bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF CALCIUM ENTRY BLOCKERS ON BLOOD PRESSURE AND HEART RATE IN NEUROGENIC HYPERTENSIVE DOGS
Authors: MONTASTRUC P. , VALET P. , DANG TRAN L. , GAILLARD G. , MONTASTRUC J.L. 
Published: August 2009

Summary—The hypotensive and negative chronotropic effects of 5 calcium entry blockers (verapamil 200 μg/kg IV; diltiazem 300 μg/kg IV; nifedipine 5 μg/kg IV; nicardipine 50 μg/kg IV; and bepridil 5 mg/kg IV) were compared in control normotensive and acute neurogenic hypertensive anaesthetized dogs. Acute neurogenic hypertension was induced by sino‐aortic denervation (SAD).In control normotensive dogs, all drugs (except bepridil) induced a slight and transient decrease in blood pressure. Nifedipine and nicardipine increased heart rate whereas the three other drugs remained ineffective.SAD caused a 2–2.5‐fold increase in the hypotensive properties of the 5 drugs in dogs. Moreover, the duration of this induced hypotension was longer than in control normotensive animals. In SAD dogs, all calcium entry blockers significantly decreased heart rate.This study indicates that the direct cardiac inhibitory action of calcium channel blockers is modulated by baroreceptor activity in intact animals. The mechanism of the selective action of calcium entry blockers in hypertensive SAD in contrast to normotensive dogs is discussed.
EFFECTS OF PROPRANOLOL AND SWIM‐TRAINING ON BLOOD PRESSURE, PLASMA ELECTROLYTES, AND VASOPRESSIN IN SPONTANEOUSLY HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: GHAEMMAGHAMI F. , GAUQUELIN G. , GEELEN G. , IBANEZ J. , BOUZEGHRANE F. , CHERBAL F. , MEUNIER C. , GHARIB C. 
Published: August 2009

Summary—The aim of this work was to study the influence of beta‐adrenoreceptor blockade on the adaptation to exercise of one of the hormonal systems (arginine vasopressin) involved in the regulation of blood volume and pressure in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) was measured in SHR and WKY rats during 11 wk of swim training. At the end of the training program we determined post‐exercise values of plasma arginine‐vasopressin (pAVP), osmolality (pOsm), K+ (pK+), Na+ (pNa+), hemoglobin (Hgb), and hematocrit (Hct) in SHR and WKY rats. The following groups were studied: control (C), propranolol treated (PC), swim trained (S), and propranolol‐treated and swim‐trained (PS). SBP was significantly reduced by swim training or propranolol, bu these beneficial effects on SBP were attenuated when propranolol and swim training were combined. pNa+ and pOsm were significantly reduced by training alone in SHR. This reduction of pNa+ and, consequently, of pOsmol without any modification of other parameters could suggest an Na+ loss. In contrast, the SHR group treated with propranolol alone showed a significant reduction in Hct, suggesting an increased plasma volume without Na+ loss.PS SHR showed a significant reduction of Hgb, Hct, proteins, pNa+, and pOsmol, probably as a consequence of the additive effects of swimming‐ and propranolol‐induced hypervolemia with Na+ loss. The slight and nonsignificant reduction in pAVP observed with either training or propranolol treatment alone became much more pronounced and statistically significant when the 2 treatments were combined. WKY rats showed a much smaller response to exercise and beta‐adrenoreceptor blockade than SHR.We conclude that the hypervolemia suggested in PS SHR could be a possible cause of attenuation of the beneficial effects of either swimming or propranolol on SBP.
EFFECTS OF PURINES AND FORSKOLIN ON HAEMOLYSIS
Authors: GONÇALVES M.L. , RIBEIRO J.A. 
Published: August 2009

Summary—Effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine on the antihaemolytic action of procaine, and the effect of ATP on the antihaemolytic actions of lidocaine, dibucaine, tetracaine, pentobarbitone, and chlorpromazine were investigated in rat erythrocytes. The effects of adenosine and its analogues d‐N6‐phenylisopropyladenosine (d‐PIA), l‐N6‐phenylisopropyladenosine (l‐PIA),N6‐cyclohexyladenosine (CHA), 2‐chloroadenosine, andN6‐methyladenosine, as well as the effects of cyclic‐AMP (cAMP), dibutyryl cAMP, and forskolin on haemolysis were also investigated in rat erythrocytes. ATP, ADP, and AMP, but not adenosine, antagonized in a concentration‐dependent manner the antihaemolytic action of procaine, and ATP was ineffective against the antihaemolytic actions of lidocaine, dibucaine, tetracaine, pentobarbitone, and chlorpromazine. Adenosine and its analogues, but notN6‐methyladenosine, protected erythrocytes against hypotonic haemolysis in a concentration‐dependent manner. The order of potencies was: d‐PIA>CHA> l‐PIA>adenosine>2‐chloroadenosine. The effect of adenosine on haemolysis was not prevented by theophylline, 8‐phenyltheophylline, or 8‐sulfophenyltheophylline. Dibutyryl cAMP, a stable analogue of cAMP, and forskolin, a specific activator of adenylate cyclase, mimicked the antihaemolytic action of adenosine. cAMP was less efficient than adenosine.Adenine nucleotides antagonized the antihaemolytic action of procaine, probably due to calcium‐chelating properties. In contrast, adenine nucleosides have antihaemolytic properties. The possibility that the antihaemolytic effects of these substances relate to cAMP and/or to lipophilicity is discussed.
ANTIHYPERTENSIVE DRUGS AND BARORECEPTOR REFLEX CONTROL OF HEART RATE AND BLOOD PRESSURE
Authors: BERDEAUX A. , GIUDICELLI J.F. 
Published: August 2009

Summary—The arterial baroreceptor reflex (BR; aortic and carotid sinus BR) and the cardiopulmonary BR are the most important reflexes acting as buffer systems for the maintenance of arterial pressure around a fixed physiologic value. They act as permanent inhibitory systems on the central cardiovascular structures and they can be either activated or deactivated by using selective techniques. During chronic hypertension there are structural alterations of the peripheral and/or central components of the BR that become «reset», with a shift in the function curve relating BR activity to blood pressure (BP) in the direction of higher pressure values. As a consequence of the hypertension‐induced resetting phenomenon, both the threshold pressure and sensitivity of BR are disturbed. However, if BR resetting during hypertension clearly decreases the sensitivity of BR control of heart rate (HR), BR control of peripheral resistance and arterial pressure as a whole is preserved and even increased when hypertension develops. Thus, this apparent discrepancy between BR control of HR and BP during hypertension demonstrates that evaluation of an antihypertensive therapy on reflex control of HR alone cannot predict what will happen to BR control of the whole cardiovascular system. Regarding BR control of HR, in contrast to the classical arteriolar vasodilators such as hydralazine and its derivatives, the majority of the modern antihypertensive drugs do not evoke reflex tachycardia in response to lowering of BP in normotensive or hypertensive subjects. Although the intrinsic pharmacologic mechanisms of action of these drugs on BR may be quite different (e.g., α1,‐or β‐adrenoreceptor blocking agents, converting enzyme inhibitors, certain calcium‐channel blockers of the phenyldihydropyridine group, and so on), they all shift in a parallel manner the set‐point of the BR response curve towards lower pressures, with no change in HR or R‐R interval. Generally, this resetting phenomenon occurs after several weeks or months of antihypertensive therapy, but it can also occur acutely (e.g.after IV injection) after administration of drugs such as prazosin or ketanserin. Finally, antihypertensive agents such as clonidine and methyldopa can simultaneously reset the BR and increase its sensitivity, thus leading to almost complete restoration of control of HR response despite the concomitant decrease in BP.Regarding BR control of blood pressure, only captopril and especially celiprolol (a β1‐adrenoreceptor blocking drug with vasodilating properties) are able to restore almost normal BR control of arterial pressure.
ELECTROPHYSIOLOGICAL ANALYSIS OF THE ACTION OF NIFEDIPINE AND NICARDIPINE ON MYOCARDIAL FIBERS
Authors: CHARNET P. , OUADID H. , RICHARD S. , NARGEOT J. 
Published: August 2009

Summary—The effects of nifedipine and nicardipine, 2 dihydropyridines (DHP) used in the treatment of cardiovascular disorders, were compared in frog atrial fibers. Rapid photolysis of nifedipine with a single UV flash (1‐ms duration) reversed the block, allowing comparison of effects of both drugs on the same preparation, and manipulation of the calcium channel on a millisecond timescale. The results show that inhibition of the action potential (AP) and slow inward current (Isi) is more pronounced with nifedipine than with nicardipine. Concentration‐effect relationships confirm that nicardipine (IC50= 1 μM) is less potent than nifedipine (IC50= 0.2 μM) in blocking cardiac calcium channels. Both DHP block calcium channels in the closed state at the resting potential, inducing a large tonic block (in the absence of stimulation). An additional phasic block can be observed with nifedipine and nicardipine. A slight voltage dependence to the block is observed for both DHP, their effects being enhanced at depolarized holding potentials. Rapid unblocking of calcium channels by a single light flash, presented during the decay phase of Isi, reveals a higher affinity of DHP for inactivated channels. This effect is most pronounced when inactivation is slowed by using Ba+ +, Sr+ +, or Na+ ions as the current carriers. Open channel block is also suggested. The mechanism of DHP action on calcium channels can be described according to the «modulated receptor hypothesis». These DHP exhibit an additional nonspecific effect on potassium channels.It is concluded that nicardipine is a less potent Ca+ +antagonist than nifedipine in atrial fibers and that the reduction of delayed potassium current, which occurs in a similar range of concentrations to the blockade of Isi, could also be involved in its therapeutic effects.
INHIBITION OF THE COLONIC MOTOR RESPONSE TO EATING BY PINAVERIUM BROMIDE IN IRRITABLE BOWEL SYNDROME PATIENTS
Authors: FIORAMONTI J. , FREXINOS J. , STAUMONT G. , BUENO L. 
Published: August 2009

Summary— The effect of pinaverium bromide on the colonic motor response to eating was investigated in 10 irritable bowel syndrome patients, by means of an intraluminal probe supporting 8 groups of electrodes. At each site examined from transverse to sigmoid colon, the electromyograms exhibited 2 kinds of spike bursts: short spike bursts (SSB) localized at one electrode, and long spike bursts (LSB), isolated, propagated orally or aborally over a few centimeters, or aborally propagated over the whole length of the colon investigated (migrating long spike bursts, MLSB). Recordings were continously performed over 24 hr. Each patient received at 7.00 p.m. on day 1 and at noon on day 2 an 800–1000 Kcal meal preceded by IV administration of pinaverium bromide (4 mg) or placebo.After placebo administration, the duration of LSB activity and the number of MLSB were significantly increased over 3 postprandial hr by comparison with the 2 hr preceding the meal. After pinaverium injection no significant postprandial change in LSB and MLSB activity was noted. The SSB activity was not modified after the meals preceded by placebo or pinaverium injection.These results suggest that the inhibitory action of pinaverium bromide on postprandial colonic motility may support the clinical efficacy of this agent in the treatment of the irritable bowel syndrome.
PHARMACOKINETIC INTERACTION BETWEEN NIFEDIPINE AND PROPRANOLOL
Authors: ZYLBER‐KATZ E. , TURETZ‐ABRAMOVITCH M. , KOREN G. , LEVY M. 
Published: August 2009

Summary— In 8 healthy volunteers, single‐dose nifedipine pharmacokinetics were compared with and without the coadministration of propranolol.An elevation of the mean Cmax was found, from 73.9±14.1 when nifedipine was taken alone, to 115.7±12.1 (SE) ng/ml (P<0.02) when the agent was combined with propranolol. The AUC0‐∞ increased as well, from 287.1±33.5 to 363.0±54.3 (SE) (μg.hr)/1 (P<0.01), indicating an increase in bioavailability. Propranolol treatment did not significantly affect the nifedipine half‐life (α or β phase) or the estimated volume of distribution, whereas systemic clearance tended to decrease in 6 of the subjects.The most likely explanation for increased bioavailability of nifedipine when coadministered with propranolol is by a reduction of the hepatic ± first‐pass ± clearance, as a result of changes in hepatic blood flow.
A NEW ENDOGENOUS ANXIOLYTIC AGENT: l‐PYROGLUTAMIC ACID
Authors: BENI M. , PELLEGRINI‐GIAMPIETRO D.E. , MORONI F. 
Published: August 2009

Summary—By use of a simple anticonflict procedure (Vogel test), it was demonstrated that l‐pyroglutamic acid (l‐pyrrolidone carboxylic acid [l‐PCA]), an amino acid naturally occurring in mammalian tissues and fluids, possesses anxiolytic activity. This effect was stereospecific (d‐PCA was inactive) and, in the rat, it was not associated with a decrease in motor activity. Ro 15–1788, a benzodiazepine antagonist, did not modify l‐PCA actions. Furthermore, anxiolytic doses of the amino acid did not change the content of 5‐hydroxytryptamine (5‐HT) or of 5‐hydroxyindoleacetic acid (5‐HIAA) in the rat cortex and hippocampus.These results suggest that the mechanism of the anxiolytic activity of l‐PCA is different from that of the benzodiazepines and of 5‐HT1aagonists.
BLOOD BINDING AND TISSUE UPTAKE OF DRUGS. RECENT ADVANCES AND PERSPECTIVES
Authors: TILLEMENT J.‐P. , URIEN S. , CHAUMET‐RIFFAUD P. , RIANT P. , BREE F. , MORIN D. , ALBENGRES E. , BARRE J. 
Published: August 2009

Summary—The free drug hypothesis, which states that only the unbound moiety of drug in blood is available for tissue diffusion, is discussed according to recent investigations. In some experimental conditions, it must be assumed that part of the protein‐bound drug in plasma is extracted during a single passage through the organ studied. The mechanisms underlying these observations are not unequivocal and remain hypothetical. In the liver, high‐affinity binding sites for serum albumin have been demonstrated, and they would explain the high extraction by liver of endogenous and exogenous compounds.However, these experiments measure the unidirectional transfer of a drug from the vascular to the extravascular space in non‐steady‐state conditions. Hence, in steady‐state conditions, the free drug hypothesis cannot be ruled out because it is supported by numerous pharmacokinetic studies.
BETA‐BLOCKING ACTIONS OF BETAXOLOL ON THE ISOLATED RAT PORTAL VEIN
Authors: VIDAL‐BERETERVIDE K. 
Published: August 2009

Summary—The characteristics of the β‐adrenoceptor population mediating the actions of noradrenaline and isoproterenol in the rat portal vein were examined in comparison with those in the rat atria.In the portal vein, the pA2values obtained for the selective β1‐adrenoceptor antagonist betaxolol were 100‐fold lower than those obtained in the atria, suggesting that in the rat portal vein a population of β2‐adrenoceptors is highly predominant.
SPONTANEOUS AND OUABAIN‐INDUCED EFLUX OF CATECHOLAMINES AND DIHYDROXYPHENYLGLYCOL IN TWO CANINE BLOOD VESSELS
Authors: BRANCO D. , OSSWALD W. 
Published: August 2009

Summary— The spontaneous efflux of endogenous noradrenaline, dopamine, dihydroxyphenylglycol (DOPEG) from adrenergic nerve endings of 2 canine blood vessels (the mesenteric artery and the saphenous vein) were studied during 8 successive incubation periods of 15 min each. Extraneuronal uptake and 0‐methylation were minimized by the presence of adequate concentrations of tropolone and hydrocortisone.Both vessels had an efflux characterized by a decline in the 3 catechols, which was most marked for noradrenaline; the mesenteric artery lost larger amounts than the saphenous vein. Ouabain caused a large increase in the efflux of noradrenaline and dopamine and a reduction of DOPEG efflux. Cocaine had only a modest effect, more evident in the case of the mesenteric artery, increasing noradrenaline and reducing DOPEG effluxes. The combination of ouabain and cocaine had no additive effects, and the effects of ouabain were even reduced (on some parameters) by cocaine.Accordingly, the noradrenaline: DOPEG ratio was markedly increased by ouabain, but not by cocaine; cocaine significantly reduced the effects of ouabain. The ratio dopamine: noradrenaline was decreased by cocaine and by ouabain. Comparison of tissue content and efflux allowed us to conclude that apparently no significant de novo synthesis of noradrenaline occurred during the incubation period.We conclude that a fast and early component of spontaneous efflux is due to loss from the neurons and that its greater magnitude in the mesenteric artery may be due to differences in neuronal [Na+] and/or to differences in neuronal membrane adenosine triphosphatase activity. The results also suggest that neuronal reuptake plays only a minor role in the handling of spontaneously released noradrenaline.
NEUROTRANSMITTERS AND INTRAOCULAR PRESSURE
Authors: LAPALUS P. , ELENA P.P. 
Published: August 2009

Summary— The role of the ocular autonomic nervous system in IOP regulation has been well established. Pharmacological and autohistoradiographic studies confirmed the high density of beta2 and alpha2 receptors on ciliary processes and iris epithelium. Their respective pharmacological activation or blockade is discussed. The role of other ocular neurotransmitters is also complex, as shown by the paradoxical similar action of dopamine agonists and antagonists on IOP.Concerning the cholinergic system, ocular muscarinic receptors are pharmacologically not well documented. Numerous other neurotransmitters may modulate IOP without necessarily leading to the development of new drugs. Drugs of the future will probably concentrate on dopaminergic agonists, cAMP‐stimulators such as forskolin, prostaglandins, and cannabinoids.
COMPARATIVE EFFECTS OF ACEBUTOLOL AND LABETALOL ON PERIPHERAL HEMODYNAMICS IN HEALTHY VOLUNTEERS
Authors: WURM M. , KANTELIP J.P. , DUCHENE‐MARULLAZ P. 
Published: August 2009

Summary—During a 28‐day treatment period, 10 healthy volunteers in a cross‐over, double‐blind study received at random 200 mg of either acebutolol or labetalol twice a day. Each treatment period was followed by administration of a placebo over an equal length of time.Only acebutolol reduced heart rate measured in the supine position significantly at rest, whereas acebutolol and labetalol reduced it significantly after exercise on the treadmill.Only acebutolol lowered humeral pressure at rest but not after exercise. Neither drug produced a change in blood pressure in the ankle or in the first toe at rest or after exercise.Blood flow measured by plethysmography was increased by labetalol in the calf by comparison with placebo and in the first toe by comparison with placebo and acebutolol.Labetalol lowered peripheral resistance significantly in comparison with placebo in the calf and first toe. Acebutolol tended to lower the resistance insignificantly in the calf but to increase resistance in the first toe.
ALGEBRAIC POTENTIAL OF THE HILL EQUATION AS AN ALTERNATIVE TOOL FOR PLOTTING DOSE (OR TIME)/EFFECTS RELATIONSHIPS IN TOXICOLOGY: A THEORETICAL STUDY
Authors: BOUNIAS M. 
Published: August 2009

Summary— Use of the Hill equation in plotting the results of toxicological experiments offers the following advantages:

In dose/effect relationships, the maximum response RM can be accurately determined by means of a described new noniterative algebraic method, from both hyperbolic and sigmoidal responses expressed in natural (nontransformed) units. The Hill coefficient (n) and the dose giving 50% (f50) or X% (fx) of RM, as well as their SD, are accurately deduced.
In time‐course experiments with sigmoidal shape, an additional set of parameters, readily available from the former basic 3, makes it possible to avoid arbitrary choices, such as the time at which a percentage or mortality is considered. The slopes of the tangents at the inflexion point (maximum rate of response) and at half‐maximum effect, then the coordinates of these points and the horizontal intercept of the tangent at inflexion point (as an index of initial lag‐phase) will give increasing and decreasing functions of doses, respectively, depending on RM, f50, and (n).
The processes described first allow the classical parameters LD50 (or LDx) and LT50 (or LTx: X%‐lethality time) to be calculated with high algebraic accuracy, in addition to RM and (n), both of which are of great interest in the general case of ligand‐receptor interactions. Thus, the deduced set of additional indexes, not readily available from classical “Probits‐type” transformations, eliminates the mortgage of subjective operations.
SK&F 89124, A POTENT AND SELECTIVE AGONIST AT PREJUNCTIONAL DOPAMINE RECEPTORS
Authors: HIEBLE J.P. , SULPIZIO A.C. , SARAU H.M. , FLAIM K.E. , BLUMBERG A.L. , McCAFFERTY J.P. , ZEID R.L. 
Published: August 2009

Summary—SK&F 89124 (4‐[2‐(N,N‐di‐n‐propylamino)ethyl]‐7‐hydroxy‐2(3H) indolone) can be considered as a derivative ofN,N‐di‐n‐propyldopamine (DPDA) in which themeta‐hydroxyl is replaced by a cyclic amide function. SK&F 89124 is at least one order of magnitude more potent than DPDA as an agonist at peripheral inhibitory prejunctional dopamine receptors (DA2receptors) in the isolated perfused rabbit ear artery. A potent agonist action of SK&F 89124 at the DA2receptor can also be demonstrated by inhibition of radioactive overflow from prelabelled canine coronary artery or saphenous vein, and in the anesthetized dog as an inhibition of the tachycardia induced by cardioaccelerator nerve stimulation or the increase in hind‐limb perfusion pressure induced by stimulation of the lumbar sympathetic chain. SK&F 89124 is a potent inhibitor of the binding of [3H]spiroperidol to D2receptors in bovine pituitary homogenates.High concentrations of SK&F 89124 do not activate the adenylate cyclase D1receptor in rat caudate homogenates, nor produce activation of α2‐adrenoceptors or H2‐histamine receptors in the guinea pig atrium. Although some α1‐adrenoceptor mediated vasoconstriction is produced in the rabbit ear artery and rabbit aorta, the concentrations required are several orders of magnitude higher than those active at the DA2receptor. From these data it is evident that this structural modification can increase both the potency and selectivity of DPDA as a DA2receptor agonist. The potency and selectivity of SK&F 89124 make this agent a useful tool for determination of the functional role of the DA2receptor.
CHARACTERISTICS OF THE DOPAMINE RECEPTORS INVOLVED IN THE ANORECTIC EFFECTS OF APOMORPHINE IN MICE
Authors: DUTERTE‐BOUCHER D. , NAUDIN B. , COSTENTIN J. 
Published: August 2009

Summary—In food‐deprived mice apomorphine injected SC induced a brief (15–30 min) dose‐dependent (30– 150 μg/kg) reduction in food intake. This effect occurred in naive mice as well as in mice habituated to a food deprivation procedure. The anorectic effect of apomorphine (150 μg/kg SC) was antagonized by sulpiride (ID50= 8.6 mg/kg) and by haloperidol (ID50= 66 μg/kg) but domperidone was ineffective (250 μg/kg). Mice submitted to a semi‐chronic (6 d) blockade of dopamine receptors by haloperidol or injected intracerebroventricularly with 125 μg 6‐hydroxydopamine 21 d before testing failed to develop a hypersensitivity to the anorectic effect of apomorphine (60 μg/kg).Although a single apomorphine injection (5 mg/kg) induced tolerance to the hypothermic effect of a second apomorphine injection of 150 μg/kg, it did not modify the anorectic effect. Repeated apomorphine injection (5times5 mg/kg) resulted in a slight but significant reduction in apomorphine‐induced anorexia. A similarly significant reduction was not observed in mice submitted to repeated injections of dexamphetamine (5times5 mg/kg).