washings that were induced by LTC4 (3 nmol kg−1, i.v.) were almost completely inhibited by pretreatment with an antagonist of leukotrienes (ONO‐1078), with an antagonist of thromboxane (S‐1452), with an inhibitor of thromboxane synthetase (OKY‐046), with indomethacin, with atropine or with scopolamine. These results indicate that the LTC4‐induced increase in levels of glandular‐kallikrein may have been mediated by the formation of thromboxane and the release of acetylcholine.
The increases in levels of glandular‐kallikrein in the bronchial washings induced by STA2 (20 pmol kg−1, i.v.), a stable analogue of thromboxane A2, were completely blocked by pretreatment with atropine, whereas increases induced by pilocarpine (41 μmol kg−1, i.v.) were not blocked by pretreatment with indomethacin, although such increases were inhibited by atropine. This result indicates that secretion of kallikrein stimulated by LTC4 may have been mediated by the successive formation of thromboxane A2 and release of acetylcholine.
Intravenous administration of bradykinin (3–30 nmol kg−1) caused a dose‐dependent increase in levels of glandular‐kallikrein in the bronchial washings. This increase was completely inhibited by pretreatment with atropine, with indomethacin or with an antagonist of thromboxane.
The increases in levels of glandular‐kallikrein in the bronchial washings induced by LTC4 (3 nmol kg−1, i.v.) and pilocarpine (41 μmol kg−1, i.v.) were significantly inhibited by pretreatment with an antagonist of bradykinin. These results suggest that intravenous LTC4 may increase secretion of glandular‐kallikrein via formation of thromboxane A2 and release of acetylcholine in that order, and kinin released by kallikrein may enhance the rate of secretion of glandular‐kallikrein.
Sustained decreases in weight and serum insulin, glucose, triacylglycerol and cholesterol in JCR: LA‐corpulent rats treated with d‐fenfluramine
Authors: Brindley David N. , Hales Paul , Al‐Sieni Abdulbasit I.I. , Russell James C. 
Published: July 2012

The effects of d‐fenfluramine were studied in the JCR: LA‐corpulent rat that is grossly obese, hyperphagic, hyperlipidaemic, hyperinsulinaemic and atherosclerosis‐prone.
Daily doses of 1, 2.5 and 5 mg kg−1 of d‐fenfluramine produced sustained decreases in body weight and food intake over a period of 30 days in 6 month old female rats fed ad libitum. This was accompanied by decreases in the circulating concentrations of glucose, triacylglycerol, free cholesterol and insulin.
Food restriction imposed by meal feeding also decreased circulating glucose, triacylglycerols, cholesterol and insulin and diminished the effect of d‐fenfluramine on these parameters in male and female rats.
Addition of d‐fenfluramine to drinking water to give a dose of about 0.25 mg kg−1 daily produced a sustained decrease in body weight and food intake of male and female rats over a nine week period.
The results show that the JCR: LA‐corpulent rat is very sensitive to the pharmacological effects of d‐fenfluramine. These rats should provide an appropriate animal model for determining the mechanisms of action of this antiobesity agent and whether apparently beneficial changes in metabolism translate into long‐term protection against premature atherosclerosis.
Release of vasoactive intestinal polypeptide from the rat gastric fundus
Authors: D'Amato M. , Currò D. , Montuschi P. , Ciabattoni G. , Ragazzoni E. , Lefebvre R.A. 
Published: July 2012

Auxotonic responses and release of vasoactive intestinal polypeptide‐like immunoreactivity (VIP‐LI) induced by electrical field stimulation (EFS) were studied in longitudinal muscle strips from the gastric fundus of reserpinized rats suspended between parallel platinum electrodes in Krebs solution containing atropine (1 μm), 5‐hydroxytryptamine (3 μm) and bovine serum albumin (50 mg l−1).
EFS (supramaximal voltage, 1 ms, 0.25–32.0 Hz, trains of 2 min) induced frequency‐dependent relaxations.
EFS at frequencies ≥ 8 Hz also produced significant increases in VIP‐LI release.
VIP‐LI release induced by EFS at 16 Hz no longer occurred in the presence of tetrodotoxin (1 μm) or a Ca2+‐free medium.
Detection of VIP‐LI upon activation of inhibitory non‐adrenergic, non‐cholinergic neurones indicates that VIP meets the ‘detectable release’ criterion for an inhibitory neurotransmitter in the rat gastric fundus.
Participation of endothelium‐derived nitric oxide but not prostacyclin in the gastric mucosal hyperaemia due to acid back‐diffusion
Authors: Lippe Irmgard Th. , Holzer Peter 
Published: July 2012

The possible participation of prostacyclin and nitric oxide (NO) in the gastric mucosal hyperaemic response to acid back‐diffusion through a disrupted gastric mucosal barrier was examined. The experiments were carried out on anaesthetized rats in which acid back‐diffusion was elicited by gastric perfusion with dilute ethanol in 0.15 m HCl and gastric mucosal blood flow (MBF) was measured by the hydrogen gas clearance technique.
Indomethacin (28 μmol kg−1, s.c.), an inhibitor of the formation of cyclo‐oxygenase products including prostacyclin, failed to alter mean arterial blood pressure (MAP), basal MBF and the hyperaemic response to acid back‐diffusion in urethane‐anaesthetized rats.
NG‐nitro‐l‐arginine methyl ester (l‐NAME; 13 and 43 μmol kg−1, i.v.), an inhibitor of endothelium‐derived NO formation, increased MAP in a dose‐dependent manner. Whilst basal MBF in urethane‐anaesthetized rats was not changed, the increase in MBF caused by gastric perfusion with dilute ethanol in acid was dose‐dependently depressed by l‐NAME. The loss of H+ ions from the gastric lumen, an indirect measure of acid back‐diffusion, was significantly enhanced by 43 μmol kg−1 l‐NAME. In contrast, d‐NAME (13 and 43 μmol kg−1) was without effect on MAP, basal and stimulated MBF, and acid back‐diffusion.
Unlike in urethane‐anaesthetized rats, l‐NAME led to a significant reduction of basal MBF in phenobarbitone‐anaesthetized rats. MAP in the phenobarbitone‐anaesthetized rats was significantly higher than in urethane‐anaesthetized rats, and the hypertensive effect of l‐NAME under phenobarbitone anaesthesia was significantly smaller than under urethane anaesthesia.
The rise in MBF brought about by acid back‐diffusion was blocked by l‐NAME administered to phenobarbitone‐anaesthetized rats. Infusion of l‐arginine (120 μmol kg−1 min−1, i.v.) led to a partial, but significant, reversal of the effects of l‐NAME on MAP and the hyperaemia due to acid back‐diffusion.
These findings indicate that endothelium‐derived NO plays an important mediator role in the gastric mucosal vasodilatation caused by back‐diffusion whilst vasodilator prostanoids such as prostacyclin are not involved.
Differential cardiovascular and neuroendocrine effects of epinine and dopamine in conscious pigs before and after adrenoceptor blockade
Authors: van Woerkens L.J. , Boomsma F. , in 't Veld A.J. Man , Bevers M.M. , Verdouw P.D. 
Published: July 2012

The effects of epinine or dopamine (both 1–10 μg kg−1 min−1) on systemic haemodynamics and plasma concentrations of catecholamines and prolactin were studied in conscious pigs before and after combined non‐selective α‐ and β‐adrenoceptor blockade.
The plasma concentrations of the two compounds did not differ from each other over the entire dose‐range.
Epinine increased aortic blood flow (AoBF, 24 ± 6%), which was due to an increase in heart rate (HR) for doses less than 10 μg kg−1 min−1. At 10 μg kg−1 min−1, HR decreased slightly (10 ± 3%, as compared to the value obtained at 5 μg kg−1 min−1) and stroke volume increased up to 15% (P < 0.05). Mean arterial pressure (MAP, 99 ± 3 mmHg at baseline) decreased dose‐dependently (14 ± 2%, P < 0.05) up to the infusion rate of 5 μg kg−1 min−1, but increased by 4.0 ± 1.8 mmHg during infusion of 10 μg kg−1 min−1. Systemic vascular resistance (SVR) decreased up to 23 ± 3% for doses less than 10 μg kg−1 min−1, but did not change further during infusion of the highest dose. LVdP/dtmax increased during the two highest infusion rates up to 22 ± 6% (P < 0.05). After the infusion was stopped there was an abrupt increase in HR (18 ± 4%, P < 0.05) and a further decrease in SVR before all parameters returned to baseline.
Dopamine caused increases in AoBF (27 ± 3%) similar to epinine, the only difference being that HR continued to increase (32 ± 5%) and MAP (13 ± 3%) and SVR continued to decrease (31 ± 3%) over the entire dose‐range. The increase in LVdP/dtmax at the highest dose (48 ± 4%, P < 0.05) was more pronounced than with epinine.
Adrenoceptor blockade inhibited all epinine‐induced changes, but did not affect the dopamine‐induced changes in AoBF, SVR and MAP, but attenuated the increases in HR and LVdP/dtmax.6 Noradrenaline (NA) and adrenaline (Ad) concentrations did not change during infusion of epinine or dopamine, but NA increased by 50% within 2.5 min after stopping the infusion of epinine. After adrenoceptor blockade NA and Ad concentrations did not change during infusion of dopamine, which contrasted with a decrease of 55 ± 5% (P < 0.05) in NA during infusion of epinine.7 Prolactin concentrations decreased gradually from 480 ± 40 pg ml−1 to 270 ± 50 pg ml−1 (P < 0.05) during infusion of epinine, but did not change significantly during dopamine infusion.8 The differential effects of epinine and dopamine on MAP, SVR, plasma NA (before and after adrenoceptor blockade) and prolactin, leads us to conclude that in conscious pigs, epinine is a more potent α, β2 and D2‐receptor agonist, but a weaker D1‐receptor agonist than dopamine.
Inhibition of sympathetic hypertensive responses in the guinea‐pig by prejunctional histamine H3‐receptors
Authors: Hey J.A. , del Prado M. , Egan R.W. , Kreutner W. , Chapman R.W. 
Published: July 2012

The effect of (R)‐α‐methylhistamine, a selective H3‐histamine receptor agonist, was examined on the neurogenic hypertension and tachycardia that is induced by stimulation of areas in the medulla oblongata of guinea‐pigs. Electrical medullary stimulation (32 Hz, 3–5 s trains, 0.5–1.0 ms square pulse, 25–400 μA) produced intensity‐dependent increases in blood pressure and a more variable tachycardia.
(R)‐α‐methylhistamine inhibited the hypertension and tachycardia due to submaximal CNS stimulation. The inhibition of hypertension by (R)‐α‐methylhistamine was dose‐dependent (10–300 μg kg−1, i.v.) and was not seen at high intensities of stimulation.
(R)‐α‐methylhistamine (300 μg kg−1, i.v.) did not attenuate the pressor response to adrenaline (1 and 3 μg kg−1, i.v.), indicating that the effect of (R)‐α‐methylhistamine was not mediated by a postjunctional action on smooth muscle.
The inhibition of CNS‐induced hypertension by (R)‐α‐methylhistamine (300 μg kg−1, i.v.) was blocked by the H3 antagonists, thioperamide (ID50 = 0.39 mg kg−1, i.v.), impromidine (ID50 = 0.22 mg kg−1, i.v.) and burimamide (ID50 = 6 mg kg−1, i.v.). The rank order potency of these antagonists is consistent with activity at the H3B receptor subtype. Chlorpheniramine (30 μg kg−1, i.v.) and cimetidine (3 mg kg−1, i.v.) did not antagonize the inhibition of CNS‐hypertension by (R)‐α‐methylhistamine.
These results suggest that (R)‐α‐methylhistamine inhibits sympathetic hypertensive responses in guinea‐pigs by activation of prejunctional H3‐receptors, possibly located on postganglionic nerve terminals. Furthermore, on the basis of the rank order potency to different H3‐antagonists, it appears that the H3B‐receptor subtype is involved with H3‐receptor responses on vascular sympathetic nerves.
Evidence for a noradrenergic innervation to α1A‐adrenoceptors in rat kidney
Authors: Blue David R. , Vimont Rachel L. , Clarke David E. 
Published: July 2012

Experiments were undertaken to characterize the α1‐adrenoceptor subtype mediating vasoconstrictor responses to periarterial noradrenergic nerve stimulation (PNS) in the isolated perfused kidney of the rat.
Vasoconstrictor responses to nerve stimulation were inhibited by prazosin (10 nm), 5‐methyl‐urapidil (30 nm), and nitrendipine (1 μm) but were resistant to inhibition by chloroethylclonidine (100 μm).
5‐Methyl‐urapidil (30 nm), chloroethylclonidine (100 μm) and nitrendipine (1 μm) did not inhibit the neuronal release of tritium from nerves loaded with [3H]‐noradrenaline.
The results suggest that renovascular α1A‐adrenoceptors receive a noradrenergic innervation and that the innervated receptors are coupled to dihydropyridine‐sensitive calcium channels.
Bradykinin B2 receptor‐mediated phosphoinositide hydrolysis in bovine cultured tracheal smooth muscle cells
Authors: Marsh Katrina A. , Hill Stephen J. 
Published: July 2012

Bovine tracheal smooth muscle cells were established in culture to study agonist‐induced phosphoinositide (PI) hydrolysis in this tissue.
Bradykinin (0.1 nm‐10 μm) evoked a concentration‐dependent increase (log EC50 (m) = −9.4 ±0.2; n = 8) in the accumulation of total [3H]‐inositol phosphates in cultured tracheal smooth muscle cells whereas the selective B1 receptor agonist des‐Arg9‐bradykinin (10 μm) was significantly less effective (16% of bradykinin maximal response; relative potency = 0.2 with respect to bradykinin = 100).
The bradykinin‐induced increase in PI hydrolysis was unaffected by the B1 receptor antagonist des‐Arg9[Leu8]‐bradykinin (1 nm‐1 μm) but showed marked attenuation in the presence of the B2 receptor antagonists d‐Arg,[Hyp3,d‐Phe7]‐bradykinin (10 nm‐10 μm) or d‐Arg[Hyp3,Thi5,8,d‐Phe7]‐bradykinin (10 nm‐10 μm). The estimated KB values obtained for these two compounds, assuming competitive antagonism, were 40 ± 14 nm and 8.6 ± 2.8 nm for d‐Arg,[Hyp3,d‐Phe7]‐bradykinin and d‐Arg[Hyp3,Thi5,8,d‐Phe7]‐bradykinin respectively.
We conclude that bradykinin B2 receptors are expressed in cultured bovine tracheal smooth muscle cells and are coupled to PI hydrolysis mechanisms.
Involvement of multiple receptors in the biological effects of calcitonin gene‐related peptide and amylin in rat and guinea‐pig preparations
Authors: Giuliani Sandro , Wimalawansa Sunil J. , Maggi Carlo Alberto 
Published: July 2012

The activity of rat α and β calcitonin gene‐related peptide (CGRP) as compared to the structurally related peptide, rat amylin, has been investigated in the guinea‐pig isolated left atrium (electrically driven), in mucosa‐free strips from the base of the guinea‐pig urinary bladder and in the rat isolated vas deferens (pars prostatica). The antagonist activity of the C‐terminal fragment of human αCGRP, αCGRP(8–37), was also investigated.
In the guinea‐pig isolated left atrium the three peptides produced a concentration‐related positive inotropic effect, amylin being about 16 and 31 times less potent than α or βCGRP, respectively. Human αCGRP(8–37) produced a rightward displacement of the log concentration‐response curve to the three agonists tested, without depression of maximal response attainable. Apparent pKB values calculated on the basis of the displacement produced by 1 μm human αCGRP(8–37) indicated an agonist‐independent affinity of the antagonist (6.66 ± 0.11 for αCGRP, 6.42 ± 0.17 for βCGRP and 6.95 ± 0.11 for amylin).
In the guinea‐pig isolated urinary bladder, α or βCGRP or amylin produced a concentration‐related inhibition of twitch contractions evoked by train electrical field stimulation (10 Hz frequency, 0.25 ms duration at 100 V for 0.5 s every 60 s). Amylin was about 100 times less potent than α or βCGRP. Human αCGRP(8–37) (3 μm) did not significantly affect the inhibitory action of the three agonists tested.
In the rat isolated vas deferens, α or βCGRP or amylin produced a concentration‐related inhibition of twitch contractions evoked by electrical field stimulation (0.2 Hz frequency, 0.5 ms duration at 60 volts). Amylin was about 100 times less potent than α or βCGRP. Human αCGRP(8–37) at 3 μm did not significantly affect the inhibitory action of amylin and at 3 μm antagonized the responses to rat α and βCGRP with apparent pKB values of 5.86 ± 0.15 and 6.11 ± 0.13, respectively.
These findings indicate that multiple receptors mediate the actions of peptides of the CGRP/amylin family in the preparations investigated. In the guinea‐pig atrium both α and β forms of rat CGRP as well as amylin act by stimulating a single class of receptors which are sensitive to the inhibitory action of human αCGRP(8–37). In rat isolated vas deferens, at least two receptors could be present, one activated by α and βCGRP and partially sensitive to human αCGRP(8–37) and another which is sensitive to amylin but not recognised by human αCGRP(8–37). This latter type of receptor could be entirely responsible for the action of the agonists in the guinea‐pig urinary bladder.
Electrophysiological effects of CRE‐1087 in guinea‐pig ventricular muscles
Authors: Delpón Eva , Valenzuela Carmen , Pérez Onésima , Tamargo Juan 
Published: July 2012

The electrophysiological effects of CRE‐1087, a new antiarrhythmic drug, were studied in guinea‐pig papillary muscles.
CRE‐1087 (10−7 m‐10−4 m) produced a concentration‐dependent decrease in the action potential amplitude and Vmax of the upstroke without altering the action potential duration or the resting membrane potential.
At 5 × 10−6 m, CRE‐1087 produced a 5.0 ± 1.0% tonic Vmax block and this value was not modified at the different rates of stimulation tested. In the presence of CRE‐1087, trains of stimuli at rates between 0.5 and 3 Hz led to an exponential decline in Vmax (frequency‐dependent Vmax block) which augmented at higher rates of stimulation. At 2 Hz the onset kinetics of the frequency‐dependent Vmax block was fitted by a monoexponential function being the K value 0.099 ± 0.012 AP−1. The time constant for the recovery of Vmax from the frequency‐dependent block was prolonged to 18.3 ± 1.5 s.
CRE‐1087 (5 × 10−6 m) did not shift the membrane responsiveness curve.
CRE‐1087 had no effect on the characteristics of the slow action potentials elicited by isoprenaline in ventricular fibres depolarized by 27 mm KCl, which suggested that CRE‐1087 did not exhibit class IV (Ca antagonist) antiarrhythmic actions.6 The slow onset and the slow offset kinetics of frequency‐dependent Vmax block during repetitive activity suggested that in guinea‐pig ventricular muscle fibres CRE‐1087 exhibited class Ic antiarrhythmic actions.
Possible mechanisms of inhibition with atropine against noradrenaline‐induced contraction in the rabbit aorta
Authors: Satake Nobuhiro , Kiyoto Sumio , Shibata Shoji , Gandhi Vijayalakshmi , Jones David J. , Morikawa Masako 
Published: July 2012

In the rabbit isolated aorta, atropine (3 × 10−6 m‐10−4 m) inhibited contractile response to noradrenaline without affecting contraction to KCl.
In the presence of contraction to noradrenaline, atropine (3 × 10−7 m‐10−4 m) caused concentration‐dependent relaxation. Pretreatment with theophylline (10−3 m) potentiated the relaxant action of atropine. Relaxation to atropine was not affected by the specific guanosine 3′:5′‐cyclic monophosphate phosphodiesterase inhibitor, M & B 22,948 (10‐4 m), tetraethylammonium (10 mm), indomethacin (10−5 m), propranolol (10−7 m), nifedipine (10−6 m) or removal of the endothelium.
Relaxation to either atropine or prazosin was not affected by preincubation with prazosin and atropine, respectively.
In Ca2+‐free medium containing EGTA and nifedipine, atropine (10−7 m‐10−4 m) inhibited the residual noradrenaline response more than the subsequent Ca2+‐induced contraction. Pretreatment with either theophylline (10−3 m), forskolin (3 × 10−7 m) or a low concentration of prazosin (3 × 10−9 m) also inhibited the residual contraction to noradrenaline and Ca2+. The effect of combined treatment of atropine and any of these agents was much greater than with each individual agent.
Atropine (10−6 m‐10−4 m) also inhibited increases in the level of inositol monophosphates (IP) in response to noradrenaline. Theophylline (10−3 m) and a low concentration of prazosin (3 × 10−9 m) also inhibited IP formation. Combined with atropine, the effect was much greater than with each of these agents individually.6 Atropine did not affect adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) levels in the aorta and also failed to displace specific [3H]‐prazosin binding.7 These results suggest the possibility that smooth muscle relaxation to atropine may be due to the inhibition of phosphoinositide metabolism. The relaxation is not apparently due to an action of atropine on α1‐adrenoceptors, or a change in the level of cyclic AMP.
Thimerosal blocks stimulated but not basal release of endothelium‐derived relaxing factor (EDRF) in dog isolated coronary artery
Authors: Crack Peter , Cocks Thomas 
Published: July 2012

The effect of an acetly‐coA lysolecithin acyltransferase inhibitor, thimerosal, on the release of endothelium‐derived relaxing factor (EDRF) was examined in the greyhound isolated coronary artery.
Thimerosal (1–10 μm) relaxed fully, ring segments of coronary artery which were contracted with the thromboxane A2‐mimetic, U46619 (30 nm). The response was endothelium‐dependent, slow in both onset and time to reach maximum. The maximum relaxation to the highest concentration of thimerosal (10 μm) was maintained for 10–20 min before the tissue slowly regained active force (1–2 h) to the same or higher level as that prior to the addition of thimerosal. At this time the endothelium‐dependent relaxation responses to acetylcholine (ACh), substance P (SP), bradykinin (BK) and the calcium ionophores, ionomycin and A23187 were abolished. The endothelium‐dependent contractions to the nitric oxide synthase inhibitors, NG‐nitro‐l‐arginine (l‐NNA; 10–100 μm) and NG‐monomethyl‐l‐arginine (l‐NMMA: 10–100 μm), however, were unaffected.
Thimerosal (10 μm) did not affect the relaxation curve to sodium nitroprusside (SNP) nor the contraction curve to the thromboxane A2‐mimetic, U46619.
Both the relaxation response to thimerosal and the selective block of the relaxation responses to stimulated EDRF release were unaffected by either indomethacin (10 μm) or superoxide dismutase (150 u ml−1).
l‐NNA (100 μm) significantly blocked the relaxation curves to thimerosal and A23187 but not that to SNP.6 Abolition of stimulated EDRF‐mediated responses with thimerosal was unlikely to result from maximal and maintained stimulation of EDRF release even when active U46619‐induced force had returned to pre‐thimerosal levels, since the relaxation curves to glyceryl trinitrate (GTN) and SNP were markedly attenuated in the presence of SNP and GTN respectively when active force was restored with endothelin‐1 (ET‐1).7 Melittin (1 μm), ionomycin (1 μm) and A23187 (1 μm) each had selective effects on stimulated but not basal EDRF responses, similar to those of thimerosal.8 We propose that stimulated but not ‘basal’ release of EDRF is dependent on the release of arachidonic acid or one of its non‐cyclo‐oxygenase metabolites, possibly by Ca2+‐dependent activation of phospholipase A2.