bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of phosphatidylserine on the decreased cardiovascular response to clonidine microinfused into the nucleus tractus solitarii of old rats
Authors: Mollace V. , Masuda Y. , Pelaggi T. , Nisticò G. 
Published: July 2012

The cardiovascular effects of direct microinfusions of clonidine into the nucleus tractus solitarii (NTS) in rats of different ages were studied.
Clonidine microinfused into the NTS produced a dose‐dependent hypotensive and bradycardic response, which was reduced by previous microinfusion of yohimbine but not of propranolol or prazosin.
Unilateral microinfusion of clonidine into the NTS produced a significantly smaller hypotensive and bradycardic response in 16 month old rats than in 3 month old rats, whereas in older animals (24 month old) the same doses of clonidine were ineffective. In 16 month old rats, yohimbine given into the NTS produced a smaller pressor and tachycardic response than in 3 month old rats whereas in 24 month old animals yohimbine, at the same doses, was unable to change blood pressure and heart rate.
Oral administration of phosphatidylserine (50 mg kg−1 day−1 for 30 consecutive days) enhanced the hypotensive and bradycardic response to clonidine microinfused into the NTS in 16 month old rats. The same schedule of treatment with phosphatidylserine did not affect the cardiovascular response to clonidine in young (3 month old) rats and did not restore responsiveness to clonidine in older rats (24 month old).
Methoxamine and phentolamine, given intravenously, produced similar pressor and depressor responses, respectively in 3, 16 and 24 month old rats, suggesting that the decreased sensitivity to clonidine in old rats was not due to peripheral cardiovascular changes.
In conclusion, the present results indicate that, during aging, there is a decreased sensitivity of α2‐adrenoceptors in the brain. Such an alteration can be reversed by chronic treatment with phosphatidylserine during the initial but not the later stages of aging.
Pharmacological evaluation of a guinea‐pig tracheal epithelium‐derived inhibitory factor (EpDIF)
Authors: Fernandes Lynette B. , Goldie Roy G. 
Published: July 2012

An epithelium‐derived inhibitory factor (EpDIF) released by guinea‐pig tracheal epithelium was evaluated in a co‐axial bioassay system consisting of an epithelium‐intact guinea‐pig tracheal tube surrounding endothelium‐denuded rat aortic strip.
Histamine and several muscarinic agonists induced concentration‐dependent relaxation of phenylephrine‐contracted rat aorta via the release of EpDIF. However, several other agonists did not induce the release of EpDIF from guinea‐pig trachea. These included the nicotinic cholinoceptor agonists nicotine (25 μm), 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP) (25 μm), calcium ionophore A23187 (0.5 μm), bradykinin (0.05‐0.5 μm), substance P (5 μm), platelet activating factor (PAF, 1–100 nm), the leukotrienes (LT) LTC4, LTD4 and LTE4 (0.1–10 nm) as well as hyperosmotic stimuli.
Prostaglandin E2 (PGE2) induced concentration‐dependent contraction of endothelium‐denuded rat aortic preparations, indicating that this prostanoid could not be EpDIF. Furthermore, relaxation to histamine and methacholine, mediated via EpDIF, was not significantly altered in the presence of phenidone (50 μm) the cyclo‐oxygenase/lipoxygenase inhibitor with radical scavenging properties or the cytochrome P‐450 inhibitors metyrapone (1 mm) and SKF 525A (25 μm). This suggests that EpDIF is neither a prostanoid nor a cytochrome P‐450 metabolite of arachidonic acid.
The soluble guanylate cyclase inhibitor, methylene blue (50 μm), caused small but significant increases in the potencies of both histamine and methacholine in co‐axial assemblies, indicating that EpDIF did not activate this enzyme and therefore was not NO or a related substance. The β‐adrenoceptor antagonist, (−)−propranolol (1 μm), and the PAF‐receptor antagonist, WEB 2086 (50 μm), also failed to alter significantly EpDIF‐modulated relaxations. These data suggest that EpDIF is neither a stimulant of β‐adrenoceptors nor of PAF receptors.
The present study provides some evidence that this vascular smooth muscle‐sensitive EpDIF may not be related to the putative EpDIF previously hypothesized to modulate directly spasmogen‐induced airway smooth muscle tone.
The role of adenosine in the hyperaemic response of the hepatic artery to portal vein occlusion (the ‘buffer response’)
Authors: Mathie R.T. , Alexander B. 
Published: July 2012

Adenosine has been shown to be responsible for the hyperaemic response of the hepatic artery to portal vein occlusion (the hepatic arterial ‘buffer response’).
The effect of adenosine receptor blockade and of adenosine uptake inhibition on the hepatic arterial response to portal vein occlusion was investigated in three groups of anaesthetized dogs.
Venous return and arterial blood pressure were maintained during periods of portal occlusion by establishing a side‐to‐side portacaval shunt. Hepatic artery and portal vein blood flows were measured with electromagnetic flowmeters.
Hepatic arterial infusions of 8‐phenyltheophylline (500 μg kg−1 min−1) and 3‐isobutyl‐1‐methylxanthine (75 μg kg−1 min−1), doses sufficient to block the vasodilator response of the hepatic artery to exogenously applied adenosine, reduced the magnitude of the ‘buffer response’ by 50% and 75%, respectively.
Intravenous infusion of dipyridamole (100 μg kg−1 min−1), a dose sufficient to potentiate the vasodilator response of the hepatic artery to exogenously applied adenosine, had little effect on the ‘buffer response’.
It is concluded that adenosine is an important, but not the sole, agent responsible for the hepatic arterial ‘buffer response’.
Enhanced α‐adrenoceptor responsiveness and receptor number during global ischaemia in the Langendorff perfused rat heart
Authors: Butterfield Michelle C. , Chess‐Williams Russell 
Published: July 2012

Idioventricular rate responses and adrenoceptor number have been examined in normal Langendorff hearts perfused at 70 cmH2O and in ‘ischaemic’ hearts perfused at 10 cmH2O.
In hearts perfused at normal pressure, ventricular rate responses to phenylephrine in the presence of propranolol were biphasic with low concentrations of phenylephrine reducing, and high concentrations increasing, ventricular rate. Both responses were abolished in the presence of prazosin (100 nm). In hearts perfused at low pressure, the negative chronotropic responses to phenylephrine were no longer present and positive chronotropic responses were enhanced compared with those of control tissues. The number of ventricular [3H]‐prazosin binding sites was also significantly increased during ischaemia.
Idioventricular rate responses to isoprenaline were depressed in ischaemic tissues compared with controls, but [3H]‐dihydroalprenolol binding was not altered in these hearts.
The incidence and duration of arrhythmias which occurred during 30 min of global ischaemia and reperfusion were not significantly altered in the presence of 100 nm prazosin.
These results demonstrate that reducing the perfusion pressure of rat isolated hearts enhances α‐adrenoceptor‐mediated responses and increases α‐adrenoceptor density. Whether the increase in α‐adrenoceptor responsiveness during ischaemia is involved in arrhythmogenesis requires further investigation.
Characterization of cardiac angiotensin converting enzyme (ACE) and in vivo inhibition following oral quinapril to rats
Authors: Fabris Bruno , Yamada Hiroshi , Cubela Rose , Jackson Bruce , Mendelsohn Frederick A.O. , Johnston Colin I. 
Published: July 2012

Angiotensin converting enzyme (ACE) from the rat heart and lung was studied by use of the radioligand [125I]‐351A.
Displacement of the bound radioinhibitor [125I]‐351A was used to assess the relative potency of six ACE inhibitors in rat heart and lung homogenates and estimate the binding association constant (KA).
The KA for atrial preparations was significantly higher than that of the lung (P < 0.025) and also the ventricles (P < 0.005). Ventricular preparations and preparations from the lung also differed significantly (P < 0.05). These differences in KA were noted for all six ACE inhibitors used to displace the radioligand.
The rank order of potency of the ACE inhibitors was quinaprilat = benazeprilat > perindoprilat > 351A > lisinopril > fosinoprilat.
Cardiac ACE inhibition was studied ex vivo following oral administration of quinapril to rats. Following 0.3 mg kg−1 quinapril, the time course and degree of inhibition of ventricular and atrial ACE were similar.
These results suggest that the detected differences in KA noted have only a limited potential biological significance. The difference in KA may reflect variations in the structure or conformation of ACE in different tissues.
Antiarrhythmic properties of tedisamil (KC8857), a putative transient outward K+ current blocker
Authors: Beatch G.N. , Abraham S. , MacLeod B.A. , Yoshida N.R. , Walker M.J.A. 
Published: July 2012

Rats were used to evaluate the antiarrhythmic properties of tedisamil, a novel agent with the electrophysiological properties of a Class III antiarrhythmic drug. Tedisamil was tested against coronary artery occlusion‐induced arrhythmias in conscious animals.
The actions of tedisamil on the ECG, as well as responses to electrical stimulation, were compared with those on the configuration of epicardial intracellular action potentials recorded in vivo.
Tedisamil (1–4 mg kg−1, i.v.) caused bradycardia, elevated blood pressure and dose‐dependently reduced ventricular fibrillation (VF) induced by occlusion of the left anterior descending coronary artery. Other ischaemia‐associated arrhythmias were not so well suppressed. Antiarrhythmic activity was greatest when the tedisamil‐induced bradycardia was prevented by electrically‐pacing the left ventricle.
Tedisamil dose‐dependently lengthened the effective refractory period and prevented electrically‐induced VF. In vivo, tedisamil (0.5–4 mg kg−1, i.v.) prolonged the duration of epicardial intracellular action potentials by up to 400%.
Results showed that tedisamil possessed antifibrillatory actions in rats that were related to Class III electrophysiological actions as revealed by electrical stimulation and electrophysiological analyses.
Differential effects of dopamine agonists upon stimulated limbic and striatal dopamine release: in vivo voltammetric data
Authors: Stamford Jonathan A. , Kruk Zygmunt L. , Millar Julian 
Published: July 2012

Fast cyclic voltammetry at carbon fibre microelectrodes was used in rats anaesthetized with chloral hydrate to monitor dopamine release in the caudate and nucleus accumbens evoked by electrical stimulation of the median forebrain bundle. Stimulation trains (50 Hz sinusoidal current, 100 ± 10 μA r.m.s., 2 s duration) were repeated every 5 min throughout the experiment.
The actions of the dopamine agonists quinpirole, pergolide, SKF 38393, bromocriptine, (+)‐3‐(3‐hydroxyphenyl)‐N‐n‐propylpiperidine ((+)‐3PPP) and (−)‐3PPP were compared in the two nuclei.
Bromocriptine (10 mg kg−1, i.p.) did not affect release in either nucleus while SKF 38393 caused a fleeting decrease in limbic but not striatal dopamine release at a high dose (20 mg kg−1, i.p.).
Quinpirole and pergolide (both 1 mg kg−1, i.p.) decreased stimulated dopamine release in the nucleus accumbens while in the caudate the drugs each caused a transient, though not quite significant, elevation of stimulated dopamine release followed by decrease in release of the same magnitude as that seen in the nucleus accumbens.
The (−)‐enantiomer of 3PPP (20 mg kg−1, i.p.), a partial agonist at the dopamine autoreceptor, increased stimulated dopamine release in both nuclei although the action in the caudate was larger and more prolonged. (+)‐3PPP (20 mg kg−1, i.p.), a full agonist, decreased release in the nucleus accumbens. A small, transient and not significant increase in the caudate was followed by decreased release.
The results are interpreted as being evidence for differences in the dopamine autoreceptor in the two nuclei, possibly in the affinity state of the receptor in each nucleus.
Effects of cyclic nucleotides and phorbol myristate acetate on proliferation of pig aortic endothelial cells
Authors: Moodie Shonna Alexandra , Martin William 
Published: July 2012

The role of cyclic nucleotides and protein kinase C in controlling proliferation of pig aortic endothelial cells (PAEC) in culture was investigated.
Dibutyryl cyclic AMP (30 μm), added twice daily, inhibited proliferation but 8 bromo cyclic GMP (30 μm) had no effect. Two other stimuli known to increase PAEC cyclic GMP content by stimulating particulate and soluble guanylate cyclase respectively, atriopeptin II (10 nm) and sodium nitroprusside (1 μm), were also without effect on proliferation.
Two agents known to inhibit soluble guanylate cyclase and lower intercellular cyclic GMP content, haemoglobin (10 μm) and methylene blue (10 μm), each inhibited proliferation of PAEC.
The inhibitory effect of haemoglobin (10 μm) was mediated by inhibition of soluble guanylate cyclase since it was reversed by agents known to increase cyclic GMP content, i.e. atriopeptin II (10 nm), 8 bromo cyclic GMP (30 μm) or sodium nitroprusside (1 μm). The inhibitory effect of methylene blue (10 μm) was not reversed by these agents.
Phorbol 12‐myristate 13‐acetate (PMA, 0.1 nm–1 μm), which activates protein kinase C, inhibited proliferation in a concentration‐dependent manner. No early stimulation of proliferation was seen wtih PMA. The inactive isomer, 4α‐phorbol 12, 13‐didecanoate (0.3 μm), lacked the ability of PMA to inhibit proliferation of PAEC.
PMA‐induced inhibition of proliferation appeared not to be due to stimulated production of destructive oxygen‐derived free radicals since it was unaffected by the radical scavengers, vitamin E (30 μm) or butylated hydroxytoluene (30 μm). The antiproliferative actions of paraquat (10 μm), an agent which generates free radicals intracellularly, was, in contrast, inhibited by vitamin E or butylated hydroxytoluene. Furthermore, neither dibutyryl cyclic AMP (30 μm) nor 8 bromo cyclic GMP (30 μm) had any effect on the ability of PMA to inhibit proliferation.
This study suggests that cyclic AMP, cyclic GMP and protein kinase C play a role in controlling the proliferation of PAEC.
Probing the molecular dimensions of general anaesthetic target sites in tadpoles (Xenopus laevis) and model systems using cycloalcohols
Authors: Curry S. , Moss G.W.J. , Dickinson R. , Lieb W.R. , Franks N.P. 
Published: July 2012

The series of cycloalcohols C6, C7, C8 and C10 have been used to probe the molecular dimensions of a variety of general anaesthetic target sites.
The general anaesthetic EC50 concentrations of the cycloalcohols were determined for tadpoles (Xenopus laevis). All of the cycloalcohols tested were found to be potent general anaesthetics (on average EC50/Csat = 0.03).
The effects of the cycloalcohols on highly purified luciferase enzymes from fireflies (Photinus pyralis) and bacteria (Vibrio harveyi) were also investigated. Both enzymes were inhibited competitively, with the cycloalcohols competing with firefly luciferin for binding to the firefly enzyme and with n‐decanal for binding to the bacterial enzyme.
The binding site on the firefly enzyme could accommodate two molecules of cycloalcohols C6 and C7 but only a single molecule of the larger cycloalcohols (C8 and C10), implying a volume of the binding site of about 250 cm3 mol−1. In contrast, the binding site on the bacterial luciferase could bind only a single cycloalcohol molecule between C6 and C10.
While all of the cycloalcohols were potent inhibitors of the firefly luciferase enzyme (on average EC50/Csat = 0.015), they were very weak inhibitors of the bacterial luciferase enzyme (on average EC50/Csat = 0.12). Since both enzymes bind long‐chain aliphatic n‐alcohols tightly, the differing affinities of the cycloalcohols for the two enzymes is probably a consequence of geometrical factors.
The cycloalcohols produced very small effects on lipid bilayers. At EC50 concentrations which produce general anaesthesia, lipid bilayer phase transitions were shifted, on average, by only 0.43°C.
We conclude that the general anaesthetic effects of the cycloalcohols can most economically be explained by assuming that the cycloalcohols act at protein binding sites in the central nervous system. These target sites would have binding properties similar to those of the anaesthetic‐binding site on firefly luciferase, but their average volume would be somewhat smaller than 250 cm3 mol−1.
Effects of a novel smooth muscle relaxant, KT‐362, on contraction and cytosolic Ca2+ level in the rat aorta
Authors: Sakata Kiyoshi , Karaki Hideaki 
Published: July 2012

Inhibitory effects of a novel smooth muscle relaxant, KT‐362 (5‐[3‐([2‐(3,4‐dimethoxyphenyl)‐ethyl]amino)‐1‐oxopropyl]‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine fumarate), on contraction and the cytosolic Ca2+ level ([Ca2+]cyt) in isolated vascular smooth muscle of rat aorta were examined.
KT‐362 inhibited the contractions induced by high K+ and noradrenaline. The inhibitory effect was antagonized by an increase in external Ca2+ concentration. A Ca2+ channel activator, Bay K 8644, did not change the effect of KT‐362 on high K+‐induced contraction.
[Ca2+]cyt, measured with fura‐2‐Ca2+ fluorescence, increased during the contractions induced by high K+ or noradrenaline. KT‐362 decreased [Ca2+]cyt and muscle tension stimulated by high K+ or noradrenaline. By contrast, a Ca2+ channel blocker, verapamil, inhibited the noradrenaline‐induced increase in [Ca2+]cyt with only partial inhibition of the noradrenaline‐induced contraction and KT‐362 inhibited the verapamil‐insensitive portion of the contraction without changing [Ca2+]cyt.
In a Ca2+‐free solution, noradrenaline and caffeine induced a transient contraction following a transient increase in [Ca2+]cyt. KT‐362 inhibited the increments due to noradrenaline but not those induced by caffeine.
These results suggest that KT‐362 inhibits vascular smooth muscle contraction by inhibiting Ca2+ channels, receptor‐mediated Ca2+ mobilization, and receptor‐mediated Ca2+ sensitization of contractile elements.
Furosemide inhibits the centrally‐mediated pressor response to clonidine in conscious, normotensive rats
Authors: Kawasaki Hiromu , Nakamura Shigeru , Takasaki Koichiro 
Published: July 2012

The effect of furosemide on the pressor response induced by intracerebroventricular (i.c.v.) injection of clonidine was investigated in freely moving, normotensive rats with chronically implanted arterial catheters.
When injected i.c.v., clonidine at doses of 5 and 10 μg produced a dose‐dependent pressor response and a decrease in heart rate. No depressor response was induced by clonidine.
Systemic (i.v.) pretreatment with furosemide (2–10 mg kg−1) increased urine volume and dose‐dependently inhibited the pressor response to i.c.v. clonidine (10 μg), and a long‐lasting depressor response to clonidine was observed. However, furosemide treatment did not alter the bradycardia produced in response to clonidine.
The systemic treatment with furosemide (10 mg kg−1, i.v.) had no effect on the pressor response to i.v. noradrenaline.
These results suggest that reduction of body fluid volume inhibits the centrally‐mediated pressor response to clonidine and leads to the hypotensive effect. We also suggest that combined treatment with a diuretic increases the hypotensive efficacy of clonidine.
Salmeterol: a potent and long‐acting inhibitor of inflammatory mediator release from human lung
Authors: Butchers P.R. , Vardey C.J. , Johnson M. 
Published: July 2012

The effects of salmeterol, a novel long‐acting β2‐adrenoceptor agonist, have been investigated on antigen‐induced mediator release from passively sensitized fragments of human lung in vitro.
Salmeterol was a potent inhibitor of the release of histamine (–log IC50 = 8.54), leukotriene C4 (LTC4)/LTD4 (–log IC50 = 9.07) and prostaglandin D2 (–log IC50 = 8.81). It was slightly less potent (1–3 fold) than isoprenaline, but significantly more potent (10–35 fold) than salbutamol.
Propranolol competitively antagonized the inhibitory effects of salmeterol on histamine release (pA2 = 8.41) and LTC4/LTD4 release, (pA2 = 8.40) indicating an action via β‐adrenoceptors.
The inhibitory effects of isoprenaline (20 nm) and salbutamol (200 nm) were removed after washing the lung tissue for 2 h and 4 h respectively. In contrast, the inhibitory effects of salmeterol (40 nm) were much longer‐lasting, and were still evident after 20 h.
Salmeterol therefore exhibits potent and persistent inhibition of anaphylactic mediator release from human lung. This anti‐inflammatory effect may be important for the therapeutic potential of salmeterol in the treatment of bronchial asthma.
Effects of NG‐nitro‐l‐arginine methyl ester on vasodilator responses to adrenaline or BRL 38227 in conscious rats
Authors: Gardiner S.M. , Kemp P.A. , Bennett T. 
Published: July 2012

Conscious, Long Evans rats, chronically instrumented for the measurement of regional haemodynamics, were used to assess responses to 3 min infusions of the potassium channel opener, BRL 38227 (1 and 10 μg kg−1 min−1) or adrenaline (0.05 and 0.5 μg kg−1 min−1) in the absence and in the presence of NG‐nitro‐l‐arginine methyl ester (l‐NAME; 3 mg kg−1 h−1), an inhibitor of nitric oxide biosynthesis.
In the absence of l‐NAME, the low dose of BRL 38227 caused slight hypotension and tachycardia, accompanied by small increases in mesenteric and hindquarters blood flow only. However, there were increases in renal, mesenteric and hindquarters vascular conductances. l‐NAME had no effect on any of these responses.
The high dose of BRL 38227 caused substantial hypotension and tachycardia. Renal and hindquarters flows did not change significantly, but there was a marked increase in mesenteric flow. There were only modest increases in renal and hindquarters vascular conductances but a substantial mesenteric vasodilatation. In the presence of l‐NAME, there was a slight reduction of the latter but no other changes in the responses to BRL 38227.
In the absence of l‐NAME, the low dose of adrenaline caused slight hypotension but a marked tachycardia. There were no changes in renal or mesenteric blood flow but a clear‐cut increase in hindquarters flow. Renal and mesenteric vascular conductances showed only small rises, in contrast to the substantial hindquarters vasodilatation. In the presence of l‐NAME, there was significant attenuation of the tachycardia and of the increases in hindquarters flow and vascular conductance in response to adrenaline.
The high dose of adrenaline caused marked hypotension and tachycardia. Renal flow did not change, but there was a fall in mesenteric and a marked rise in hindquarters flow. Renal vascular conductance showed a slight increase but mesenteric vascular conductance did not change significantly, whereas there was a substantial hindquarters vasodilatation. In the presence of l‐NAME, adrenaline caused an increase in blood pressure but no significant change in heart rate; the renal vasodilatation was abolished, there was a mesenteric vasoconstriction, and the hindquarters vasodilatation was markedly reduced. l‐NAME also attenuated the tachycardia induced by adrenaline in animals with no cardiac baroreflexes.
The present results indicate that l‐NAME‐sensitive mechanisms are involved in the vasodilator and tachycardic effects of adrenaline. The relative lack of effect of l‐NAME on responses to BRL 38227 indicates that the changes in the responses to adrenaline were not non‐specific or due to changes in haemodynamic status caused by l‐NAME. The results raise the possibility that the ‘hypertensinogenic’ properties of endogenous adrenaline could be amplified when nitric oxide biosynthesis is impaired.