bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of tert‐butyl‐benzohydroquinone, a putative SR Ca2+ pump inhibitor, on isometric relaxation during the staircase in the rabbit and rat ventricle
Authors: Baudet S. , Noireaud J. , Le Marec H. , Khammari A. 
Published: July 2012

The effects of 2,5 di‐(tert‐butyl)‐1,4‐benzohydroquinone (TBQ), a putative inhibitor of the sarcoplasmic reticulum Ca2+ pump, on mechanical relaxation and contraction‐relaxation coupling have been studied at different frequencies (0.5‐3 Hz) in isometrically contracting isolated right ventricular preparations of rabbit and rat at 37°C. Two types of mechanical responses have been studied: the twitch tension and the force transient (rewarming spike, RSp) following a rapid cooling contracture (RCC, an index of sarcoplasmic reticulum Ca2+ content) on return to 37°C.
The coupling between contraction and relaxation was assessed by two methods: (a) by evaluation of the variation of the slope relating the maximal rate of tension fall to twitch peak tension; (b) by modelling the twitch according to the following equation: TwT (t) = C x(t/A)Bx exp(1‐(t/AB) where TwT(t) is the time course of isometric tension, t is time, C and A are an inotropic and a chronotropic index respectively and B, a contraction‐relaxation coupling index (Nwasokwa, 1993).
In the rabbit ventricle, 30 μm TBQ did not prevent the frequency‐induced shortening of the twitch time to half‐relaxation (t1/2) and of the time constant (τ) describing the final part of the RSp relaxation (τ decreased from 140 ms (0.5 Hz) to 133 ms (3 Hz) in control and from 253 ms (0.5 Hz) to 197 ms (3 Hz) after exposure to TBQ). By contrast, at a given frequency, the prolongation of relaxation induced by TBQ was proportional to its inotropic effect (unchanged slopes and B values) but TBQ did not prevent the acceleration of relaxation observed at high frequencies: B increased from 2.02 (0.5 Hz) to a peak value of 2.18 (1 Hz) in control and from 1.88 (0.5 Hz) to a maximum of 2.48 (2 Hz) after TBQ exposure. TBQ significantly attenuated the decay of RCCs elicited after increasingly longer periods of muscle quiescence as normally observed in control conditions.
In the rat ventricle, TBQ depressed relaxation more than expected on the basis of its negative inotropic effects (B decreased from 2.16 to 1.84 at 0.5 Hz and from 2.15 to 1.66 at 3 Hz). TBQ also slowed the rate of RSp relaxation (τ increased from 95 ms to 168 ms at 0.5 Hz, and from 109 ms to 149 ms at 3 Hz) and increased twitch t1/2. By contrast with the results obtained in the rabbit ventricle, B, τ and t1/2 were frequency‐insensitive whether or not TBQ was present.
TBQ exerts negative inotropic effects consistent with inhibition of the SR Ca2+ pump. In the rabbit ventricle, the TBQ‐induced potentiation of relaxation acceleration at high pacing frequencies suggests the involvement of counteracting Ca2+‐mediated mechanisms probably via Ca2+‐calmodulin‐activated kinases. In the rat ventricle, TBQ did not have any differential effect on relaxation depending on the frequency, probably because the extent of the negative staircase was small in the present experimental conditions.
Enhanced vasocontraction of rat tail arteries by toxoflavin
Authors: Wang Zunzhe , Ma Meisheng , Wang Rui 
Published: July 2012

It has been suggested that the toxic effect of toxoflavin (TXF) produced by Pseudomonas cocovenenas is mainly due to the impairment of electron transfer of the mitochondrial respiratory chain. However, the cardiovascular effect of TXF is unknown. In the present study, the effect of TXF on the isometric contraction of rat isolated tail artery strips and the underlying mechanisms were investigated.
The basal force of the tissues was not affected by the toxin. However, the application of TXF before or during KC1 (60 mM) stimulation potentiated KC1‐induced vasocontraction, specifically the tonic phase of the contraction.
When the vessel strips were precontracted with phenylephrine (Phe), TXF further enhanced the tonic contraction of the tissue. Pretreatment of tissues with TXF also potentiated subsequent vasocontraction induced by Phe. The vasocontractor effects of TXF and Phe, however, were not additive.
The vascular effect of TXF was not mediated by oxygen‐derived free radicals since catalase and SOD did not affect TXF‐enhanced vasocontraction. In contrast, the vasocontractor effect of TXF was dependent on extracellular Ca2+ and abolished by nifedipine (a Ca2+ antagonist). TXF also had no effect on caffeine‐ or U46619‐induced vasocontraction.
It is suggested that TXF may potentially contract blood vessels via its effect on Ca2+ channels. This effect of TXF depends on the contractile status of the vascular tissues.
Involvement of nitric oxide, but not prostaglandins, in the vascular sympathoinhibitory effects of losartan in the pithed spontaneously hypertensive rat
Authors: Richer Christine , Domergue Valérie , Vincent Marie‐Pascale , Giudicelli Jean‐François 
Published: July 2012

The aim of this study was to investigate whether nitric oxide (NO) and/or vasodilator prostaglandins (PGs) are involved in the sympathoinhibitory effects exerted by losartan versus the vascular responses elicited by spinal cord electrical stimulation (SCS) in pithed spontaneously hypertensive rats (SHRs).
SHRs were given orally and for 8 days either losartan (10 mg kg−1 daily) or distilled water (controls). After pithing, blood pressure, heart rate, cardiac output, renal and muscular blood flows (pulsed Doppler technique) and the corresponding vascular resistance values were measured or calculated at baseline. Then, animals from both groups were given i.v. either saline, or NG‐nitro‐L‐arginine methyl ester (L‐NAME, 1 mg kg−1), or diclofenac (4 mg kg−1). Thereafter, haemodynamic parameters were determined in the six subgroups of animals in response (a) to SCS at increasing frequencies, and (b) to a noradrenaline bolus injection.
Losartan significantly decreased mean arterial pressure as well as renal and total peripheral resistances. In addition, losartan exhibited strong vascular sympathoinhibitory effects, significantly decreasing the systemic pressor and regional vasoconstrictor responses to SCS, but did not affect those to exogenous noradrenaline. In contrast, SCS‐induced tachycardia was not modified by losartan.
L‐NAME significantly increased total peripheral and regional vascular resistances but did not affect blood pressure and heart rate basal values. L‐NAME potentiated the haemodynamic responses to SCS in control and, to a larger extent, in losartan‐treated SHRs so that, with the exception of the renal vascular bed, the sympathoinhibitory effects of losartan were attenuated in all vascular beds studied. L‐Arginine (300 mg kg−1) caused reversal of L‐NAME effects in both control and losartan‐treated SHRs.
Diclofenac did not affect the basal values of haemodynamic parameters in control and losartan‐treated SHRs. Diclofenac potentiated the pressor and vasoconstrictor responses to SCS and to a similar extent, in both control and losartan‐treated SHRs, so that the sympathoinhibitory effects of losartan were fully maintained.
These results demonstrate that in pithed SHRs: (a) NO but not PGs contribute to the basal vasomotor tone, (b) both NO and PGs attenuate the pressor and vasoconstrictor responses to SCS, (c) NO plays a major role in the vascular sympathoinhibitory effects of losartan, except at the renal level, and (d) endogenous PGs are not involved in these sympathoinhibitory effects.
Vascular reactivity in mesenteric resistance arteries following chronic nitric oxide synthase inhibition in Wistar rats
Authors: Dowell Fiona J. , Henrion Daniel , Duriez Micheline , Michel Jean‐Baptiste 
Published: July 2012

Chronic inhibition of nitric oxide synthase (NOS) induces a sustained hypertension in rats. We studied the effects of chronic inhibition on the in vitro vasoreactivity of mesenteric resistance arteries in Wistar rats. We also investigated the effects of acute in vitro NOS inhibition in these vessels.
Acute NOS inhibition (Nω‐nitro‐L‐arginine, L‐NOARG, 10 μm) had no effect on the contractile response to KCl (125 mM), enhanced the response to the phorbol ester, phorbol dibutyrate (1 μm; 69±9% of KCl response, n=6; 38±7% control, n=6, P<0.05), increased sensitivity to phenylephrine (EC50: 1.68±0.14 μm, n=5; 2.35±0.23 μm control, n=5, P<0.05) and sodium nitroprusside (SNP; EC50 1.79±0.61 nM, n=6; 20.44±6.87 μm control, n=6, P<0.05) and decreased sensitivity to acetylcholine (EC50 123±12 nM, n=6; 45±10 nM control, n=13, P<0.05).
In contrast, contractile responses to KCl (125 mM; 170±12 mN mm−3, n=10; 257±21 mN mm−3 in control, n=13, P<0.005) and phenylephrine (maximum response, 30 μm: 169±24 mN mm−3, n=10; 295±19 mN mm−3 in control, n=13, P<0.001) were significantly reduced in magnitude following chronic NOS inhibition. Sensitivity to phenylephrine was not significantly altered.
The effects of chronic NOS inhibition (Nω‐nitro‐L‐arginine methyl ester, L‐NAME, 10 mg kg−1 daily for 3 weeks) were similar to those of acute NOS blockade with respect to the relaxant responses to SNP and acetylcholine, and also the contraction in response to protein kinase C activation.
Chronic inhibition of NOS significantly increased medial cross sectional area of mesenteric resistance arteries (0.013±0.002 mm2, n=7; 0.009±0.0005 mm2 control, n=15, P<0.05).
Thus, in contrast to the acute effects of NOS inhibition, chronic NOS inhibition results in a down‐regulation of the contractile responses to KCl and phenylephrine in mesenteric resistance arteries, despite an increase in medial cross sectional area. However protein kinase C‐dependent contraction remains relatively enhanced. Endothelium‐dependent relaxation is reduced and endothelium‐independent relaxation is enhanced in a manner similar to the effects of acute NOS blockade.
Cardiotoxicity of emetine dihydrochloride by calcium channel blockade in isolated preparations and ventricular myocytes of guinea‐pig hearts
Authors: Lemmens‐Gruber R. , Karkhaneh A. , Studenik C. , Heistracher P. 
Published: July 2012

The cardiotoxic effects of emetine dihydrochloride on mechanical and electrical activity were studied in isolated preparations (papillary muscles, sinoatrial and atrioventricular nodes, ventricular myocytes) of the guinea‐pig heart.
Force of contraction was measured isometrically, action potentials and maximum rate of rise of the action potential were recorded by means of the intracellular microelectrode technique. Single channel L‐type calcium current (Ba2+ ions as charge carrier) was studied with the patch‐clamp technique in the cell‐attached mode.
Emetine dihydrochloride (8–256 μm) reduced force of contraction in papillary muscles and spontaneous activity of sinoatrial and atrioventricular nodes concentration‐dependently; the negative inotropic effect was abolished when the extracellular Ca2+ concentration was increased.
Maximum diastolic potential, action potential amplitude, maximum rate of rise of the action potential and the slope of the slow diastolic depolarization were decreased by emetine in sinoatrial as well as atrioventricular nodes, while action potential duration was prolonged in both preparations (1–64 μm).
The amplitude of the L‐type calcium single channel current was not altered by emetine dihydrochloride, while average open state probability was decreased concentration‐dependently (10, 30 and 60 μm).
The most prominent effect of emetine dihydrochloride on single channel current was an increase of sweeps without activity.
At 60 μm, emetine dihydrochloride caused a decrease of the mean open time and an increase of the mean closed time. The number of openings per record and number of bursts per record were reduced.
It is concluded that emetine dihydrochloride produces an L‐type calcium channel block which might contribute to its cardiac side effects.
Binding and competitive inhibition of amine uptake at postsynaptic neurones (transport‐P) by tricyclic antidepressants
Authors: Al‐Damluji S. , Kopin I.J. 
Published: July 2012

We have provided evidence for a novel amine uptake process for which prazosin is a substrate in postsynaptic neurones, characterized by a paradoxical increase in accumulation of the radioligand when the concentration of the unlabelled drug is increased above 10−7 m. This increase is due to activation of a proton‐dependent, vacuolar type‐ATPase‐linked uptake process which is blocked by desipramine but is resistant to reserpine. We have now examined the effects of tricyclic antidepressants on this uptake system in a cell line derived from hypothalamic peptidergic neurones, known to be innervated by noradrenergic nerve terminals in vivo.
[3H]‐imipramine bound to the cells and was displaced by unlabelled imipramine, desipramine, amitriptyline and nortriptyline. The data fitted a single binding site model. This is the first demonstration of antidepressant binding sites in postsynaptic neurones.
There was no increase in the binding of [3H]‐imipramine at high concentrations of unlabelled imipramine, suggesting that antidepressants inhibit uptake but are not themselves accumulated by peptidergic gonadotrophin releasing hormone neurones.
Accumulation of prazosin was competitively inhibited by antidepressants. Tertiary amines were slightly more potent than secondary amines and the presence of a nitrogen atom in the heterocyclic ring enhanced blocking activity.
The affinities of the antidepressants for the uptake process are within the range of plasma concentrations that are observed during therapeutic use of these compounds. Since it is likely that this uptake process has a physiological function, its inhibition by antidepressants may provide a new avenue for investigating the mechanism of action of these compounds.
Effects of a selective adenosine A1 receptor antagonist on the development of cyclosporin nephrotoxicity
Authors: Balakrishnan V.S. , von Ruhland C.J. , Griffiths D.F.R. , Coles G.A. , Williams J.D. 
Published: July 2012

The clinical application of cyclosporin as an immunosuppressive agent is limited by its nephrotoxicity.
The effect of FK453, a selective A1‐receptor antagonist, administered twice daily to rats at a dose of 100 mg kg−1 was assessed on the development of nephrotoxicity induced by cyclosporin (10 mg kg−1 i.p. daily) administered for 14 days. The effects of nifedipine administered twice daily (0.3 mg kg−1 s.c.) for 14 days, on cyclosporin nephrotoxicity were also studied.
Cyclosporin induced a 46.58% and 35.78% decline in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) respectively and a reduction of 16.69% in filtration fraction (FF). Co‐administration of FK453 resulted in falls of 30.5%, 18.59% and 14.7% in GFR, ERPF and FF respectively, the former two significantly less than the falls seen with cyclosporin (CyA) alone (P < 0.05 vs CyA, ANOVA).
Nifedipine appeared to have a more pronounced protective effect resulting in a decline of only 20.91% in GFR, with no significant change in ERPF (increase of 0.93%) when co‐administered with CyA.
These observations indicate adenosine plays a minor role in the pathophysiology of CyA nephrotoxicity.
Role of nitric oxide in the induction and expression of morphine tolerance and dependence in mice
Authors: Dambisya Yoswa M. , Lee Tat‐Leang 
Published: July 2012

The possible involvement of nitric oxide (NO) in the induction and expression of morphine tolerance and dependence was studied in mice. A two‐day repeated injection regimen was used to induce morphine tolerance and dependence. Tolerance was assessed by the tail flick test and physical dependence by naloxone challenge, on the third day.
Two days pretreatment with L‐arginine (20 mg kg−1, twice daily) or D‐NG‐nitro arginine methyl ester (D‐NAME, 20 mg kg−1, twice daily) alone had no effect on subsequent morphine antinociception. L‐NG‐monomethyl arginine (L‐NMMA, 10 mg kg−1, twice daily) for two days led to a slight increase (not statistically significant) in morphine antinociception; while L‐NG‐nitro arginine methyl ester (L‐NAME, 10 mg kg−1, twice daily) for two days led to attenuation of morphine analgesia. None of the animals treated with these drugs alone showed signs characteristic of the opioid withdrawal syndrome upon naloxone challenge.
Induction phase L‐arginine slowed the development of opioid tolerance and physical dependence, while L‐NAME and L‐NMMA led to a higher degree of tolerance but had no effect on the development of physical dependence.
L‐Arginine and D‐NAME had no effect on the expression of morphine tolerance and physical dependence. Expression phase L‐NAME and L‐NMMA, on the other hand, attenuated morphine tolerance and reduced the incidence of withdrawal signs.
NO may, therefore, play a role in both phases of morphine tolerance and dependence: elevation of NO levels during the induction phase delays the development of opioid tolerance/dependence, while inhibition of NO synthase accelerates the development of tolerance. Inhibition of NO attenuates the expression of both tolerance and physical dependence.
Potentiation by cadmium ion of ATP‐evoked dopamine release in rat phaeochromocytoma cells
Authors: Ikeda Makoto , Koizumi Schuichi , Nakazawa Ken , Inoue Kaori , Ito Kanako , Inoue Kazuhide 
Published: July 2012

The effects of cadmium ion (Cd2+) on release of dopamine and on an inward current evoked by extracellular ATP were investigated in rat phaeochromocytoma PC12 cells.
Cd2+ (100 μm‐3 mM) potentiated the dopamine release evoked by 30 μm ATP from the cells. Cd2+ (100 μm) shifted the concentration‐response curve of ATP‐evoked dopamine release to the left without affecting the maximal response.
Suramin (30 μm) completely abolished the dopamine release evoked by 30 μm ATP but only partially inhibited the release evoked by 100 μm ATP consistent with its role as a competitive antagonist. The response evoked by 30 μm ATP in the presence of Cd2+ (300 μm) was comparable to that observed with 100 μm ATP alone; however, only the former was almost completely inhibited by suramin.
Cd2+ (100 μm) potentiated an inward current activated by 30 μm ATP alone. A higher concentration of Cd2+ (300 μm) had a smaller effect on amplitude potentiation but significantly prolonged the duration of the current.
The time‐course of the ATP‐evoked dopamine release was investigated using a real‐time monitoring system for dopamine release. Although Cd2+ (300 μm) had little effect on the time‐course of activation the ATP‐evoked dopamine release, it produced a long‐lasting dopamine release which slowly returned to the baseline.
Taken together, these observations suggest that Cd2+ enhances ATP‐evoked dopamine release by affecting P2‐purinoceptor/channels. The enhancement may be attributed to a Cd2+‐dependent increase in sensitivity to ATP.
Micturition in conscious rats with and without bladder outlet obstruction: role of spinal α1‐adrenoceptors
Authors: Ishizuka Osamu , Persson Katarina , Mattiasson Anders , Naylor Alasdair , Wyllie Michael , Andersson Karl‐Erik 
Published: July 2012

In normal rats and rats with bladder hypertrophy secondary to outflow obstruction, undergoing continuous cystometry, we examined the responses to the selective α1‐adrenoceptor antagonist doxazosin given intrathecally (i.t.) and intra‐arterially (i.a.). In addition, we investigated the effects of the drug on L‐dopa‐induced bladder hyperactivity in normal, unobstructed rats.
Doxazosin 50 nmol (approximately 60 μg kg−1), given i.t., decreased micturition pressure in normal rats and in animals with post‐obstruction bladder hypertrophy. The effect was much more pronounced in the animals with hypertrophied/overactive bladders. Doxazosin did not markedly affect the frequency or amplitude of the unstable contractions observed in obstructed rats. In contrast, however, doxazosin reduced L‐dopa‐induced bladder overactivity. When tested, the enantiomers of doxazosin produced qualitatively similar effects to doxazosin, but there was no evidence of stereoselectivity.
The results suggest that in addition to the well documented action on prostatic and lower urinary tract smooth muscle, and an effect on the sympathetic outflow to the bladder, bladder neck, prostate, and external urethral sphincter, doxazosin may have an action at the level of the spinal cord and ganglia, thereby reducing activity in the parasympathetic nerves to the bladder. This effect is more pronounced in rats with bladder hypertrophy than in normal rats.
Blockade of swelling‐induced chloride channels by phenol derivatives
Authors: Gschwentner Martin , Jungwirth Andreas , Hofer Sabine , Wöll Ewald , Ritter Markus , Susanna Alex , Schmarda Andreas , Reibnegger Gilbert , Pinggera Germar M. , Leitinger Markus , Frick Julian , Deetjen Peter , Paulmichl Markus 
Published: July 2012

. In NIH3T3 fibroblasts, the chloride channel involved in regulatory volume decrease (RVD) was identified as ICln, a protein isolated from a cDNA library derived from Madin Darby canine kidney (MDCK) cells. ICln expressed in Xenopus laevis oocytes gives rise to an outwardly rectifying chloride current, sensitive to the extracellular addition of nucleotides and the known chloride channel blockers, DIDS (4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonic acid) and NPPB (5‐nitro‐2‐(3‐phenylpropylamino)‐benzoic acid). We set out to study whether substances structurally similar to NPPB are able to interfere with RVD.
. RVD in NIH3T3 fibroblasts and MDCK cells is temperature‐dependent.
. RVD, the swelling‐dependent chloride current and the depolarization seen after reducing extracellular osmolarity can be blocked by gossypol and NDGA (nordihydroguaiaretic acid), both structurally related to NPPB.
. The cyclic AMP‐dependent chloride current elicited in CaCo cells is less sensitive to the two substances tested while the calcium‐activated chloride current in fibroblasts is insensitive.
. The binding site for the two phenol derivatives onto ICln seems to be distinct but closely related to the nucleotide binding site identified as G × G × G, a glycine repeat located at the predicted outer mouth of the Icln channel protein.
Inhibition of NO‐mediated responses by 7‐ethoxyresorufin, a substrate and competitive inhibitor of cytochrome P450
Authors: Li C.G. , Rand M.J. 
Published: July 2012

. The effects of 7‐ethoxyresorufin (7‐ER), which is a substrate for and competitive inhibitor of cytochrome P450, were studied on responses to nitric oxide (NO), the NO donors sodium nitroprusside (SNP) and glyceryl trinitrate (GTN), acetylcholine‐induced endothelium‐dependent relaxations of rat and rabbit aortic rings and nitrergic nerve stimulation‐induced relaxations of rat anococcygeus muscles.
. In rat and rabbit aortic rings, 7‐ER (2 μm) inhibited the relaxations to acetylcholine in endothelium‐intact preparations and the relaxant action of NO in endothelium‐denuded preparations. Relaxant responses to SNP and GTN were inhibited by 7‐ER in the rat but not rabbit aortic rings. However, the relaxant actions of papaverine and 8‐bromo‐cyclic GMP were not affected by 7‐ER.
. In rat anococcygeus muscles, 7‐ER (2 μm) inhibited the relaxant action of NO, but relaxations elicited by nitrergic nerve stimulation were only partly inhibited by a higher concentration of 7‐ER (10 μm).
. After inhibition by 7‐ER, superoxide dismutase (100 u ml−1) restored NO‐induced relaxations of the rat aortic rings, but not acetylcholine‐, SNP or GTN‐induced relaxations, and restored NO‐ and nitrergic nerve stimulation‐induced relaxations of anococcygeus muscles.
. Another cytochrome P450 inhibitor, troleandomycin (10–30 μm), had no effect on NO‐ or acetylcholine‐induced relaxations of rat aortic rings and NO‐ or nitrergic nerve stimulation‐induced relaxations of anococcygeus muscles. However, resorufin, an analogue of 7‐ER, inhibited responses to acetylcholine, NO and GTN in rat aortic rings.
. The results suggest that 7‐ER inhibited responses to NO and nitrergic nerve stimulation through generation of superoxide radicals. However, an additional mechanism may be involved in the reduction in acetylcholine‐induced responses in aortic rings.
. A 7‐ER sensitive P450 system may be involved in the bioactivation of GTN and SNP in rat aortic rings, but not in rabbit aorta or rat anococcygeus muscles.