bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactions of nitric oxide synthase inhibitors and dexamethasone with α‐adrenoceptor‐mediated responses in rat aorta
Authors: Adeagbo Ayotunde S.O. , Triggle Christopher R. 
Published: July 2012

The effects of NG‐nitro‐l‐arginine methyl ester (l‐NAME) and NG‐monomethyl‐l‐arginine (l‐NMMA), their d‐isomers, and dexamethasone on noradrenaline (NA)‐induced contractions and antagonism by α‐adrenoceptor antagonists, have been investigated in rat isolated thoracic aortic rings with/without endothelium.
NA produced concentration‐dependent contractions of isolated aortic rings with EC50 values of 2.41 ± 0.54 (n = 21) and 28.00 ± 8.50 (n = 25) nm for endothelium‐denuded and ‐intact preparations respectively. Acetylcholine (ACh) relaxed NA‐precontracted rings with intact, but not those denuded of endothelium.
Treatment with l‐NAME (1–30 μm), or l‐NMMA (10–500 μm), but not their d‐isomers, resulted in an endothelium‐dependent enhancement of NA‐induced contractions. Pre‐treatment, in vitro, with 0.5 μm dexamethasone neither directly potentiated, nor influenced l‐NAME‐induced potentiation of NA‐mediated contractions in endothelium‐intact rings; however, dexamethasone pretreatment reduced EC50 values for NA, and also prevented l‐NAME‐induced potentiation, in denuded rings equilibrated for 5 h under resting tension.
In both intact and denuded rings, phentolamine, prazosin and WB 4101 shifted NA concentration‐response curves to the right; l‐NAME, and also l‐NMMA, but not their d‐isomers, reversed the blockade as indicated by significant decreases in NA dose‐ratios. In denuded rings, reversal by l‐NAME or l‐NMMA was prevented following pretreatment with dexamethasone.
Following treatment with 5 or 50 nm phenoxybenzamine (PBZ), NA concentration‐response (C‐R) curves were shifted to the right with marked depression of maximal responses; 100 μm l‐NAME reversed the antagonism in both endothelium intact and denuded rings. However, 500 nm PBZ treatment resulted in complete abolition of the responses to NA, and contractions were not restored by either l‐NAME or l‐NMMA.
5‐Hydroxytryptamine (5‐HT)‐induced contractions of aortic rings were potentiated by endothelium denudation and also by l‐, but not d‐, NAME. 5‐HT‐induced contractions were non‐competitively antagonized by 10 nm ritanserin, and 100 μm l‐NAME partially reversed the antagonism in intact but not denuded rings.
It is concluded that the inhibition of constitutive endothelial NO synthase and inducible smooth muscle NO synthase accounts for the ability of l‐NAME, and l‐NMMA, to potentiate the effects of agonists and reduce α‐adrenoceptor antagonism in endothelium‐intact and denuded rings. Furthermore, endothelial cell removal/damage triggers the induction of a smooth muscle NO synthase.
Comparison between carvedilol and captopril in rats with partial ablation‐induced chronic renal failure
Authors: Brooks David P. , Short Brian G. , Cyronak Matthew J. , Contino Lisa C. , DiCristo Martin , Wang Yi‐Xin , Ruffolo Robert R. 
Published: July 2012

The effect of the novel β‐adrenoceptor antagonist and vasodilator, carvedilol (SK&F 105517, ∼ 70 mg kg−1 daily in the food), and captopril (∼ 38 mg kg−1 daily in the drinking fluid) on the progression of chronic renal failure in rats was studied.
Six weeks following partial renal ablation, the urinary protein excretion of the carvediol‐ (60 ± 21 mg day−1) and captopril‐treated (35 ± 9mgday−1) animals was less than 50% that of control rats (133 ± 27 mg d−1).
Serum creatinine (Scr) and urea nitrogen (SUN) concentrations of the carvedilol‐(Scr, 0.63 ± 0.09 mg dl−1; SUN, 11.3 ± 1.2 mg dl−1) and captopril‐treated (Scr, 0.82 ± 0.05 mg dl−1; SUN, 14.1 ± 1.5 mg dl−1) animals were also significantly (P < 0.05) lower than that observed in control animals (Scr, 1.4 ± 0.3 mg dl−1; SUN, 19.2 ± 3.9 mg dl−1), indicating that glomerular filtration rate was improved by both drugs. Plasma renin activity was significantly (P < 0.05) higher in captopril‐treated rats (24.7 ± 4.6 ng angiotensin I ml−1 h−1) than in either carvedilol‐treated (7.9 ± 1.4 ng angiotensin I ml−1 h−1) or control animals (7.4 ± 1.0 ng angiotensin I ml−1 h−1).
Histological examination of the kidneys demonstrated a significantly reduced glomerular hypertrophy and glomerulosclerosis in those animals receiving carvedilol or captopril compared to controls.
Serum carvedilol concentration measured every 6 h for 24 h was variable and ranged on average from 57 ± 13 ng ml−1 at 16 h 00 min to 121 ± 31 ng ml−1 at 03 h 00 min. These data indicate that the rats probably had 24 h systemic exposure to carvedilol.
The present study indicates that carvedilol is effective in attenuating the progression of chronic renal failure in rats.
Role of neuronal and vascular Ca2+‐channels in the ACTH‐induced reversal of haemorrhagic shock
Authors: Guarini Salvatore , Bazzani Carla , Bertolini Alfio 
Published: July 2012

In a rat model of volume‐controlled haemorrhagic shock causing the death of all control (saline‐treated) animals within 30 min, the intravenous (i.v.) bolus injection of ACTH‐(1–24) at a dose of 160 μg kg−1 produced an impressive and sustained restoration of arterial pressure, pulse pressure and respiratory function, with 100% survival at the end of the observation period (2 h).
Both intracerebroventricular (i.c.v., 0.015–0.06 μg kg−1) and i.v. (5 μg kg−1) pretreatment with the N‐calcium channel blocker, ω‐conotoxin GVIA, and i.v. (but not i.c.v.) pretreatment with the L‐calcium channel blocker, nicardipine (125–500 μg kg−1) dose‐dependently prevented the ACTH‐induced shock reversal.
These results further indicate that the effect of ACTH in haemorrhagic shock may involve a neuronal link and the eventual restoration of vascular tone mediated by N‐ and L‐type calcium channels, respectively.
Effect of delayed weaning on opioid receptor control of swim stress‐induced antinociception in the developing rat
Authors: Muhammad Bala Y. , Kitchen Ian 
Published: July 2012

The opioid type of swim‐stress induced antinociception (SIA) is mediated via μ‐sites in preweanling rats and predominantly by δ‐sites in postweanling animals. We have studied the effect of delay of weaning on the receptor transition of this behaviour in the developing rat.
Litters were weaned normally at day 21 or allowed to remain with their mothers until assessment of swim SIA. Animals were stressed by warm water (20°C) swimming for 3 min periods and antinociception assessed by the tail immersion test (50°C).
Naloxone (10 mg kg−1) partially reversed swim SIA in both 25 day old weaned and non‐weaned rats.
Naltrindole (1 mg kg−1) partially reversed swim SIA in 25 day old weaned rats but had no effect in non‐weaned animals. Naltrindole (5 mg kg−1) completely abolished swim SIA in weaned rats but was without effect in non‐weaned groups. Antinociceptive responses to the μ‐agonist, alfentanil (60 μg kg−1) were unaffected by naltrindole at 1 mg kg−1 but were partially reversed at 5 mg kg−1.
In 30 day old non‐weaned rats, naltrindole (5 mg kg−1) abolished the swim SIA.
In conclusion, transition from μ‐ to δ‐receptor control of swim SIA in rat pups can be delayed by between 5 and 10 days by delay of weaning. The environmental stimulus of weaning can activate opioid receptor subtype operation of biological responses in the developing animal.
Effect of nafamostat mesilate on Na+ and K+ transport properties in the rabbit cortical collecting duct
Authors: Muto Shigeaki , Imai Masashi , Asano Yasushi 
Published: July 2012

To determine the mechanism(s) of hyperkalemia caused by nafamostat mesilate (NM), a serine‐protease inhibitor, we investigated the effects of the drug on Na+ and K+ transport properties of the collecting duct (CD) cell in the isolated and perfused cortical collecting duct from rabbit kidneys.
NM at 10−4 m in the lumen, hyperpolarized the apical membrane in parallel with increases in transepithelial resistance (RT) and fractional apical membrane resistance (fRA).
These effects were completely inhibited by pretreatment with 50 μm luminal amiloride, whereas they were not affected by luminal addition of 2 mm Ba2+.
NM at 10−4 m in the bath slightly but significantly depolarized the basolateral membrane without any changes in RT or fRA, although NM at 10−5 m in the bath had no effect on the electrical parameters.
It is concluded that NM mainly acts on the apical membrane of the CD cell and inhibits the amiloride‐sensitive Na+ conductance in the apical membrane.
Effects of KRN2391, nicorandil and diltiazem on the changes in the electrocardiogram caused by endothelin‐1 in anaesthetized rats
Authors: Harada Katsuhiko , Miwa Atsushi , Kaneta Soichiro , Izawa Toshio , Fukushima Hideaki , Ogawa Nobuyuki 
Published: July 2012

The effect of KRN2391, a novel vasodilator, on the changes of electrocardiogram caused by endothelin‐1 (ET‐1) was studied in anaesthetized rats and compared with the effects of nicorandil and diltiazem. In addition, the effect of KRN2391 on the action potential of guinea‐pig papillary muscle was studied.
The intracoronary administration (i.c.) of ET‐1 (5 μg) induced not only ST segment elevation of the electrocardiogram due to contraction of the coronary artery, but also arrhythmias involving atrioventricular block (A‐V block), ventricular premature contraction (VPC) and ventricular fibrillation (VF), and resulted in death in most animals. However, the administration of methacholine (3 μg, i.c.) produced ST segment elevation alone without developing arrhythmias.
Pretreatment with intravenous administration of KRN2391 (30 μg kg−1) inhibited the ST segment elevation and the development of arrhythmias induced by ET‐1, and decreased the incidence of death.
Nicorandil (1000 μg kg−1) prevented the ST segment elevation without suppression of the occurrence of VF. Diltiazem (100 μg kg−1) suppressed both the ST segment elevation and the occurrence of VF but not other arrhythmias. Nicorandil at 3000 μg kg−1 and diltiazem at 300 μg kg−1 produced not only a suppression of ST segment elevation and VF incidence but also a decrease in the occurrence of arrhythmias. These doses of nicorandil and diltiazem produced a decrease in death in a dose‐dependent manner.
KRN2391 (10 and 30 μg kg−1), nicorandil (1000 and 3000 μg kg−1) and diltiazem (100 and 300 μg kg−1) significantly decreased mean blood pressure in a dose‐dependent manner. Heart rate was decreased by nicorandil (3000 μg kg−1) and diltiazem (100 and 300 μg kg−1) but was not affected by KRN2391 (10 and 30 μg kg−1).
KRN2391 (30 μm) significantly shortened the action potential duration of guinea‐pig ventricle at 50% and 90% repolarization (APD50 and APD90). The effect of KRN2391 was inhibited by a K+ channel blocker, glibenclamide (30 μm).
These results suggest that the occurrence of ST segment elevation and arrhythmias induced by ET‐1 are due to a dual direct action on both coronary vascular smooth muscle and myocardium. Therefore, the protective effects of KRN2391, nicorandil and diltiazem on ET‐1‐induced heart disorders appear to be due to their direct actions on coronary vascular smooth muscle and the myocardium.
Intracellular cross‐talk between receptors coupled to phospholipase C via pertussis toxin‐sensitive and insensitive G‐proteins in DDT1MF‐2 cells
Authors: Dickenson John M. , Hill Stephen J. 
Published: July 2012

The effect on intracellular free calcium concentration ([Ca2+]i) of simultaneous activation of receptors coupled to phospholipase C via pertussis toxin (PTX)‐sensitive and ‐insensitive G‐proteins has been investigated in the hamster vas deferens smooth muscle cell line, DDT1MF‐2.
In fura‐2‐loaded DDT1MF‐2 cells, activation of adenosine A1‐receptors (which are linked to PTX‐sensitive G‐proteins) with a maximal concentration of N6‐cyclopentyladenosine (CPA; 300 nm) increased [Ca2+]i from 121 ± 5 nm to 254 ± 20 nm (n = 8). These experiments were performed in the presence of extracellular Ca2+. Stimulation of histamine H1‐receptors (which are linked to PTX‐insensitive G‐proteins) with a low concentration of histamine (1 μm) increased [Ca2+]i from 128 ± 8 nm to 150 ± 13 nm (n = 8). When combined, CPA (300 nm) and histamine (1 μm) synergistically raised [Ca2+]i from 134 ± 6 nm to 607 ± 61 nm (n = 8).
Removal of extracellular Ca2+ (experiments performed in Ca2+‐free buffer containing 0.1 mm EGTA) had no effect on the synergistic interaction between CPA (300 nm) and histamine (1 μm).
The addition of maximal concentrations of CPA (300 nm) and histamine (100 μm) resulted in a rise in [Ca2+]i which was additive when compared to the Ca2+ responses obtained with the two agonists alone. Low (30 nm) and subthreshold (3 nm) concentrations of CPA did not alter the Ca2+ response elicited by maximal concentrations of histamine (100 μm).
Subthreshold concentrations of CPA (3 nm) and low concentrations of histamine (1 μm) elicited synergistic rises in [Ca2+]i.
Synergistic Ca2+ responses were not observed between histamine H1‐ and ATP‐receptors when cells were simultaneously stimulated with either 1 μm or 10 μm of each agonist.
These data suggest that adenosine A1‐receptors linked to PTX‐sensitive G‐protein(s) and histamine H1‐receptors linked to PTX‐insensitive G‐proteins interact synergistically to raise [Ca2+]i. In contrast, activation of ATP‐receptors which are linked to PTX‐insensitive G‐protein(s) do not interact synergically with histamine H1‐receptors.
In vivo release of dopamine from rat striatum, substantia nigra and prefrontal cortex: differential modulation by baclofen
Authors: Santiago Marti , Machado Alberto , Cano Josefina 
Published: July 2012

The effect of baclofen, a GABAB receptor agonist, on the release of dopamine from the striatum (ST), substantia nigra (SN) and prefrontal cortex (PFC) of the rat was examined by intracerebral microdialysis.
Perfusion of baclofen 50 μm did not affect the striatal release of dopamine. However, dopamine release was markedly reduced in the SN and PFC.
3,4‐Dihydroxyphenylacetic acid and homovanillic acid output increased in the ST and decreased in the SN and PFC when baclofen was perfused through the microdialysis probe. 5‐Hydroxyindoleacetic acid levels were not affected in any experimental condition by baclofen perfusion.
The results suggest that GABAB receptors modulate the release of dopamine in the SN and PFC, but do not affect the striatal release of dopamine, which indicates that the role of GABA receptor activation is different in the dopaminergic terminals of the ST and PFC.
Species‐selective binding of [3H]‐idazoxan to α2‐adrenoceptors and non‐adrenoceptor, imidazoline binding sites in the central nervous system
Authors: Hussain J.F. , Kendall D.A. , Wilson V.G. 
Published: July 2012

We have used the imidazoline derivative [3H]‐idazoxan to define α2‐adrenoceptors and non‐adrenoceptor, imidazoline binding sites in cerebral cortex membranes of calf, mouse, rat, guinea‐pig and man.
Competition experiments using the selective α‐adrenoceptor drugs, rauwolscine and corynanthine, indicated that [3H]‐idazoxan bound to a single population of sites in the calf and mouse membranes. However, [3H]‐idazoxan also labelled non‐adrenoceptor, imidazoline binding sites in the rat (15%), guinea‐pig (30%) and human (40%) cerebral cortex membranes.
Competition experiments with adrenaline and cirazoline in the guinea‐pig cortex, verified [3H]‐idazoxan binding to both α2‐adrenoceptors and to non‐adrenoceptor, imidazoline binding sites.
It has been postulated by several groups that [3H]‐idazoxan may possess partial agonist activity. To investigate this further, saturation experiments were performed in the cerebral cortex membranes of all five species in the absence and presence of 300 μm guanosine triphosphate (GTP). GTP had no effect on [3H]‐idazoxan binding in guinea‐pig cerebral cortex; in both rat and mouse membranes 300 μm GTP increased the dissociation constant for [3H]‐idazoxan by 2–3 fold without significantly affecting the Bmax. GTP reduced the Bmax by approximately 30% and 60% in calf and human cerebral cortex membranes, respectively, without significantly altering the Kd.
Saturation experiments were performed in the calf cerebral cortex membranes in the absence and presence of 300 μm GTP with the selective α2‐adrenoceptor agonist [3H]‐clonidine and the selective muscarinic antagonist [3H]‐quinuclidinyl benzilate (QNB). GTP reduced the Bmax for [3H]‐clonidine without altering the Kd, but failed to affect either the Bmax or the Kd for [3H]‐QNB.
Saturation experiments were performed in human cerebral cortex membranes in the presence of α2‐adrenoceptor blockade with and without GTP. GTP 300 μm reduced the Bmax for [3H]‐idazoxan at the non‐adrenoceptor, imidazoline binding sites, without affecting the Kd. GTP did not affect [3H]‐QNB binding to muscarinic sites.
Thus, there is a need to investigate further the pharmacological actions of [3H]‐idazoxan in view of its ability to recognise both α2‐adrenoceptors and non‐adrenoceptor, imidazoline binding sites and because it might possess agonist activity at some of these sites.
Attenuation of contractions to acetylcholine in canine bronchi by an endogenous nitric oxide‐like substance
Authors: Gao Yuansheng , Vanhoutte Paul M. 
Published: July 2012

The involvement was assessed of an endogenous nitric oxide‐like substance in contractions of canine bronchi to acetylcholine.
Canine third order bronchial rings, in some of which the epithelium was removed mechanically, were suspended in organ chambers and isometric tension was recorded. In some experiments, the content of guanosine 3′,5′‐cyclic monophosphate (cyclic GMP) of the bronchi was also measured.
Acetylcholine induced concentration‐dependent contractions. The contractions were potentiated by nitro‐l‐arginine (an inhibitor of the synthesis of nitric oxide), oxyhaemoglobin (a scavenger of nitric oxide), and methylene blue (an inhibitor of soluble guanylate cyclase). The magnitude of the potentiation to acetylcholine‐induced contractions by these inhibitors were not significantly different between tissues with and without epithelium.
Acetylcholine induced a concentration‐dependent increase in intracellular content of cyclic GMP, which was similar in bronchi with and without epithelium. These increases were abolished by nitro‐l‐arginine and methylene blue.
During contractions to acetylcholine, exogenous nitric oxide relaxed the canine bronchi. The relaxations were not affeced by nitro‐l‐arginine, but were augmented by superoxide dismutase plus catalase, and were abolished by methylene blue.
These observations suggest that, during contraction evoked by acetylcholine, the production of an endogenous nitric oxide‐like substance increases and in turn attenuates the response of the airways to the muscarinic agonist. However, the endogenous nitric oxide‐like substance does not play a major role in the epithelium‐dependent attenuation of the contraction to acetylcholine in canine bronchi.
Characterization of CCK receptors in a novel smooth muscle preparation from the guinea‐pig stomach by use of the selective antagonists CI‐988, L‐365,260 and devazepide
Authors: Boyle Stephen J. , Tang Kim‐Wah , Woodruff Geoffrey N. , McKnight Alexander T. 
Published: July 2012

The cholecystokinin receptors mediating motor responses in a novel smooth muscle preparation from the corpus region of the guinea‐pig stomach have been characterized by use of five agonist peptides and the antagonists CI‐988, L‐365,260 and devazepide.
Mucosa‐denuded strips of circular muscle were contracted in a concentration‐dependent manner by the five cholecystokinin (CCK)‐related peptides CCK‐8S, pentagastrin, gastrin‐I, CCK‐8US and CCK‐4.
CI‐988 was a powerful antagonist of the response to pentagastrin with an affinity (pKB = 9.49) similar to that obtained in CCKB receptor binding assays. With CCK‐8S as the agonist, CI‐988 was approximately 1000 fold less powerful as an antagonist.
Devazepide powerfully blocked responses to CCK‐8S with an affinity (pKB = 9.54) that was in agreement with reported functional data obtained in pancreatic amylase secretion studies, a system exhibiting CCKA receptor activity. Devazepide displayed lower affinity against pentagastrin than against CCK‐8S.
CI‐988 blocked responses to pentagastrin in an insurmountable manner in the presence of 3 nm devazepide; a concentration previously shown to block the CCKA receptor. The nature of the antagonism observed with L‐365,260 was unaltered by the presence of devazepide.
The guinea‐pig stomach corpus smooth muscle preparation contains both subtypes of CCK receptor and will be useful as a pharmacological tool for investigating the functional effects of novel CCK ligands.
Comparative study of the control of basal acid output from rodent isolated stomachs
Authors: Welsh Nicola J. , Shankley Nigel P. , Black James W. 
Published: July 2012

Isolated, lumen‐perfused, whole stomach preparations from mouse and immature rat produced a stable basal acid output which, although not blocked by histamine H2‐, acetylcholine M‐ or CCKB/ gastrin receptor antagonists, was almostly completely blocked by the H+/K+‐ATPase inhibitor, omeprazole, and the metabolic inhibitor, sodium thiocyanate (NaSCN).
Fully‐defined concentration‐effect curves could be obtained on both assays with the phosphodiesterase inhibitor, isobutyl methylxanthine (IBMX) and with dibutyryl cyclic AMP.
On the rat stomach assay, histamine H2‐receptor blockade had no effect on the IBMX curve. In contrast, the IBMX response in the mouse was abolished by histamine H2‐receptor blockade. On both assays responses to dibutyryl cyclic AMP were resistant to H2‐receptor blockade.
In the absence of suprathreshold endogenous histamine, it is argued that H+/K+‐ATPase mediated basal acid secretion from the mouse stomach assay is regulated by something other than cyclic AMP.
Effect of extracellular ATP on contraction, cytosolic calcium activity, membrane voltage and ion currents of rat mesangial cells in primary culture
Authors: Pavenstädt Hermann , Gloy Joachim , Leipziger Jens , Klär Bettina , Pfeilschifter Josef , Schollmeyer Peter , Greger Rainer 
Published: July 2012

The effects of extracellular ATP on contraction, membrane voltage (Vm), ion currents and intracellular calcium activity [Ca2+]i were studied in rat mesangial cells (MC) in primary culture.
Addition of extracellular ATP (10−5 and 10−4 m) to MC led to a cell contraction which was independent of extracellular calcium.
Membrane voltage (Vm) and ion currents were measured with the nystatin patch clamp technique. ATP induced a concentration‐dependent transient depolarization of Vm (ED50: 2 × 10−6 m). During the transient depolarization ion currents were monitored simultaneously and showed an increase of the inward‐ and outward current.
In a buffer with a reduced extracellular chloride concentration (from 145 to 30 mm) ATP induced a depolarization augmented to −4 ± 4 mV.
ATP‐γ‐S and 2‐methylthio‐ATP depolarized Vm to the same extent as ATP, whereas α,β‐methylene‐ATP (all 10−5 m) had no effect on Vm.
The Ca2+ ionophore, A23187, depolarized Vm transiently from −51 ± 2 to −28 ± 4 mV and caused an increase of the inward current.
The intracellular calcium activity [Ca2+]i was measured with the fura‐2 technique. ATP stimulated a concentration‐dependent increase of [Ca2+]i (ED50: 5 × 10−6 m). The increase of [Ca2+]i was biphasic with an initial peak followed by a sustained plateau.
The [Ca2+]i peak was still present in an extracellular Ca2+‐free buffer, whereas the plateau was abolished. Verapamil (10−4 m) did not inhibit the [Ca2+]i increase induced by ATP.
The data indicate that extracellular ATP contracts MC and is able to increase [Ca2+]i by the release of Ca2+ from intracellular stores and recruitment from the extracellular space. In addition ATP depolarizes Vm of MC by activating a Cl− conductance. The ATP‐induced depolarization is mediated by a P2y receptor.