bluuebunny/crossref_metadata_2025 huggingface dataset:
Myoplasmic Impedance of the Barnacle Muscle Fiber
Authors: Caillé Jean-Pierre
Published: April 2011

Myoplasmic impedance was measured on a barnacle (Balanus nubilus) single muscle fiber that was placed in a cylindrical cavity to limit the volume and prevent the hydration of the myoplasm. At both ends of the cavity, the myoplasm was in direct contact with an electrolyte solution. When equilibrium with the external medium was reached, the myoplasmic impedance was measured at 10 °C with an impedance bridge at 1000 Hz. The results indicated that the myoplasmic impedance of the muscle fiber is mainly resistive. Treating the myoplasm as a suspension of small conductive particles, we deduced the specific conductivity of the contractile filaments kf and their volume fraction ρ (kf = 2.78 × 10−3 Ω−1 cm−1, and ρ = 0.48). The experimental technique permits an estimate of the specific myoplasmic conductivity in vivo (6.27 × 10−3 Ω−1 cm−1). Finally, a decrease in the pH of the external solution from 10.1 to 4.0 lowered the myoplasmic conductivity by 16%. This may be considered as indirect evidence that the conductivity of the contractile filaments is associated with the protein counter-ions, since Hinke et al. (1973. Ann. N.Y. Acad. Sci. 204, 274–296.) reported evidence that a lowering of pH decreases the number of counter-ions.
The effects of certain drugs on the uptake and release of [3H]noradrenaline in rat whole brain homogenates
Authors: Pylatuk K. L. , McNeill J. H.
Published: April 2011

Twelve drugs were studied with respect to their effects on inhibition of neuronal uptake of [3H]noradrenaline ([3H]NA) and on release of this amine from presynaptic nerve terminals. An in vitro method, using a crude synaptosomal homogenate prepared from rat whole brain, was employed. All drugs tested were found to produce some release of [3H]NA although tyramine was by far the most potent drug in this respect; tripelennamine and cocaine were observed to produce the least release. Studies of inhibition of NA uptake again demonstrated tyramine to be the most potent of the 12 drugs although in this case it did not differ significantly from cocaine and tripelennamine. The remaining compounds also showed decreased accumulation of [3H]NA and all 12 drugs produced uptake inhibition at a lower dose than that required for release of the amine. A correlation between releasing potency and lipophilicity of the compounds indicated that tyramine seemed to be acting in a different manner from the remaining compounds. A correlation between inhibitory potency and lipophilicity could be demonstrated for only six of the drugs, with tyramine, tripelennamine and cocaine showing the greatest deviation from this relationship.
Effects of viloxazine, an antidepressant agent, on biogenic amine uptake mechanisms and related activities
Authors: Lippmann W. , Pugsley T. A.
Published: April 2011

The effects of viloxazine, a clinically effective antidepressant, on noradrenaline (NA) and 5-hydroxytryptamine (5-HT) uptake and various related pharmacological activities were determined and compared to those of the tricyclic antidepressants desimipramine, imipramine, and amitriptyline.Viloxazine inhibited [3H]NA uptake in the mouse and rat heart, being maximally about one half as potent as imipramine with a similar onset, but shorter duration of action than imipramine. The drug did not inhibit [3H]NA uptake in rat medulla or hypothalamus in contrast to desimipramine and imipramine, but it did alter [3H]NA metabolites in a similar manner. Viloxazine, like desimipramine, was a weak blocker of mouse brain 5-HT uptake, but differed from desimipramine as it potentiated 5-HT-mediated functions in the mouse and rat, as did imipramine and amitriptyline, the latter drugs being relatively potent blockers of 5-HT uptake.Viloxazine potentiated the L-DOPA behavioural syndrome in the mouse, antagonized reserpine-induced ptosis and hypothermia in the mouse, and inhibited gastric acid secretion in the rat, but was less potent than the tricyclic antidepressants. No appreciable in vivo inhibition of monoamine oxidase (EC 1.4.3.4.) activity in the mouse was exhibited. Like imipramine, the drug potentiated the ocular effects of L-adrenaline in the rabbit. It was similar to imipramine in potency in potentiating the apomorphine-induced gnawing in the mouse. The drug antagonized oxotremorine-induced hypothermia in the mouse but differed from, the tricyclic antidepressants in not exhibiting the anticholinergic effects of blocking the tremors, salivation and lacrimation.Thus, viloxazine exhibits activities related to the biogenic amines both similar to and different from the tricyclics desimipramine, imipramine, and amitriptyline. These actions appear to be of relevance with respect to the antidepressant action of this drug.
Inotropic and chronotropic responses of the in vivo denervated dog myocardium to dobutamine
Authors: Bolter Chris P. , Ledsome John R.
Published: April 2011

The inotropic and chronotropic responses to dobutamine (DBA) and isoprenaline (ISO) were examined in eight chloralose anaesthetised dogs. Following acute cardiac denervation, heart rate (HR) and contractility (dP/dtmax), measured at a fixed paced atrial rate, were recorded during intravenous infusion of incremental doses of DBA and ISO. Both DBA and ISO elicited increases in HR and dP/dtmax. The increases in dP/dtmax for a one beat per minute increase in HR was 102.0 ± 10.6 mm Hg/s (1 mm Hg (0 °C) = 133.322 Pa), during DBA infusion, and 61.5 ± 8.4 mm Hg/s during ISO infusion. It appeared that the relatively greater inotropic effect of DBA in comparison with ISO was the result of an augmentation of its inotropic activity. DBA infusion was accompanied by a significant increase in mean aortic pressure at all doses examined. An increase in afterload may account for part of the increased inotropic response to DBA.
The relaxant effects of adenosine-5′-α,β-methylenediphosphonate on the longitudinal smooth muscle of the rabbit ileum
Authors: Frew R. , McKenzie S. G. , Bär H. P. , Hutchison K. J.
Published: April 2011

The response pattern of the isolated longitudinal muscle of the rabbit ileum to adenosine-5′-α,β-methylenediphosphonate (APCP) was found to differ from that caused by adenosine or ATP in that the rapid initial phase of relaxation is absent and that at doses above 10 μM a secondary increase of contractile activity occurs in the continued presence of the nucleotide. This secondary phase was attenuated after indomethacin pretreatment and reestablishment of tone with acetylcholine. Theophylline did not modify APCP-induced relaxations while effectively antagonizing those caused by adenosine. It appears that APCP acts via a receptor site or pathway distinct from that of adenosine or ATP.
Modulation of pituitary responsiveness to LHRH by androgens in ovariectomized female rats
Authors: Kulkarni Padmaja N. , Simpson Alan A. , Moger William H.
Published: April 2011

The effect of androgens on pituitary response to luteinizing-hormone-releasing hormone (LHRH) and their ability to modify effects of 17β-estradiol (E2) on pituitary responsiveness to LHRH were tested in ovariectomized rats maintained on a daily dose of 0.25 μg estradiol benzoate per rat for 6 d before androgen administration.Testosterone propionate (TP) (4, 40, 400, or 4000 μg per rat), administered 24 h before LHRH (500 ng per rat), had no significant effect on luteinizing hormone (LH) or follicle-stimulating hormone (FSH) response. Similar doses of dihydrotestosterone (DHT) did not significantly alter the LH response but significantly suppressed the FSH response. Even the lowest dose completely blocked the FSH response to LHRH. TP in combination with 4 or 400 μg of E2 suppressed the stimulatory effect of E2 on both LH and FSH response to LHRH in a dose-related manner. DHT and E2 in combination affected LH response inconsistently, whereas their ratio determined FSH response; there was pronounced inhibition of FSH response in rats given high doses of DHT combined with low doses of E2; DHT inhibition of FSH response in animals receiving 4 μg of DHT with 400 μg E2 was partially overcome by the stimulatory effect of E2. Our results indicate that TP and DHT affect LH and FSH response to LHRH differently. The ratio of androgen to estrogen is important in determining the response to LHRH.
Effects of handling, decapitation, anesthesia, and surgery on plasma noradrenaline levels in the white rat
Authors: Depocas Florent , Behrens W. A.
Published: April 2011

To determine the normal resting level of plasma noradrenaline (NA) in unanesthetized and undisturbed white rats, 20 warm-acclimated rats previously fed a semisynthetic diet were implanted with an intraaortic cannula and allowed to recover for a period of 5 days. They were then placed in a closed metabolism chamber after fitting an extension to the cannula which allowed blood sampling in animals which were unrestricted and unaware of the procedure. The average NA concentration in the plasma was 0.15 ± 0.01 ng/ml as measured by a radioenzymatic method based on formation of [methyl-3H]adrenaline. Levels of noradrenaline in nanograms per millilitre measured in groups of four to five rats after various treatments were as follows: manipulation, 0.63 ± 0.18; decapitation, 1.32 ± 0.25; 5 min after 3% halothane, 0.23 ± 0.01; decapitation under halothane, 0.40 ± 0.03. In five rats fed Purina laboratory chow at room temperature, values were 0.11 ± 0.02 ng/ml and concentration invariably increased after manipulation and after decapitation. The elevated plasma NA concentration in rats cannulated under halothane anesthesia dropped to normal levels in less than 1 h after recovery from anesthesia, thus indicating that tissue trauma associated with cannula implantation does not have a long-lasting effect on plasma NA levels. These results show that special precautions must be taken to ensure minimal sympathetic activity when resting plasma NA levels are to be measured and that data on the effect of various treatments on peripheral levels of NA based on use of anesthetized, manipulated, or decapitated rats are of doubtful significance as use of these procedures result in abnormally high levels of NA in the control animals used for comparison.
Does indomethacin antagonize the effects of peptides and other agents on the coronary circulation of rabbit isolated hearts
Authors: Regoli D. , Barabé J. , Thériault B.
Published: April 2011

The coronary vasodilator effects of substance P, bradykinin, eledoisin, adenosine, and nitroglycerin have been tested in rabbit isolated hearts perfused with physiological medium. It has been found that substance P is the most potent vasodilator and that the peptides are 10–100 times as active as adenosine and nitroglycerin. The effect of bradykinin is reduced by 50% in the presence of indomethacin (2.8–5.6 × 10−6 M) while the actions of the other vasodilator are not influenced. At such concentrations, indomethacin is inactive on its own and blocks the effects of small and intermediate doses of arachidonic acid, the prostaglandin precursor.It is suggested that endogenous prostaglandins do not play any major role in mediating the coronary vasodilation produced by several peptide and nonpeptide agents, but may account for about 50% of the effect of bradykinin.
Effects of acetylcholine on potassium-induced changes of some amino acid uptakes and release in cerebral cortex slices from the rat
Authors: Benjamin A. M. , Quastel J. H.
Published: April 2011

High concentrations (105 μequiv./ml) of potassium ions in the incubation medium bring about reduced uptakes of L-glutamate, L-aspartate, and glycine but not of L-glutamine into rat brain cortex slices incubated aerobically in a physiological saline – glucose medium. The reductions are suppressed by acetylcholine (20 μM – 2 mM) in presence of eserine (0.1 mM) and not by tetrodotoxin (3 μM). The effect of acetylcholine is calcium dependent. It is diminished by atropine but not by d-tubocurarine (1 mM). Protoveratrine (5 μM) inhibition of amino acid uptake is not affected by acetylcholine but it is suppressed by tetrodotoxin. Acetylcholine and tetrodotoxin act independently of each other. Acetylcholine suppresses the potassium-evoked release of endogenous glutamate, aspartate, or glycine from incubated rat brain cortex slices. Its action on release is calcium dependent. Acetylcholine also suppresses the potassium-induced release of amino acids from rat brain cortex slices that have been previously incubated with 2 mM sodium L-glutamate or 2 mM sodium L-aspartate.It is suggested that increased cell concentrations of calcium ions, owing to high concentrations of potassium ions in the incubation medium, cause an increased glial permeability to sodium ions, with a resultant diminution of the sodium gradient. This diminution is considered to be responsible for the diminished concentrative uptake of L-glutamate, L-aspartate, or glycine, and the increased release of these amino acids. Acetylcholine suppresses the permeability change due to high concentrations of potassium ions and reverses the changed sodium gradient and the consequent change in amino acid uptake and release. It would seem that accumulation of acetylcholine in the intracellular spaces may affect glia, as well as neurons, modifying permeability to sodium ions and to various amino acids now assuming importance as possible transmitters.
Mechanical interaction between the ventricles during systole
Authors: Langille B. Lowell , Jones David R.
Published: April 2011

The immediate effect of abrupt alteration in the function of either ventricle on pressures in both ventricles has been examined in rabbits. Increasing left ventricular afterload, by aortic occlusion, caused a marked increase in peak left ventricular pressure (an increase of 44.0 ± 5.7 mmHg, from a mean of 79.4 ± 3.4 mmHg) and simultaneously a significant increase (an increase of 3.8 ± 0.6 mmHg, from a mean of 24.2 ± 1.4 mmHg) in right ventricular pressure. On the other hand, when similar increases in left ventricular pressure were induced by sudden changes in preload no alteration in right ventricular pressure was seen. High-frequency oscillatory infusion of saline into the left ventricle produced coincident oscillations in both ventricular pressures during systole. Left ventricular pressure generation was affected by interventions with right ventricular performance which altered afterload or preload and, although interaction was minimal at normal physiological pressures, a significant interaction was observed during induced systemic hypotension. A direct transference of pressure from right to left ventricle, comparable with that seen in vivo, was also observed when the ventricles of excised hearts in rigor mortis were inflated with saline. It is concluded that mechanical interaction occurs between the ventricles during systole and, consequently, the ventricles cannot be treated as mechanically independent pumps.
Effect of dipyridamole and 6-(2-hydroxy-5-nitro)-benzylthioguanosine on low-frequency-stimulated relaxation in the guinea pig taenia coli
Authors: Baer H. P. , Frew R. , Burnstock G.
Published: April 2011

Isolated guinea pig taenia coli responded to electrical field stimulation at 0.3 s−1 with relaxation which was potentiated from 6 to 230% in the presence of 1–1.5 μM dipyridamole. However, no potentiation was seen in the presence of 10 μM 6-(2-hydroxy-5-nitro)-benzylthioguanosine (HNBTG), another more selective inhibitor of adenosine uptake. Both drugs effectively potentiated the relaxant response to low doses of added adenosine. When complete frequency–response curves were recorded in the range 0.1 to 5 s−1 neither dipyridamole nor HNBTG caused any shift of the curves, although a statistically significant increase in relaxation was again seen in the presence of dipyridamole at 0.3 s−1. Thus, the response of taenia coli to transmural stimulation is not modified by all concentrations of inhibitors of adenosine uptake and the limited effect seen with dipyridamole at 0.3 s−1 may be based on another unknown mechanism. No evidence for or against the purinergic nerve hypothesis can be derived from our experiments.
Effect of folic acid deficiency on pregnant rats and their offspring
Authors: Tagbo I. F. , Hill D. C.
Published: April 2011

Two groups of 63-day-old female Wistar rats were fed a folic acid deficient diet, based on 20% of vitamin-free casein and containing 1% of succinylsulfathiazole, for 5 weeks (group A) and 9 weeks (group B) before being bred, and the same diet was continued through pregnancy and lactation. Three out of eleven (21.3%) and three out of seven (42.9%) rats in groups A and B, respectively, resorbed completely, while no control rat resorbed. No pups from group B survived to weaning. Both groups (A and B) showed depressed feed consumption (although the effect in group A rats was small) and weight gains and increased formiminoglutamic acid excretion in the urine during gestation, and low serum folic acid by the end of lactation. A study of blood components in group A rats revealed leucopenia, granulocytopenia, and increased reticulocyte count. While no congenital deformities were observed in pups from deficient dams, group A and group B dams in contrast to controls produced smaller sized litters with lower birth weights and poor survival rate. Surviving pups from group A dams had decreased weaning weights with significantly lower brain weights and brain DNA per gram of tissue.
Effects of antipsychotic drugs on action potential production in skeletal muscle. I. Chlorpromazine and promethazine
Authors: Buttar H. S. , Frank G. B.
Published: April 2011

The effects of chlorpromazine, an antipsychotic phenothiazine, and promethazine, an antihistaminic phenothiazine, on excitability and action potential production in frog's sartorius muscle fibers were studied and compared. Both drugs produced a local anaesthetic effect which developed slowly over 3 to 5 h with lower concentrations (1 to 15 × 10−6 M) and was only partially reversed by exposing the muscles to a drug-free solution for 3 to 4 h. The resting potential and the input resistance of the muscle fibers were unaffected by drug concentrations which reduced the action potential maximum rate of rise, the threshold current of 2-ms injected pulses and the intracellularly measured threshold depolarization. The effects on the action potential were antagonized in an apparently competitive manner by sodium ions. Thus both drugs depressed excitability and the rising phase of the action potential by inhibiting the specific increase in sodium conductance (gNa) which normally follows an adequate stimulus. It was shown that both drugs also inhibited the secondary rise in potassium conductance (gK) which normally occurs during an action potential. Although quantitatively similar, lower concentrations of chlorpromazine (> 15 × 10−6 M) were more potent and higher concentrations (> 15 × 10−6 M) were less potent than promethazine. The qualitatively identical and the quantitatively similar effects of these two drugs would suggest that the antipsychotic effect produced by some of the phenothiazines is unrelated to their effects on action potential production.
Effects of antipsychotic drugs on action potential production in skeletal muscle. II. Haloperidol: nonspecific and opiate drug receptor mediated effects
Authors: Durham H. D. , Frank G. B. , Marwaha J.
Published: April 2011

The effects of haloperidol, an antipsychotic butyrophenone, on excitability and action potential production in frog's sartorius muscle fibers were studied. This drug produced a local-anaestheticlike effect which developed slowly over 1 to 5 h with lower concentrations (2.7 to 5.3 × 10−6 M) but was completely reversed by exposing the muscles to a drug-free solution. In studies with intracellular microelectrodes, evidence was obtained showing that haloperidol decreased excitability and depressed action potential production by inhibiting the specific increase in sodium conductance (gNa) which normally follows an adequate stimulus. Evidence also was obtained showing an inhibition of the secondary increase in potassium conductance (gK). Haloperidol is structurally related to meperidine and it was found that the inhibition of gNa produced by haloperidol is partially antagonized by low concentrations of naloxone (2.8 × 10−8 and 2.8 × 10−7 M); as was previously shown for meperidine. Thus haloperidol, like meperidine, suppresses action potential production by two mechanisms of action: one, a nonspecific local-anaestheticlike effect; and the other, a specific inhibition of gNa mediated by means of an opiate drug receptor associated with the muscle fiber membrane. Naloxone did not antagonize the effects of chlorpromazine on gNa.
Drug metabolism in cell culture. II. Studies on the metabolic route of DDC analogues
Authors: Racz William J. , Hunter Lynette , Wanless Richard G. F. , McDonald Miriam V. , Moffat Joyce A.
Published: April 2011

To elucidate the major metabolic pathways of DDC analogues, the effect of inhibitors of oxidative and hydrolytic microsomal enzymes on the rate of metabolism of these compounds in chick embryo liver cell cultures has been examined. The metabolism of 3,5-diethoxycarbonyl-2,4,6-trimethylpyridine (Ox-DDC) was inhibited threefold by piperonyl butoxide and SKF-525A (β-diethylaminoethyl-diphenyl-n-propylacetate-HCl), but only onefold by bis(p-nitrophenyl)phosphate (BNPP). This indicates that this compound is metabolized predominately by an oxidative route and hydrolysis is a minor pathway. The half-life of 3,5-diethoxycarbonyl-2,6-dimethylpyridine (4-desmethyl-Ox-DDC) was increased 20-fold by BNPP, but no change was observed with piperonyl butoxide, indicating that this compound is metabolized exclusively by hydrolytic mechanisms. Since both piperonyl butoxide and BNPP produced similar changes in the half-life of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC), it appears that this compound is metabolized equally via oxidative and hydrolytic mechanisms. In contrast to the intact embryo where Ox-DDC is rapidly metabolized and the effect of the agent on δ-aminolevulinic acid (δ-ALA) synthetase (δ-aminolaevulinate synthetase; EC 2.3.1.37) activity is brief and hence porphyrin accumulation does not occur, in cell culture Ox-DDC is metabolized at a rate sufficiently slow so that induction of δ-ALA synthetase does occur.
Prostaglandin-sensitive neurones in cat hypothalamus: relation to thermoregulation and to biogenic amines
Authors: Jell Ralph M. , Sweatman Paul
Published: April 2011

Six-barrelled glass micropipettes were used to record the extracellular activity of neurones in the rostromedial hypothalamus of methoxyflurane-anesthetized cats, and to apply prostaglandins (PG), noradrenaline, 5-hydroxytryptamine, and acetylcholine by microiontophoresis to the vicinity of each neurone encountered. One hundred and sixty-three neurones were tested in 31 cats for responsiveness to prostaglandins and to amines. Thirty-three of these neurones were identified by their responsiveness to peripheral thermal stimulation, which was applied by blowing warm (42 °C) and cold (4 °C) air in the faces of the animals. The remaining neurones were functionally unidentified. Thirty-six prostaglandin responses were evoked in 27 neurones. Ten percent of those tested responded to PGE1, 17% to PGE2, and 17% to PGF2α. The majority of these responses (69%) were fast (short latency, rapid termination) type. Slow onset and termination were typical of 25% of the responses. Of 21 neurones which were sensitive to PGE1 or PGE2 17 (77%) were thermoresponsive, 10 being cold excited and 7 warm excited. Five neurones were sensitive only to PGF2α, and all were nonthermoresponsive. Neurones sensitive to PGE1 or PGE2 were significantly more likely to respond to NA (p < 0.05) and 5HT (p < 0.01) than PGE-insensitive neurones. Amine responses were not altered by simultaneous application of PGE. The data support the view that PGE2 and PGF2α are more active in this region than PGE1, and that the action of either PGE1 or PGE2 is specific to thermoregulatory neurones in the rostral hypothalamus. Evidence has been obtained for a common site of action of PGE and the amines NA and 5HT on thermoregulatory neurones in the cat.
Action of a β-bungarotoxin on autonomic ganglia and adrenergic neurotransmission
Authors: Kato A. C. , Pinto J. E. B. , Glavinović M. , Collier B.
Published: April 2011

A β-bungarotoxin was isolated from the venom of Bungarus multicinctus by column chromatography on Sephadex G-50 and SP-Sephadex. The toxin produced presynaptic effects on neuromuscular transmission with characteristics similar to those described by others. In a sympathetic ganglion, the toxin increased spontaneous acetylcholine (ACh) release and decreased ACh release evoked by preganglionic nerve stimulation. The toxin did not block the response of isolated ileum to cholinergic nerve stimulation, did not block the release of noradrenaline from the adrenergic nerve terminals of a nictitating membrane preparation, and did not alter the responses of smooth and cardiac muscle preparations to noradrenaline. It is suggested that the specificity of β-bungarotoxin for certain nerve terminals is related either to selective binding of the toxin or to the selective presence of a necessary substrate for its action. An attempt to show selective binding of 125I-toxin to cholinergic nerve terminals in skeletal muscle was not successful.
Angiotensinase activity and angiotensin receptor binding in guinea pig aorta
Authors: Morvan Patrick Le , Palaic Djuro , Ferguson Dragana
Published: April 2011

The angiotensinase (EC 3.4.99.3) activity of the subcellular fractions of guinea pig aorta has been studied in relation to their [14C]angiotensin binding capacity. The enzyme activity occurs in the following decreasing order: supernatant > plasma membrane fraction > 105 000 × g pellet > mitochondrial fraction. The specific binding of [14C]angiotensin to these fractions follows the same pattern. Pretreatment of the subcellular fractions at 47 °C for 20 min was performed in an attempt to differentiate binding of angiotensin to the pharmacological receptor from binding to the destroying enzymes. This procedure decreased the angiotensinase activity in the plasma membrane fraction only whereas the specific binding of [14C]angiotensin to this fraction was not significantly decreased, suggesting that the plasma membrane angiotensinase is a thermolabile enzyme.
Increased circulating plasma catecholamines and plasma renin activity in dogs after chemical sympathectomy with 6-hydroxydopamine
Authors: Porlier Gérald A. , Nadeau Réginald A. , Champlain Jacques de , Bichet Daniel G.
Published: April 2011

Circulating plasma catecholamines, plasma renin activity, and other variables were measured in unanesthetized dogs before and after chemical sympathectomy with 6-hydroxydopamine (6-OHDA, 50 mg/kg). Chemical sympathectomy resulted in an immediate fall in mean arterial blood pressure and a delayed reduction in heart rate. Significant increases in plasma glucose and lactate concentrations, circulating plasma catecholamines, and plasma renin activity were found 24 h after 6-OHDA treatment. Circulating catecholamine levels decreased rapidly as time elapsed after sympathectomy and were half the initial values after 2 weeks. Plasma renin activity remained elevated during the 1st week after 6-OHDA treatment and returned to control levels during the 2nd week. Significant correlations were found between circulating catecholamines and heart rate mean arterial pressure, and plasma glucose and lactate concentrations. A significant correlation was also found between plasma renin activity and the mean arterial blood pressure. These results confirm that the adrenal medulla increases its catecholamine secretion rate into the circulation to compensate for the loss of adrenergic innervation after 6-OHDA treatment. They also indicate that the rennin–angiotensin system represents another important compensatory mechanism for circulatory homeostasis in sympathec-tomized animals.
Possible mechanism for the frequency-dependent increases in the cardiac contraction in monkey
Authors: Singal Pawan K. , Khatter J. C. , Prasad K.
Published: April 2011

The effects of various interventions on the frequency-dependent increases in the contractility of the papillary muscles of monkeys were investigated. Ouabain (10−6 M) and KCl-free Krebs–Ringer solution, which are known to inhibit membrane Na+, K+-ATPase (EC 3.6.1.3), abolished the frequency-dependent increases in the contractility of the papillary muscles. Epinephrine (4.5 × 10−8 M) or quinidine (1.3 × 10−5M), which are known not to inhibit the membrane Na+, K+-ATPase at these concentrations, did not alter the frequency-dependent increases in the contractility. These results indicate that the frequency-dependent increases in the contractility might be mediated through an inhibition of the sarcolemmal Na+, K+-ATPase.
Inhibition of cerebral cortical neurones by a 5-hydroxytryptaminergic pathway from median raphé nucleus
Authors: Sastry B. S. R. , Phillis J. W.
Published: April 2011

Recent observations made in our laboratory have shown that metergoline is a selective 5-hydroxytryptamine (5-HT) antagonist in the cerebral cortex. Fluoxetine is a reportedly selective 5-HT neuronal uptake blocker. In the present investigation these drugs have been used to examine the existence of a putative 5-HT input to the cerebral cortex. In rats anaesthetized with a mixture of methoxyflurane, nitrous oxide, and oxygen, stimulation of the median raphé nucleus or of the ipsilateral cortical surface and iontophoretically applied 5-HT decreased the firing of the deep cerebral cortical neurones. Metergoline antagonized the 5-HT-induced depression and reduced the duration of inhibition produced by raphé nucleus stimulation. The inhibition produced by cortical surface stimulation was unaffected. Fluoxetine potentiated and prolonged the inhibition of cortical neurones induced by either 5-HT application or by raphé nucleus stimulation. These results suggest that the cerebral cortical neurones are inhibited by an ascending 5-HT-containing pathway.
The effect of hypoxia on prostaglandin output and on tone in isolated coronary arteries
Authors: Kalsner Stanley
Published: April 2011

The relationship between bath [Formula: see text] intramural prostaglandin synthesis, and vessel tone in isolated coronary arteries of cattle was studied. The basal output of prostaglandin under 95% O2 – 5% CO2 (580 mmHg) was elevated markedly when the [Formula: see text] was decreased to 47 mmHg but extreme hypoxia (9 mmHg) sharply curtailed output. The coronary vessels responded to 47 mmHg with relaxation but they contracted when the [Formula: see text] was decreased further to 9 mmHg. Known inhibitors of prostaglandin synthesis attenuated both the hypoxia-induced relaxations and contractions. Analysis of the effects of extreme hypoxia and of inhibitors of prostaglandin synthesis on tone indicated that both suppress prostaglandin production. It is concluded that coronary prostaglandin synthesis is accelerated by hypoxia unless the oxygen deprivation is so severe as to limit the availability of oxygen for synthesis.
L'effet du pH, du Mg2+ et de l'ATP sur la conductivité électrique du protoplasme musculaire du balane
Authors: Caillé Jean-Pierre
Published: April 2011

not available
Improved cold tolerance and its mechanism in cold-acclimated rats by high fat diet feeding
Authors: Kuroshima Akihiro , Doi Katsuhiko , Yahata Takehiro , Ohno Tomie
Published: April 2011

Cold tolerance and metabolic responses to cold were studied in cold-acclimated rats on high fat diet (CAHF). Cold tolerance at −5 °C was assessed by fall of colonic temperature of clipped rats after 18 h of fasting. Rate of fall in colonic temperature was greatest in warm-acclimated control rats (WAST), slowest in cold-acclimated rats on standard diet (CAST), and remained unchanged in CAHF during cold exposure for 240 min. Increment in blood free fatty acid (FFA) concentration 80 min after cold exposure was greatest in WAST, less in CAST, and least in CAHF. Blood glucose decreased similarly in WAST and CAST after cold exposure, while it remained unchanged in CAHF. Blood β-hydroxybutyrate also increased similarly in WAST and CAST, while it did not change in CAHF. Nonshivering thermogenesis tested by noradrenaline was greatest in CAHF, followed by CAST and WAST. Shivering induced by cold exposure was less pronounced in CAST than in WAST and did not develop in CAHF; changes in colonic temperature were inversely related to the extent of shivering during cold exposure for 90 min.These results suggest that an integrating effect of cold and high fat diet could improve cold tolerance much more than cold acclimation itself, possibly through enhanced nonshivering thermogenesis caused by metabolic modifications such as increased lipid use and gluconeogenesis.
Simulation of oviductal ovum transport
Authors: Portnow J. , Hodgson B. J. , Talo A.
Published: April 2011

The present note describes a Monte Carlo simulation of ovum transport in the rabbit oviduct. Ova execute a random walk through a one-dimensional oviduct and the jump probabilities at each point are obtained from in vitro electrical recordings of smooth muscle activity. Simulated transport are compared with experimental findings at 18 and 66–68 h after human chorionic gonadotropin injection.
Alteration of exogenous norepinephrine caused by electrical 'field' stimulation and its role in poststimulant relaxation
Authors: Wyse D. George
Published: April 2011

Arterial strips from rat tail, rabbit ear, and dog mesentery, which are partially contracted by norepinephrine (NE), relax below the initial level of contraction in a frequency-dependent manner after cessation of transmural electrical stimulation. Antagonism of poststimulant relaxation by several pharmacologically unrelated agents suggests that the phenomenon is probably not due to release of a specific dilator neurotransmitter. Indeed, electrical stimulation of modified Krebs bicarbonate solution (contains EDTA) and NE in the absence of tissue abolishes the ability of the mixture to elicit a contraction when transferred to a second bath containing unstimulated tissue. Electrical stimulation does not measurably alter bath pH and temperature nor the ability of NE and 5-hydroxytryptamine to elicit contractions when they are added to the bath after stimulation has ended. Electrical stimulation (30-s train, 16 Hz, 0.5 A, rectilinear pulse width 0.5 ms) of modified Krebs bicarbonate solution and radiolabelled NE in the presence or absence of tissue results in alteration of a major portion of the labelled NE with appearance of several unidentified products. High concentrations of a known NE metabolite (3,4-dihydroxyphenylglycol) interfere with the ability of NE to maintain a contraction, and the possibility that NE breakdown products may interfere with NE's pharmacological action as an additional mechanism for a portion of poststimulant relaxation is not excluded. It is concluded that 'field' stimulation under the present conditions causes oxidation of NE in spite of the usual precaution of adding EDTA to the bath solution.
Adenosine uptake by the isolated epithelium of guinea pig jejunum
Authors: Kolassa N. , Stengg R. , Turnheim K.
Published: April 2011

The uptake of [8-14C]adenosine by the isolated epithelium of guinea pig jejunum was faster than that of inosine, hypoxanthine, or adenine. The initial velocity of adenosine uptake from both the luminal and the antiluminal side of the epithelium exhibited saturation kinetics. The apparent Km, V, and passive permeability of luminal adenosine uptake were all lower than the corresponding values of antiluminal uptake. p-Nitrobenzyl-thioguanosine inhibited adenosine uptake from both the luminal and the antiluminal side, whilst hexobendine decreased the uptake only from the antiluminal side of the epithelium. The results suggest that adenosine enters the intestinal epithelium by a carrier-mediated process in addition to passive diffusion. The antiluminal transport system for adenosine seems similar to that of other tissues with respect to hexobendine inhibition; the luminal transport mechanism, however, exhibits different properties, being insensitive to hexobendine.
Myotropic actions of angiotensin and noradrenaline in strips of rabbit aortae
Authors: St-Louis J. , Regoli D. , Barabé J. , Park W. K.
Published: April 2011

The myotropic effects of angiotensin II (ATII), some analogues and fragments of ATII, and noradrenaline (NA) have been studied in rabbit aorta strips, in vitro. Contractions elicited by NA consist of an initial rapid and of a slow late phase, while ATII produces a slow and gradual increase of tension, especially at low concentrations. A good correlation has been shown to exist between the time required to increase tension by 50% and the concentration of ATII or the pD2 values of various angiotensins. These results suggest that the pattern of the contractions produced by NA and ATII is influenced by the different diffusion rates of the two agents. Aortic strips contracted by NA maintain a stable plateau of contraction for more than 20 min, while tension in those stimulated by maximal concentrations of ATII fades. This fade persists in the presence of indomethacin, of high concentrations of extracellular Ca2+, and does not depend on the metabolism of the peptide.Extracellular Ca2+ plays an important role in the stimulation or rabbit aorta strips by ATII and NA, but does not effect the binding of ATII to its specific receptors over a wide range of concentrations, and reduces slightly the binding of NA. The ratio of maximum response (ATII–NA) is influenced by external Ca2+ and corresponds to 0.54 in the presence of low Ca2+ (0.01 mM), and to 0.86 in the presence of 2.5 mM Ca2+. Both agonists maintain a fraction of their myotropic effect in tissues exposed to Ca2+-free medium for short periods (10−20 min) but are almost inactive after 60 min of Ca2+ deprivation. It is concluded that a fraction of the myotropic effect of both NA and ATII is independent of external Ca2+. Readdition of Ca2+ (1.5 mM) at the peak of the residual effects obtained in absence of Ca2+ restores full control response to both agents. When the same intervention is repeated at different times after washout of the drug only the strips treated with ATII show a progressively decreasing contractile response. This indicates that ATII remains in the active form in the proximity of the receptors for several minutes after washing, while NA does not.The administration of the antagonists (8-Gly-ATII for ATII and phentolamine for NA) or the removal of external Ca2+ while maintaining the infusion of the two stimulants is followed by relaxations more rapid than that produced by the washout of ATII, but not of NA. A good correlation has been shown to exist between the rates of the relaxations induced by 8-Gly-ATII and the pD2 values of various angiotensins.The results suggest that the major difference between the actions of ATII and NA in rabbit aortae resides in the duration of the drug−receptor interaction. The drug−receptor complex of the peptide appears to be more stable than that of the catecholamine and this may explain the higher (with respect to NA) affinity of ATII for its aortic receptors.
Effect of osmolality on renal medullary Na-K-ATPase activity in the postobstructive kidney
Authors: Knox W. H. , Sax J. A. , Wilson D. R. , Sen A. K.
Published: April 2011

The aim of this study was to determine the effect of changes in osmolality on the reduced renal medullary Na-K-ATPase (EC 3.6.1.3) activity of the postobstructive kidney. The effect of osmolality on renal medullary Na-K-ATPase activity was studied by incubating tissue slices from sham-operated and bilaterally obstructed rats in media with osmolality varied before enzyme isolation using sodium chloride, choline chloride, or sucrose. Both sham-operated and bilaterally obstructed rat renal medullary enzyme showed a similar increase in activity with increased osmolality due to sodium chloride. Medullary Na-K-ATPase from the postobstructive kidney also showed increased activity with osmotic changes induced by choline chloride or sucrose. It is proposed that the decrease of Na-K-ATPase activity observed after bilateral ureteral obstruction is due, at least in part, to the loss of the solute concentration gradient in the kidney.
Massive liver enlargement accompanied by decreased drug metabolism. Effect of anterior pituitary extract on hepatic ultrastructure, zoxazolamine paralysis, and metabolism in the rat
Authors: Szabo S. , Garg B. D. , Kourounakis P. , Tuchweber B.
Published: April 2011

The relationship between liver enlargement and drug metabolism was investigated in female rats. Hepatomegaly (e.g., 31% increase in liver weight in a 17-day experiment) was induced by injection of lyophylized anterior pituitary (LAP) extract The liver enlargement seemed to be due to an increase in the number and the size (enhanced water content and PAS-positive material) of hepatocytes. Electron microscopic examination of the liver revealed slight proliferation of the smooth endoplasmic reticulum and pronounced fragmentation and dilation of the rough endoplasmic reticulum. Zoxazolamine paralysis time was significantly prolonged (+55% and +102%) after 4 and 17 days, respectively, of treatment with LAP. Metabolism of zoxazolamine by the 9000 g supernatant fraction of the liver of rats given LAP for 17 days was reduced by 73%. Thus, the marked hepatomegaly induced by LAP was associated with a prolonged action of the drug which may result from a decrease in hepatic drug metabolism.
Role of transmitters in mediating hypothalamic control of electrolyte excretion
Authors: Morris M. , McCann S. M. , Orias R.
Published: April 2011

Changes in urinary volume and electrolyte excretion were monitored after the injection of cholinergic and monoaminergic drugs into the third cerebral ventricle of conscious male rats made diuretic by an intravenous infusion of 5% dextrose. A natriuretic and kaliuretic response was induced by the intraventricular injection of norepinephrine (NE) or carbachol, whereas dopamine (DA) had no effect. The β-receptor stimulator isoproterenol (ISO) induced an antinatriuretic and antikaliuretic effect.Intraventricular injection of the α-adrenergic blocker phentolamine abolished the natriuretic response to NE and carbachol and to intraventricular hypertonic saline (HS). By contrast, the β-adrenergic blocker propranolol induced a natriuresis and kaliuresis when injected alone and an additive effect when its injection was followed by NE or HS. Propranolol potentiated the natriuretic response to carbachol. Cholinergic blockade with atropine diminished the response to NE and blocked the natriuretic response to HS. It is suggested that sodium receptors in the ventricular wall can modify renal sodium excretion via a stimulatory pathway involving cholinergic and α-adrenergic receptors and can inhibit sodium excretion via a tonically active β-receptor pathway.
Myocardial lipid metabolism in cardiac hyper- and hypo-function. Studies on triiodothyronine-treated and transplanted rat hearts
Authors: Vasdev S. C. , Korecky B. , Rastogi R. B. , Singhal R. L. , Kako K. J.
Published: April 2011

Lipid composition of the myocardium and in vitro lipid metabolism were studied in hearts from young rats after 30 days of treatment with triiodothyronine (100 μg/kg per day) and in heterotopically isotransplanted hearts of inbred adult rats 6 days after surgery. The former served as an experimental model of cardiac hyperfunction, while the latter, empty beating hearts, served as a model of cardiac hypofunction. In hearts from hyperthyroid animals the concentration of phosphatidylcholine, phosphatidylethanolamine, cardiolipin, and the incorporation of 14C-labelled palmitic and erucic acid into these phospholipids were increased significantly as compared with controls. In contrast, the triglyceride concentration and the incorporation of palmitate into triglyceride were significantly decreased. In transplanted hearts, the phospholipid concentration and the incorporation of 14C-labelled fatty acids into phospholipids were significantly decreased as compared with the hearts of the inbred host rats of the same age. The results indicate that the mechanical performance of the heart affects the phospholipid composition, which maybe a reflection of increased or decreased proliferation of subcellular membranes in sustained cardiac hyper- or hypo-function.
Redistribution in left ventricular regional flow following acute right ventricular pressure overload
Authors: Sestier Francois , Mildenberger Richard R. , Klassen Gerald A.
Published: April 2011

The left ventricular dysfunction following acute pulmonary hypertension remains unexplained. We wondered if acute pulmonary hypertension could alter the transmural flow distribution within the left ventricular myocardium, independent of coronary flow and perfusion pressure. We used a canine preparation in which the left coronary system was perfused at constant flow and induced a two- to three-fold increase in pulmonary artery pressure by banding the pulmonary artery. Regional myocardial blood flow of the left coronary system was measured using radioactive microspheres, injected into the left coronary system before and after 10–30 min of banding of the pulmonary artery. The left ventricular subendocardial: epicardial ratio fell by 12 and 31% (p < 0.05) of control value, 10 and 30 min, respectively, after banding of the pulmonary artery, the total flow to the left coronary system being kept constant. Left atrial mean pressure increased from 2.9 ± 2.4 to 3.6 ± 1.9 and 6.0 ± 2.1 (p < 0.05) following banding. The mechanism of the redistribution of coronary flow may relate to inappropriate vasodilation of the right septal myocardium with consequent relative left ventricular subendocardial hypoperfusion which might aggravate left ventricular ischemia in the presence of hypotension and hypoxia.
Effect of different drugs on a cytochrome c – phospholipid bilayer membrane
Authors: Singer Michael A.
Published: April 2011

Liposomes were prepared from dipalmitoyl phosphatidylcholine and dicetylphosphate and their interaction with the extrinsic membrane protein cytochrome c examined in terms of changes in 22Na permeability, electrophoretic mobility, protein binding, and motion of an incorporated spin label. The amount of cytochrome c bound displays no significant temperature dependence over the temperature range studied (from 30 to 55 °C) whereas cytochrome c causes an increase in 22Na efflux only above the phospholipid phase transition temperature. Interaction of the protein with the lipid vesicles causes no significant disturbance in the bilayer interior as monitored by the motion of the incorporated spin probe. The drugs 2,4-dinitrophenol and ethacrynic acid, both of which increase the magnitude of the vesicle negative charge, enhance both cytochrome c binding and its effect on 22Na permeability. In contrast, the local anesthetic dibucaine, which induces a positive surface charge on these liposomes, reduces both protein binding and the protein-induced increase in 22Na efflux. Finally, the chemicals butylated hydroxytoluene, 2-tert-butylphenol, and tert-butylbenzene, all of which cause early 'melting' of the phospholipid fatty acyl chains, block the capacity of cytochrome c to enhance 22Na permeability while having no effect on its binding to the vesicles.