bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of treatment with cholecalciferol on the membrane potential and contractility of aortae from spontaneously hypertensive rats
Authors: Silva Eneida G. , Vianna Lucia M. , Okuyama Paulo , Paiva Therezinha B. 
Published: July 2012

The diet of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NWR) was supplemented with 12.5 μg cholecalciferol per 100 g body weight daily, by gavage, for 4 weeks.
The amplitude of the contractile responses of aortic rings from SHR to potassium and adrenaline, which was smaller than in NWR aortae, was increased after treatment with cholecalciferol. No further changes were observed in the responses of NWR and SHR aortae in the presence of 100 nM apamin.
The membrane potentials of aortae from SHR, which were higher than those of aortae from NWR, decreased after treatment with cholecalciferol. Further depolarization was observed in aortic rings from NWR, but not in aortic rings from SHR, after their preincubation with 100 nM apamin.
It is concluded that cholecalciferol normalizes the membrane potential and contractility of aortae from SHR, probably through an effect on lipid composition and structure of the plasma membrane.
Effect of endothelin antagonists on the responses to prostanoid endothelium‐derived contracting factor
Authors: Moreau Pierre , Takase Hiroyuki , Lüscher Thomas F. 
Published: July 2012

The effect of endothelin antagonists on endothelium‐dependent contractions was studied in conditions of stimulated endothelium‐derived contracting factor (EDCF) release and with exogenous activation of thromboxane A2‐endoperoxide receptors in the rat aorta.
The incubation of aortic rings with Nω‐nitro‐L‐arginine methyl ester (L‐NAME) led to EDCF‐mediated contraction upon stimulation with acetylcholine (24 ± 3% of KCl contraction). When vessels were preincubated with bosentan, an endothelinA‐ and endothelinB‐receptor antagonist, in addition to L‐NAME, acetylcholine‐induced contraction was reduced to 8 ± 2% (P < 0.01) of KCl contractions. PD147953, a selective endothelinA‐receptor antagonist, reduced the contraction to 14 ± 4% (P < 0.05) of KCl contractions.
Bosentan preincubation produced a significant parallel rightward shift of the contractions to U46619, a selective thromboxane A2 receptor agonist. In contrast, PD147953 failed to exhibit any inhibitory effect on U46619 contractions.
These results suggest that endothelin antagonists inhibit EDCF‐mediated contractions by blocking endothelinA receptors and that, in addition, bosentan antagonizes the direct stimulation of thromboxane A2 receptors.
Block by N6‐L‐phenylisopropyl‐adenosine of the electrophysiological and morphological correlates of hippocampal ischaemic injury in the gerbil
Authors: Domenici M.R. , de Carolis A. Scotti , Sagratella S. 
Published: July 2012

The effects of the mixed A1 and A2 adenosine receptor agonist N6‐L‐phenyl‐isopropyladenosine (L‐PIA) were tested on ischaemia‐induced hippocampal neuronal injury in gerbils subjected to 5‐min bilateral carotid occlusion. For comparison, the effects of the selective A2 adenosine receptor agonist, CGS 21680 were tested.
Five‐min bilateral carotid occlusion produced within 1 week an irreversible suppression of the CA1, but not of the dentate extracellular electrical somatic responses, in 30% of gerbil hippocampal slices with respect to controls. In addition, a significant reduction occurred in the density of CA1 hippocampal pyramidal neurones but not of dentate granule cells with respect to controls.
Injection 1 h before or after bilateral carotid occlusion of L‐PIA (0.8‐1.5 mg kg−1, i.p.) but not of CGS 21680 (5 mg kg−1, i.p.), significantly prevented the irreversible disappearance of the CA1 extracellular electrical somatic responses with respect to controls. In addition, the CA1 pyramidal neuronal loss was also prevented.
The results show that activation of A1 adenosine receptors is able to prevent or block the electrophysiological and morphological correlates of hippocampal neuronal injury after global ischaemia in the gerbil, suggesting that adenosine receptor agonists might have a useful role in the treatment of neuronal functional and anatomical injury due to ischaemia.
Pharmacological characterization of desensitization in a human mGlulα‐expressing non‐neuronal cell line co‐transfected with a glutamate transporter
Authors: Desai Manisha A. , Burnett J. Paul , Mayne Nancy G. , Schoepp Darryle D. 
Published: July 2012

Stimulation of phosphoinositide hydrolysis by human mGlu1α (HmGlu1α) was examined in a non‐neuronal cell line (AV12‐664) co‐expressing both HmGlu1α and a rat glutamate/aspartate transporter (GLAST).
Desensitization of HmGlu1α could be elicited by inhibition of the GLAST transporter with the glutamate uptake inhibitor, L‐trans‐pyrrolidine‐2, 4‐dicarboxylic acid (trans‐PDC). Maximal inhibition of HmGlu1α‐mediated phosphoinositide hydrolysis was induced upon 24 h pretreatment with trans‐PDC. The concentration of glutamate in the extracellular medium also rose significantly in cells pretreated with trans‐PDC. Glutamate levels increased upon incubation with trans‐PDC in a time‐dependent manner, with maximal glutamate levels attained after 24 h incubation with trans‐PDC.
The time required for desensitization of HmGlu1α by trans‐PDC was compared to the time course for desensitization elicited by the direct‐acting mGlu receptor agonists, 1‐aminocyclopentane‐1S, 3R‐dicarboxylic acid (1S, 3R‐ACPD) and (R, S)‐3, 5‐dihydroxyphenylglycine (3, 5‐DHPG). Both direct‐acting mGlu receptor agonists elicited desensitization of HmGlu1α more rapidly than did trans‐PDC, with maximal inhibition of agonist‐induced phosphoinositide hydrolysis upon 12 h pretreatment. Agonist‐induced desensitization could be fully reversed upon washout of agonist for 12 h.
Both mGlu receptor agonist‐ and trans‐PDC‐induced desensitization of HmGlu1α could be blocked by inclusion of (+)‐α‐methyl‐4‐carboxyphenylglycine (MCPG), an mGlu receptor antagonist, in the pretreatment medium.
Agonist‐stimulated phosphoinositide hydrolysis by HmGlu1α was found to parallel closely agonist‐induced desensitization of HmGlu1α. Thus, the EC50 values for 1S, 3R‐ACPD‐ and 3, 5‐DHPG‐stimulated phosphoinositide hydrolysis were similar to the EC50 values for eliciting desensitization of HmGlu1α.
These studies demonstrate desensitization of recombinant human mGlu1α receptor in a non‐neuronal cell line in which the receptor can be regulated by direct activation or by manipulation of glutamate transporter activity. Desensitization of HmGlu1α was found to be mediated by activation of the receptor since the mGlu receptor antagonist, MCPG, blocked both mGlu receptor agonist‐ and trans‐PDC‐induced desensitization of HmGlu1α. Furthermore, agonist‐induced desensitization of HmGlu1α was found to parallel receptor‐mediated stimulation of phosphoinositide hydrolysis.
Extracellular site for econazole‐mediated block of Ca2+ release‐activated Ca2+ current (Icrac) in T lymphocytes
Authors: Christian Edward P. , Spence Katherine T. , Togo James A. , Dargis Pauline G. , Warawa Edward 
Published: July 2012

Standard whole cell patch clamp recording techniques were used to study the pharmacological characteristics and site of econazole‐mediated inhibition of calcium release‐activated calcium current (Icrac) in the human leukaemic T cell line, Jurkat.
Extracellularly applied econazole blocked Icrac in a concentration‐dependent manner (IC50 ≅ 14 μm). Block developed over a relatively slow timecourse of 30–60 s (10 μm), and only partially reversed over minutes.
Econazole dialysed from the pipette into the cytosol at concentrations ranging from 0.1 to 30 μm did not reduce Icrac, or quantitatively affect Icrac block by extracellularly applied econazole.
A less lipophilic quaternary iodide derivative of econazole was synthesized to retard absorption through the cell membrane. When applied extracellularly, this compound blocked Icrac in a concentration‐dependent manner with onset kinetics comparable to econazole.
Results with intracellularly dialysed econazole and the quaternary econazole derivative provide convergent evidence that econazole blocks Icrac via an extracellular interaction.
The inability of intracellularly applied econazole to inhibit Icrac argues against the notion that econazole inhibits capacitative Ca2+ entry pathways secondary to its known inhibitory effects on cytochrome P‐450.
Ionic mechanisms contributing to the vasorelaxant properties of iodinated contrast media: a comparison of iohexol and iodixanol in the rabbit isolated aorta
Authors: Pitman M.R. , Karlsson J.O.G. , Griffith T.M. 
Published: July 2012

We have used rings of rabbit thoracic aorta to investigate the vasorelaxant properties of two different classes of non‐ionic iodinated radiographic contrast media (IRCM) and the mechanisms, underlying their mode of action. Iohexol (a triiodinated monomer) was compared with iodixanol (a hexaiodinated dimer).
Iohexol and iodixanol both relaxed phenylephrine (0.3 μm) constricted rabbit aorta in a concentration‐dependent manner that did not depend on the presence of an intact endothelium. When expressed as a function of iodine concentration, iodixanol caused significantly less relaxation than iohexol. However, the extent of relaxation was similar for both IRCM when expressed on a molar basis. Furthermore, increasing the molarity of the buffer to comparable levels with mannitol evoked only a small (∼ 15%) relaxation of phenylephrine‐induced tone.
Ouabain (10 μm) significantly inhibited both iohexol‐ and iodixanol‐induced relaxations by ∼30%. 5‐(N‐Ethyl‐N‐isopropyl)‐amiloride (EIPA, 100 nM) significantly inhibited iohexol‐induced relaxation to the same extent as ouabain, but did not alter the vasorelaxant effect of iodixanol. Co‐incubation with ouabain and EIPA had an additive effect in the case of iohexol, increasing inhibition of relaxation to ∼60%, whereas inhibition of iodixanol‐induced relaxation by the combination of ouabain plus EIPA did not differ from that of ouabain alone.
Replacing NaCl with N‐methyl‐D‐glucamine (NMDG) to lower extracellular [Na+] and thereby inhibit Na+‐Ca2+ exchange, attenuated the relaxation evoked by iohexol or by iodixanol (by ∼25%) in each case.
We conclude that iohexol‐ and iodixanol‐induced vasorelaxation in rabbit aorta is mediated through a direct action on vascular smooth muscle that is not simply a consequence of altered osmolality. It involves modulation of the Na+‐K+ ATPase and, in the case of iohexol, Na+‐H+ exchange. Both agents also appear to modulate Na+‐Ca2+ exchange, through direct and/or indirect mechanisms. This is the first study to show specific pharmacological differences between monomeric and dimeric contrast media in vascular smooth muscle.
Long Ca2+ channel opening induced by large depolarization and Bay K 8644 in smooth muscle cells isolated from guinea‐pig detrusor
Authors: Nakayama S. , Brading Alison F. 
Published: July 2012

In smooth muscle cells enzymatically isolated from guinea‐pig urinary bladder, Ca2+ channel currents were recorded by conventional cell‐attached patch clamp techniques. In most recordings Bay K 8644 (2 μm) was contained in the patch pipette.
Closure of Ca2+ channels observed during the repolarizing steps was significantly slowed by preconditioning with large depolarizations (+80 and 100 mV), with or without Bay K 8644 in the pipette.
The sum of the unitary Ca2+ channel current traces obtained after large conditioning depolarizations (in the presence of Bay K 8644) showed a slowly deactivating tail current.
By use of this slow deactivating feature, the current‐voltage relationship of the unitary Ca2+ channel current was continuously measured with a ramp pulse after large depolarization. The slope conductance ranged from 22 to 30 pS, compatible with that of L‐type Ca2+ channels.
It is concluded that L‐type Ca2+ channels in guinea‐pig detrusor cells are open for much longer after large depolarizations consistent with their being two channel open states, and that Bay K 8644 prolongs the lifetime of both open states. The underlying mechanisms are discussed.
Endothelial modulation of α1‐adrenoceptor contractile responses in the tail artery of spontaneously hypertensive rats
Authors: Tabernero Antonia , Giraldo Jesús , Vivas Nuria María , Badia Albert , Vila Elisabet 
Published: July 2012

Vascular contraction induced by phenylephrine was studied in tail artery rings from spontaneously hypertensive (SHR) and Wistar Kyoto rats (WKY) with particular focus on the role of endothelium. The influence of receptor reserve and the density of α1‐adrenoceptors on the possible differences observed were also analysed.
Phenylephrine (0.01–100 μm) induced concentration‐dependent vasoconstrictions. The maximum response (α, P < 0.001) was greater but the pEC50 (P < 0.05) smaller in rings from SHR than from WKY rats irrespective of the presence or absence of endothelium.
Removal of endothelial cells resulted in a decrease of the maximum contraction with no modification in the pEC50 in arteries from both WKY and SHR.
The density of α1‐adrenoceptors (Bmax) and the dissociation constant (KD) were found to be the same for preparations from SHR and WKY rats in [3H]‐prazosin binding experiments.
The apparent affinity (pKA) determined by the nested hyperbolic method and the operational model was similar in tail arteries from the two rat strains, irrespective of the presence or absence of endothelium. However, in endothelium‐denuded rings, the pKA value was enhanced when compared with intact rings, in both SHR and WKY rats.
In rings from hypertensive rats, the operational parameter maximum possible effect (Em) was greater and the agonist efficacy (τ) was smaller than in rings from normotensive rats. When the endothelium was removed log τ and Em diminished in preparations from both rat strains.
In summary, the increased maximum responsiveness to phenylephrine in rings from SHR could be due to enhancement in Em. The log τ values indicate a deterioration in the transduction of the stimulus provided by the agonist in tail arteries from hypertensive animals. This study also suggests that the absence of endothelium modifies the α1‐adrenoceptor‐mediated vasocontriction probably by altering the transduction signalling mechanisms. The importance of analysing the degree of endothelium functionality when comparing results from different groups of rats is stated.
Effect of intracerebroventricular and intravenous administratioi of nitric oxide donors on blood pressure and heart rate in anaesthetized rats
Authors: Nurminen Marja‐Leena , Vapaatalo Heikki 
Published: July 2012

The effects of nitric oxide (NO) releasing substances, sodium nitroprusside, 3‐morpholino sydnonimine (SIN‐1) and a novel oxatriazole derivative, GEA 3162, on blood pressure and heart rate were studied after peripheral or central administration in anaesthetized normotensive Wistar rats.
Given as cumulative intravenous injections, both nitroprusside and GEA 3162 (24–188 nmol kg−1) induced short‐lasting and dose‐dependent decreases in mean arterial pressure, while SIN‐1 decreased blood pressure only slightly even after larger doses (94–3000 nmol kg−1). Heart rate increased concomitantly with the hypotensive effect of the NO‐releasing substances.
Cumulative intracerebroventricular administration of GEA 3162 (24–188 nmol kg−1) induced a dose‐dependent hypotension with slight but insignificant increases in heart rate. In contrast, intracerebroventricular nitroprusside induced little change in blood pressure, while a large dose of SIN‐1 (3000 nmol kg−1, i.c.v.) slightly increased mean arterial pressure. However, intracerebroventricular nitroprusside and SIN‐1 increased heart rate at doses that did not significantly affect blood pressure.
To determine whether the cardiovascular effects of GEA 3162 were attributable to an elevation of cyclic GMP levels, pretreatments with methylene blue, a putative guanylate cyclase inhibitor, were performed. This substance failed to attenuate the cardiovascular effects of peripherally or centrally administered GEA 3162, suggesting that the effects were independent of guanylate cyclase.
In conclusion, the centrally administered NO‐donor, GEA 3162, induced a dose‐dependent hypotensive response without significant changes in heart rate. Furthermore, intracerebroventricular injections of nitroprusside and SIN‐1 increased heart rate without affecting blood pressure. These results suggest that NO released by these drugs may affect central mechanisms involved in cardiovascular regulation independently of cyclic GMP.
Modulation by extracellular ATP of L‐type calcium channels in guinea‐pig single sinoatrial nodal cell
Authors: Qi Ai‐Dong , Kwan Yiu Wa 
Published: July 2012

The effects of extracellular adenosine 5′‐triphosphate ([ATP]0) on the L‐type Ca2+ channel currents in guinea‐pig single sinoatrial nodal (SAN) cells, isolated by enzymatic dissociation, were investigated by use of whole‐cell patch‐clamp techniques.
The application of [ATP]0 (2 μm‐1 mM) produced an inhibitory effect on the L‐type Ca2+ channel current peak amplitude (10 mM Ba2+ as charge carrier) in a concentration‐dependent and reversible manner with an IC50 of 100 μm and a Hill coefficient of 1.83.
The presence of the adenosine receptor antagonists, 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX, 0.1 μm) and 8‐phenyltheophylline (10 μm) did not affect the [ATP]O‐induced inhibition of the Ca2+ channel currents. Adenosine (100 μm) had little effect on the basal Ca2+ channel currents. Adenosine 500 μm, caused 23% inhibition of the Ca2+ channel current, which was abolished by 0.1 μm DPCPX.
The presence of the P2‐purinoceptor antagonists, suramin (1, 10 and 100 μm), reactive blue 2 (1 and 10 μm) and pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS, 50 and 100 μm) failed to affect the inhibitory action of [ATP]0 on Ca2+ channel currents.
The relative rank order of potency of different nucleotides and nucleosides, at a concentration of 100 μm, on the inhibition of the Ca2+ channel currents is as follows: adenosine 5′‐triphosphate (ATP) = α, β‐methylene‐ATP (α, βMeATP) > > 2‐methylthioATP (2‐MeSATP) ≥ adenosine 5′‐O‐(3‐thiotriphosphate) (ATPγS) > > uridine 5′‐triphosphate (UTP) = adenosine 5′‐diphosphate (ADP) > adenosine 5′‐monophosphate (AMP) ≥ adenosine.
These results suggest that [ATP]0 may play an important role in the heart beat by inhibiting the L‐type Ca2+ channel currents in single SAN cells. This inhibitory effect is not due to the formation of adenosine resulting from the enzymatic degradation of [ATP]0. Based on the relative order of inhibitory potency of different nucleotides and nucleosides on the L‐type Ca2+ channel currents and the ineffectiveness of the purinoceptor antagonists tested, a novel type of purinoceptor may be involved.
Mediation by nitric oxide of the indirect effects of adenosine on calcium current in rabbit heart pacemaker cells
Authors: Shimoni Y. , Han X. , Severson D. , Giles W.R. 
Published: July 2012

Adenosine (ADO) is a potent negative chronotropic agent in the mammalian myocardium. We have used single myocytes from rabbit sino‐atrial node (SAN) to examine whether nitric oxide (NO) is a significant mediator of the effects of ADO on the pacemaker activity, or the underlying Ca2+ and K+ currents.
SAN pacemaker cells were isolated from rabbit hearts by enzymatic dispersion, and Ca2+ and K+ currents were recorded by the nystatin‐perforated patch voltage clamp method. ADO was applied in the presence of the β‐adrenoceptor agonist, isoprenaline (Iso) to mimic the adrenergic tone which the SAN is subjected to in vivo
Control experiments confirmed that isolated SAN cells responded to ADO (10–100 μm) with the expected (i) small increase in background inwardly rectifying K+ current, IK‐ADOi and (ii) pronounced decrease in L‐type Ca2+ current, ICa‐L These effects were mimicked by a selective A1 purinoceptor agonist, N6‐cyclopentyladenosine (CPA, 10 μm); and were inhibited following bath application of the antagonist, DPCPX (10 μm), which selectively blocks A1 purinoceptors. DMPX (10 μm), a blocker of A2 purinoceptor, had no effect on the actions of ADO.
A nitric oxide synthase inhibitor, L‐NMMA (100 μm), abolished the inhibitory effect of ADO on ICa‐L but did not alter activation of IK‐ADO After L‐NMMA washoff, it was possible to obtain the normal response (inhibition) of ICa‐L to ADO in the same cell.
To evaluate whether the observed effect of nitric oxide (NO) on ICa‐L was mediated by an increase in guanylyl cyclase (GC) activity and cyclic GMP formation, the guanylyl cyclase inhibitor, LY 83583 (40 μm) was applied prior to ADO. Under these conditions, the inhibitory effect of ADO on ICa‐L was abolished, but the activation of IK‐ADO was still observed.
In combination, these findings strongly suggest that in mammalian primary pacemaker tissue which is under adrenergic tone, the effects of ADO on ICa‐L are mediated by NO.
Effects of adrenomedullin and calcitonin gene‐related peptide on airway and pulmonary vascular smooth muscle in guinea‐pigs
Authors: Pinto Arthur , Sekizawa Kiyohisa , Yamaya Mutsuo , Ohrui Takashi , Jia Yu Xia , Sasaki Hidetada 
Published: July 2012

The airway and pulmonary vascular effects of adrenomedullin were studied in the guinea‐pig isolated trachea, main bronchi and pulmonary artery in vitro and compared to the effects of calcitonin gene‐related peptide (CGRP).
In tracheal rings, CGRP (1 nM to 1 μm) potentiated the cholinergic contractions induced by electrical field stimulation (EFS) at 5 Hz in a concentration‐dependent manner. At a concentration of 1 μm, CGRP slightly decreased the responses to log EFS frequency, producing 50% of the maximum contraction from a control value of 0.77 ± 0.10 Hz to 0.54 ± 0.05 Hz without a significant effect on the concentration‐response curves to acetylcholine (ACh). In contrast, adrenomedullin (1 nM to 1 μm) did not alter either EFS‐induced cholinergic or ACh‐induced contractions.
In bronchial strips, CGRP (1 nM to 1 μm) slightly reduced both the non‐adrenergic non‐cholinergic (NANC) contraction induced by EFS at 10 Hz and the substance P (1 μm)‐induced contraction in a concentration‐dependent manner, whereas adrenomedullin (1 nM to 1 μm) was without effect.
Neither CGRP (1 μm) nor adrenomedullin (1 IXM) altered NANC relaxation induced by EFS at 5 Hz in tracheal rings precontracted with histamine (10 μm).
Adrenomedullin (1 nM to 1 μm) and CGRP (1 nM to 1 μm) induced a concentration‐dependent relaxation of the histamine (10 μm)‐ and prostaglandin F2α (10 μm)‐precontracted pulmonary arterial rings with intact endothelium with a similar potency.
Neither removal of the endothelium nor NG‐nitro‐L‐arginine methyl ester (100 μm) altered the vasorelaxant effects of adrenomedullin (1 nM to 1 μm) and CGRP (1 nM to 1 μm).
The putative CGRP receptor antagonist, CGRP8–37 (1 μm to 10 μm) concentration‐dependently attenuated the CGRP (3 nM to 30 nM)‐induced vasorelaxant actions, whereas it had no effect on the relaxation of vessel rings induced by adrenomedullin (3 nM to 30 nM).
These results suggest that adrenomedullin is a potent vasodilator of the pulmonary artery without any bronchomotor effect in the guinea‐pig lung, and that the vasorelaxant actions of adrenomedullin are not mediated via the activation of CGRP1 receptors.