bluuebunny/crossref_metadata_2025 huggingface dataset:
Lithium suppresses elevated behavioural activity and brain catecholamines in developing hyperthyroid rats
Authors: Rastogi Ram B. , Singhal Radhey L.
Published: April 2011

Neonatal hyperthyroidism in rats induced by daily administration of L-triiodothyronine for 30 days since birth resulted in a significant rise in mobility and the metabolism of brain norepinephrine and dopamine. Whereas administration of lithium carbonate (60 mg/kg ip) to normal rats for 6 days produced no effect on spontaneous locomotor activity and increased the synthesis and possibly release of this monoamine in several brain regions, this antimanic drug antagonized the L-triiodothyronine-stimulated increases in mobility as well as norepinephrine and dopamine metabolism of hypothalamus, midbrain, striatum, and cerebral cortex. Furthermore, lithium treatment restored the activity of catechol-O-methyl transferase (EC 2.1.1.6) in young hyperthyroid rats to virtually normal limits. Our data suggest that antiphasic or damping effects of lithium upon mood swings is controlled, at least in part, by catecholaminergic systems in the brain. The interrelationship between brain catecholamines and thyroid hormone seems to be important to our understanding of the action of lithium in affective illness.
Amino acid content of chronic undercut cortex of the cat in reletion to electrical afterdisctrarge: comparison with cobalt epileptogenic lesions
Authors: Koyama I. , Jasper H.
Published: April 2011

Chronic undercutting of cerebral cortex in the cat for survival periods of 9 to 308 days was found to cause an increase in duration of epileptiform electrical, afterdischarge and a significant decrease in content of glutamic acid, GABA, and aspartic acid as compared with homologous cortex of opposite hemisphere. These changes were comparable (though less marked) with changes previously found in cobalt-induced experimental epileptogenic lesions. Rate of release of GABA, glutamic acid, and aspartic acid into superfusates of undercut cortex at rest was higher in undercut cortex and was increased further by electrical stimulation. It was concluded that chronic partial denervation of cerebral cortex causes prolonged changes in metabolism or storage of glutamic acid, GABA, and aspartic acid probably related to increased tendency to prolonged epileptiform discharge similar in some respects (though not all) to changes observed in cobalt-induced cortical epileptogenic lesions. However, electrical afterdischarge threshold was not reduced in chronically undercut cortex and prolonged afterdischarge was not necessarily related to concentration of GABA in superfusate from undercut cortex, suggesting that factors other than amino acid metabolism may be also involved in mechanisms of epileptogenesis in undercut cortex.
Bicuculline, benzyl penicillin, and inhibitory amino acids in the spinal cord of the cat
Authors: Krnjević K. , Puil E. , Werman R.
Published: April 2011

Bicuculline methochloride (BMC), applied by microiontophoresis, tends to depolarize spinal motoneurons and lower their input resistance. With approximately equal iontophoretic currents of γ-aminobutyric acid (GABA) and BMC, there is an almost equal chance of observing no change, a potentiation, or a depression of the GABA-evoked conductance increase. A block of the GABA action is seen consistently only when the iontophoretic current of BMC is at least double that of GABA. Under these conditions BMC can selectively antagonize GABA without blocking the effects of glycine, though the latter can also be blocked by larger amounts of BMC. BMC also regularly eliminates the usual apparent desensitization to GABA. This may be due to depression of GABA uptake by BMC, which would also account for its potentiating action at lower relative doses. Comparable effects are observed with iontophoretic applications of benzyl penicillin (BP); but even large doses of BP produce no definite change in membrane properties or in conductance increase evoked by GABA or glycine.
Some effects of organic anions on excitability and excitation–contraction coupling in frog skeletal muscle
Authors: Foulks J. G. , Perry Florence A.
Published: April 2011

When substituted for external chloride, organic anions differed markedly from one another in the extent to which they produced hyperexcitability and in the direction and intensity of their effects on twitch tension in frog skeletal muscle. All of the anions studied reduced the threshold [K]0 for K contractures and most enhanced twitch tension. Among carboxylate anions, increasing the size of the attached apolar hydrocarbon chain led to decreased hyperexcitability and to reduction in the amplitude of twitches and maximum K-contractures, butyrate being the most effective depressant of these responses. Sulfonate anions produced much less conspicuous changes in contractile performance. With γ-hydroxybutyrate, the introduction of a polar group on the hydrocarbon terminus resulted in twitch enhancement and partial restoration of maximum K-contracture tension. The depressant effect of butyrate on K contractures was partially overcome by a fivefold increase in the external concentration of calcium but twitches were unaffected. Perchlorate (12 mM) effectively antagonized the depressant actions of butyrate on twitches as well as K contractures. Most of the effects of these anions were prompt in onset. Impairment of contractile performance by butyrate was not accompanied by appreciable changes in membrane resting or action potentials or in the relation between [K]0 and membrane potential, and took place in spite of reduction in K-contracture threshold. Such effects must result from alteration in excitation–contraction coupling, possibly by interference with the binding of divalent cations to the membrane surface.
The effects of alcohol upon cooling rates of humans immersed in 7.5 °C water
Authors: Hobson G. N. , Collis M. L.
Published: April 2011

The effects of the ingestion of a moderate dose of alcohol, a known vasodilator, upon the cooling rate of four human subjects immersed in 7.5 °C water for periods of time ranging from 38 to 75 min is reported. In three of the cases the cooling rate was retarded, in no case was it accelerated. This result, while lacking statistical significance, has not previously been reported. The difficulties attendant upon such research are noted.
Effect of propranolol on renin release in the dog
Authors: Yun John C. H. , Kelly Gerald D. , Bartter Frederic C.
Published: April 2011

Infusion of d,l-propranolol in both anesthetized and conscious dogs caused decreases in heart rate (HR), plasma renin activity (PRA), and plasma aldosterone. There was no consistent change in mean arterial blood pressure, plasma renin substrate concentration, packed cell volume, plasma potassium, or plasma sodium concentration following the infusion of propranolol. In five conscious animals, infusion of propranolol (1 mg/kg followed by 0.47–0.65 mg kg−1 h−1) reduced HR from 117.6 ± 4.0 beats per minute (mean ± SE) during control periods to 73.2 ± 2.0 beats per minute (P < 0.005) 90 min after the start of infusion. PRA decreased from 9.97 ± 1.79 ng ml−1 h−1 during control periods to reach 1.50 ± 0.42 ng ml−1 h−1 (P < 0.005) at the end of the 90-min infusions. Plasma aldosterone also decreased during this time from 17.60 ± 1.93 ng% during control periods to reach 6.64 ± 0.98 ng% (P < 0.005). The data suggest that propranolol at the dose administered suppresses renin and aldosterone secretion in unstimulated dogs. They suggest also that β-receptor activity contributes to basal renin release.
Effect of norepinephrine on intramyocardial distribution of blood flow in normal and ischemic myocardium
Authors: Dumont L. , Lelorier J.
Published: April 2011

Using labelled microspheres, the effect of norepinephrine (NE) infusions (15 μg and 30 μg/min) on coronary blood flow and its intramyocardial distribution during ischemia was studied. The results reported here show that in the ischemic myocardium, the ratio of endocardial to epicardial flow was 0.67. This value became 1.0 in dogs receiving NE at a dose of 30 μg/min. Since an adrenergic discharge is known to accompany angina in man, these data suggest that an imbalance between the endocardial and epicardial blood flow might not be present in this clinical condition.
Isometric and isotonic contractions in airway smooth muscle
Authors: Stephens N. L. , Niekerk W. Van
Published: April 2011

Canine tracheal smooth muscle was used as an in vitro model of smooth muscle in intrapulmonary airways to determine whether active tension curves derived from isometric and isotonic muscles are similar, and thus resemble striated muscle in this respect. Isometric, isotonic after-loaded, and isotonic free-loaded contractions elicited at different lengths and loads, were analysed. The data demonstrate that length–tension (L–T) diagrams are different in these various types of contractions for electrically and carbachol driven tracheal smooth muscles strips. In general, at any given length active tension is less in isotonic and free-loaded modes of contraction as compared with isometric. We conclude that the ability to actively develop tension at a given length in airway smooth muscle depends on the mode of contraction.
Receptors for bradykinin in rabbit aortae
Authors: Regoli D. , Barabé J. , Park W. K.
Published: April 2011

Rabbit aorta strips respond to bradykinin (BK) and to the C-terminal fragment of BK, the octapeptide 1-8 BK (Octa) with sustained contractions which are presumably due to the stimulation of specific receptors, because they remain unchanged in presence of phentolamine, methysergide, mepyramine, 8-Leu-ATII, and indomethacin. Experimental dose–response curves of BK and Octa are very similar to the theoretical curves predicted by the mass-action law and show the classical hyperbolic shape; ratios of doses producing 16% and 84% of maximum effects are 1:20 for Octa and 1:19 for BK. The relations of stimulus and effect are linear, suggesting that the extents of the contractions are proportional to the number of receptors occupied by the agonists.Structure–activity studies performed with fragments and analogues of BK and with analogues of Octa have shown that 8-Phe is essential for activation of the aortic receptor, and plays an important role for the affinity. The octapeptide 1-8 sequence is more favorable than the nonapeptide, because BK (pD2 = 6.40) is less potent than Octa (pD2 = 7.19) and 9-Ala BK is a partial agonist.Antagonists for both Octa and BK have been found by replacing 8-Phe with aliphatic residues (Ala, Nle, Leu, Leu-OMe) in the octapeptide. Affinities of 8-Leu-Octa (pA2 = 6.75) and 8-Leu-OMe-Octa (pA2 = 6.66) for the aortic receptors are fairly high and the antagonism appears to be of the competitive type because pA2 – pA10 is close to 0.95 for both compounds.The inhibitory effect of these two compounds are specific for Octa and BK. It is concluded that rabbit aortae contain a new type of receptor for BK, different from those found in the intestine and the uterus of several species.
Polymers of biogenic amines
Authors: Richardson John B. , Bouchard Thérese , Boyd Gordon N.
Published: April 2011

Biogenic amines, with a primary amino group, were reacted with glutaraldehyde to form insoluble precipitates. These precipitates had distinctive ultrastructural features upon further reaction with osmic acid. When tested in vitro, they had biological activity and showed evidence that part of this biological activity was due to the large polymer of glutaraldehyde and amine. Experiments with isotope-labelled amines in the production of these precipitates showed that the precipitated polymers were not completely stable and that free amine was liberated from them. Since they were not stable, they could not be used for the morphological localization of the amines as had been intended, but they may have some use as depot drugs or in the immunization of animals against these amines.
Reduced hyperglycemic action of glucagon in cold-acclimated rats, especially in venous drainage from brown adipose tissue
Authors: Kuroshima Akihiro , Doi Katsuhiko , Ohno Tomie
Published: April 2011

Glucagon infusion at a rate of 2 μg/min for 30 min into warm-acclimated rats induced a marked rise of glucose concentration in venous blood both in the external jugular vein and in Sulzer's vein from the interscapular brown adipose tissue. In cold-acclimated rats the increase in the concentration of glucose was significantly reduced in the former vein and abolished in the latter one. These results suggest an enhanced use of glucose in the brown adipose tissue in cold-acclimated animals under the influence of glucagon.
Stimulation of cerebral cortical synaptosomal Na-K-ATPase by biogenic amines
Authors: Lee S. L. , Phillis J. W.
Published: April 2011

The amines noradrenaline, dopamine, 5-hydroxytryptamine, and histamine (0.01–0.5 mM) enhanced the activity of Na-K-ATPase (EC 3.6.1.3) in rat cerebral cortical synaptosomal fractions. The activities of Mg-ATPase and Ca-Mg-ATPase were not significantly affected. No stimulation of Na-K-ATPase occurred in the presence of chelating agents (0.5 mM EGTA or EDTA) unless 0.5 mM calcium had also been added to the incubation medium. These results are consistent with the hypothesis that amines depress cerebral cortical neurones by activation of an electrogenic sodium pump. Calcium ions appear to be involved in this process.
An analysis of the action of lanthanum on aortic tissue from normotensive and spontaneously hypertensive rats
Authors: Goldberg M. T. , Triggle C. R.
Published: April 2011

Significant tension development resulting from the administration of lanthanum salts (La3+) to isolated aorta tissues was observed in preparations from the spontaneously hypertensive rat (SHR) but not in preparation from age-matched normotensive Wistar rats (NWR). The response to La3+ was significantly greater in tissues maintained in bicarbonate-buffered Krebs than observed in bicarbonate and phosphate-free HEPES-buffered Krebs. At least part of the La3+ response in the bicarbonate- and phosphate-buffered solutions was due to a pH shift and could be mimicked by raising the extracellular hydrogen ion [H+] concentration. However, a direct action of La3+ on excitation–contraction coupling could be observed in HEPES-buffered solutions where the addition of La3+ also resulted in tension development but no significant pH change; this action of La3+ was found to be resistant to inhibition by maintenance in a Ca2+-free medium and (or) D-600 pretreatment suggesting an intracellular action for La3+.The paradoxical response to both H+ and La3+ in the SHR aorta suggests that the muscle membrane may be more permeable to these ions and, in addition, suggests that the membrane and (or) intracellular calcium stores in this tissue may also be more labile than those in the normotensive controls.
Electrocardiograms of male rats fed rapeseed oil
Authors: Hunsaker W. G. , Hulan H. W. , Kramer J. K. G. , Corner A. H.
Published: April 2011

Frontal plane electrocardiograms (standard limb leads) were recorded on male Sprague–Dawley rats fed for 14 weeks on semisynthetic diets containing 20% (by weight) of Brassica napus cv. Tower or B. campestris cv. Span rapeseed oil or fractions isolated from Span rapeseed oil. Control diets were rat Chow or semisynthetic diets containing 20% (by weight) of either safflower oil or corn oil. The amplitude of the P, Q, R, S, and T waves, the duration of the P wave, QRS complex, and P–R interval, and the cardiac rate were measured in the electrocardiograms and differences between groups compared statistically. While there were statistically significant differences in the amplitude of some of the wave forms, there were no consistent differences which could be attributed to the feeding of rapeseed oil or its fractions. The duration of the P wave and the QRS complex were significantly longer in some of the control groups than those in most of the treated groups. There was no correlation between the presence of a Q wave and the incidence of myocardial lesions in any group. Cardiac rate was essentially the same in all groups.
Bile-salt-dependent and independent choleresis induced by bucolome in the rat
Authors: Kitani K. , Morita Y. , Miura R. , Kanai S.
Published: April 2011

Choleresis induced by bucolome (BC) (1-cyclohexyl-5-n-butyl-2,4,6-trioxoperhydropyrimidine) was studied in male Wistar rats. [14C]Erythritol and mannitol clearance studies indicated this choleresis to be of canalicular origin. In 1-h continuous bile collection studies, immediately after the interruption of enterohepatic circulation (acute interruption), both bile flow and bile salt excretion rates were significantly increased in rats administered BC. However, the bile salt excretion rate fell rather rapidly in BC-administered rats, while the bile flow rate was fairly constant during this 1-h period. Thus, unlike the situation in control rats, bile flow rate was not significantly correlated with the bile salt excretion rate in BC-administered rats. In rats that had an external bile fistula open for 16–20 h (chronic interruption of enterohepatic circulation) the bile flow rate was also significantly increased by BC administration, while the bile salt excretion rate was not changed after BC administration.It is suggested that BC induced bile-salt-independent choleresis in both experimental rat groups (acute and chronic interruption of enterohepatic circulation). In addition, BC appeared to increase the bile-salt-dependent fraction of bile in rats with acute interruption of enterohepatic circulation, possibly by mobilizing the bile salt pooled in the intestinal content and (or) intestinal wall.
The effect of ouabain on the guinea pig ileum longitudinal smooth muscle: 1. ATPase activities in a sarcolemma-enriched fraction prepared with the aid of divalent cation depletion of the intact muscle
Authors: James M. R. , Roufogalis B. D.
Published: April 2011

Depletion of divalent cations before fractionation of the longitudinal muscle of the guinea pig ileum yielded a sarcolemma-enriched microsomal fraction free of mitochondria. A major portion of the ATPase activity in the presence of Mg, Na, and K was due to stimulation by Na alone. A further small stimulation by K was demonstrated only in the presence of an activating factor from the 105 000 × g supernatant. Ouabain inhibited only the K activation and had no effect on the Na-stimulated Mg-ATPase.
Pentobarbital sleeping time and waking blood levels in spontaneously hypertensive rats
Authors: Willis L. R. , Queener Sherry F.
Published: April 2011

Pentobarbital sleeping times and blood levels on arousal were determined in spontaneously hypertensive rats (SHR) and normotensive controls (WKR). Sleeping time for SHR was significantly less than for WKR, but blood levels of [14C]pentobarbital at awakening were not significantly different. The shorter sleeping time in SHR appears not to result from decreased brain sensitivity to pentobarbital. Instead, SHR appear to differ from WKR in the rate of metabolic clearance of the drug or in the distribution of the drug between blood and brain.
Isometric tension and instantaneous stiffness in amphibian skeletal muscle exposed to solutions of increased tonicity
Authors: Bressler Bernard H.
Published: April 2011

The instantaneous elasticity and maximum isometric tetanic tension of isolated frog and toad sartorii have been measured in hypertonic Ringer solution. Although the mechanical response of contracting muscle continued to decrease as the tonicity of the bathing solution was increased to 1.26 × R, 1.52 × R, and 2.04 × R, a similar change in the instantaneous stiffness could not be shown. This finding was not expected on the basis of our current model of the cross-bridge mechanism which predicts that the instantaneous stiffness is a measure of the total number of tension-generating cross-bridges formed in a stimulated muscle. The compatability of our findings with an electrostatic theory of the cross-bridge mechanism proposed by Iwazumi (1970) is discussed.
Presynaptic modulating effects of GABA on depression, facilitation, and posttetanic potentiation of a cholinergic synapse in Aplysia californica
Authors: Tremblay Jacques P. , Plourde Gilles
Published: April 2011

The effects of γ-aminobutyric acid (GABA) have been studied on the synaptic depression, frequency facilitation, and posttetanic potentiation (PTP) of a unitary, monosynaptic, and presumably cholinergic excitatory postsynaptic potential (EPSP). This EPSP, produced by minimal stimulation of the right visceropleural connective, was recorded in cell R15 of Aplysia californica.Perfusion with GABA (10−4–10−3 M) reduces the size of all EPSPs produced by a train of 100 stimuli at 1/s. It also reduces the synaptic depression and PTP, and increases the frequency facilitation seen during the train.GABA does not significantly affect the membrane resistance (mean 102%) but it slightly depolarizes (mean 6 mV) the postsynaptic cell. GABA does not reduce an acetylcholine iontophoretic potential produced on R15.The effects of GABA are reduced when chloride is replaced by acetate but they remain significant. Picrotoxin and bicuculline fail to antagonize GABA. Addition of sodium azide or dinitrophenol does not reduce the action of GABA and even prolongs it.The effects of GABA are attributed to two sites of action: a postsynaptic one, responsible for the small change in potential and partially responsible for the reduction of EPSP size; and a presynaptic one, responsible for a further reduction of EPSP size and the changes of depression, facilitation, and PTP.
The effect of hypertonic infusions on hepatic blood flows and liver volume in the cat
Authors: Lautt W. Wayne , MacLachlan T. Laurie , Brown L. Cheryle
Published: April 2011

The effects of intravenous and intraportal infusions of hypertonic NaCl and glucose solutions on the resistance and capacitance vessels of the intact feline liver were studied. All doses infused produced vasodilation of the hepatic artery. A rough estimate would suggest that the tonicity changes equal to those seen after hemorrhage might produce an increase of arterial conductance to no less than 110% and no greater than 140% of control conductance. In response to intravenous infusions, portal flow increased to the same extent as did arterial flows. The resistance vessels were equally affected by equal osmolal loads of glucose or NaCl but the hepatic volume changes were quite different depending on the substances infused. In marked contrast with the resistance vessel response to hypertonic NaCl, the hepatic capacitance vessels did not dilate. Liver volume decreased but whether due to mild capacitance stimulation or water egress from hepatocytes is not known. Cessation of the infusion resulted in increases of hepatic volume to above control levels. Glucose produced consistent steady increases in volume that may have been associated with fluid uptake by the hepatocytes in conjunction with glucose uptake.
Comparative effects of arachidonic acid, bisenoic prostaglandins, and an endoperoxide analog on the canine pulmonary vascular bed
Authors: Kadowitz Philip J. , Spannhake Ernst W. , Greenberg Stan , Feigen Larry P. , Hyman Albert L.
Published: April 2011

The effects of bolus injections of the postaglandin precursor, arachidonic acid, and PGD2, PGF2α, PGE2, and the PGH2 analog ((15S)-hydroxyl-9α,11α(epoxymethano)-prosta-5Z-dienoic acid) were compared on the pulmonary circulation in the intact spontaneously breathing pentobarbital-anesthetized dog. Arachidonic acid increased pulmonary arterial pressure, decreased aortic pressure, and increased cardiac output when injected into the superior vena cava or right atrium. PGE2, like arachidonic acid, increased pulmonary arterial pressure and cardiac output and decreased aortic pressure, whereas PGF2α and PGD2 increased pulmonary arterial pressure but did not affect cardiac output or aortic pressure when injected into the superior vena cava or right atrium. The PGH2 analog increased pulmonary arterial pressure and to a lesser extent, aortic pressure, without affecting cardiac output. None of these substances changed left atrial or right atrial pressure. The cardiopulmonary effects of arachidonic acid were blocked by indomethacin whereas the rise in pulmonary arterial pressure in response to the bisenoic prostaglandins and the analog were enhanced by the cyclooxygenase inhibitor. These data suggest that the increase in pulmonary vascular resistance in response to arachidonic acid may be due to conversion of the precursor into vasoactive intermediates and products such as bisenoic prostaglandins whereas the decrease in systemic vascular resistance is probably due to the formation of PGE2 and other peripheral vasodilator substances.
Neuronal depressant effects of diethylester derivatives of excitatory amino acids
Authors: MacDonald J. F. , Nistri A. , Padjen A. L.
Published: April 2011

The effect of iontophoretically applied kainic acid diethylester (KDEE) on the firing rate of feline spinal interneurones was investigated and compared with the action of glutamic acid diethylester (GDEE) and aspartic acid diethylester (ADEE). All these esters reversibly reduced spontaneous neuronal firing and increased spike height, KDEE being the most active of this group. KDEE decreased responses to glutamate, acetylcholine, and peripheral field stimulation, showing that its depressant action is not due to a selective antagonism of an excitatory putative transmitter.
Sodium intake following destruction of the anterior hypothalamus in the rat
Authors: Mercer P. F. , Mogenson G. J. , Paquette S. Y. M.
Published: April 2011

Sodium intake and sodium output were measured in rats before and after lesioning of the anterior hypothalamus. Both parameters were lower than control rats following the lesioning procedure. When an amount of sodium was given orally to these lesioned rats to make up the deficit in sodium intake, no difference was found in sodium intake or output between the rats with lesions and normal rats. Rats with anterior hypothalamic lesions were able to increase their sodium intake following a period of sodium deprivation or adrenalectomy. When presented with concentrations of sodium chloride ranging between 0.9 and 2.5%, rats with lesions decreased their intake of sodium in a manner similar to control rats except that the level of intake in the lesioned rats was lower for all concentrations. Control rats and those with lesions were not different in their intakes of KCl solutions. These findings suggest that the anterior hypothalamus is important in setting the absolute intakes of sodium but does not interfere with the control mechanisms regulating the sodium intake.
Reticuloendothelial system function and humoral factor deficiency following acute hemorrhage
Authors: Carr Freddie K. , Loegering Daniel J.
Published: April 2011

The present study has shown that following acute hemorrhage (equivalent to 3% body weight withdrawn over 20 min) in the rat, there is a large reduction (56% of control) in circulating α-2-glycoprotein opsonic activity. The reduction in this plasma opsonic activity was near maximal by the completion of blood withdrawal and was maintained throughout a 2-h hypotension period. There was no trend toward recovery of the opsonic activity when evaluated 15 min following reinfusion of shed blood in animals that were hypotensive for 0, 30, and 120 min. Reticuloendothelial system (RES) phagocytic function, as assessed from the carbon clearance rate (phagocytic index) following reinfusion of the shed blood, was depressed in animals that were hypotensive for 0, 30, and 120 min. Thus, phagocytic index followed a time course similar to the depression of opsonic activity. The observed close temporal relationship between α-2-glycoprotein opsonic deficiency and depression of RES clearance further supports the possible role of a humoral opsonic deficiency in mediating the RES phagocytic depression during circulatory shock.
The role of displacement of the mitral annulus in left atrial filling and emptying in the intact dog
Authors: Tsakiris Anastasios G. , Gordon Douglas A. , Padiyar Ramesh , Fréchette Diane , Labrosse Claude
Published: April 2011

The variations in ventricular–atrial mitral annular position during the cardiac cycle and the simultaneous changes in left atrial silhouette area (obtained by angiography after injections of contrast material into the main pulmonary artery) were investigated in six experiments on intact dogs with chronically implanted intracardiac markers. Frame-by-frame measurements of the angiograms (120 frames/s) were used to determine, under various hemodynamic conditions, the duration, magnitude, and average rate of the mitral annular motion and of the simultaneous changes in left atrial area during atrial filling (ventricular systole) and atrial emptying (early in ventricular diastole). The mitral annulus was seen to move towards the ventricular apex during systole and towards the atrium early in diastole with the duration, average rate, and magnitude of displacement (although varying widely) showing good statistical correlations (P < 0.0005–0.005) with the changes in projected left atrial area. These findings suggest that the duration, rate, and magnitude of atrial filling and emptying may be, in the intact heart, determined by the movements of the atrioventricular junction.
Hydraulic permeability coefficients of individual human erythrocytes
Authors: Jay Alfred W. L.
Published: April 2011

The hydraulic permeability coefficients of individual human erythrocytes were calculated from their rate of swelling to hemolysis as observed using microcinéphotography. Cells suspended in 10 mM Tris–HCl buffered Ringer solution (pH 7.40, 310 mosmol) were hemolyzed with hypotonic NaCl solutions ranging from 20 to 100 mosmol. The hemolysis, swelling, stress, potassium-leak, and hemoglobin-leak times all increased with increasing external impermeant concentration, but the relative magnitude of each stage of hemolysis remained unchanged. Of the total hemolysis time, swelling time only accounted for 20% while the stress time made up 80%. The stress time was further analyzed as potassium-leak and hemoglobin-leak times, which amounted to 22 and 58%, respectively. Permeability coefficients of individual erythrocytes ranged from 1.5 × 10−3 to 18.6 × 10−3 cm/s. The variation within a cell population represented a skewed normal distribution in each case of hemolysis by different solutions. The mean hydraulic permeability coefficient increased from 4.24 × 10−3 to 9.24 × 10−3 cm/s as external impermeant concentration decreased from 100 to 20 mosmol. Extrapolation of experimental data gave a value of 1.2 × 10−2 cm/s for water hemolysis at pH 7.40. This corresponds to a mean swelling time of 0.5 s. The permeability coefficient obtained with hemolysis by unbuffered (pH 6.0) distilled water gave a lower value of 7.34 × 10−3 cm/s. The discrepancy may be due to a possible effect of Tris on the cell membrane or it may be a result of a pH dependence of the membrane permeability coefficient. The dependence of mean hydraulic permeability on osmotic pressure has previously been explained as due to rectification of water flow across the cell membrane, but it may also be due to a dependence on membrane hydration and area changes in response to osmotic pressure as observed in a related study. The present study provides measurements of not only the mean hydraulic permeability coefficient for the red cell but also the range and distribution of permeabilities of individual cells within the cell population.
Mediation of isoproterenol-induced thirst in rats by β2-adrenergic receptors
Authors: Katovich M. J. , Fregly M. J.
Published: April 2011

Isoproterenol-induced thirst in rats has been attributed to the activation of β-adrenergic receptors. Since these receptors can be further differentiated pharmacologically into β1 and β2 types, experiments were performed using several β-adrenergic agonists and antagonists to determine the receptor type initiating the isoproterenol-induced thirst. The β1- and β2-adrenergic antagonist, d,l-propranolol (1 mg/kg, ip), blocked the increase in water intake usually accompanying acute subcutaneous administration of isoproterenol (25 μg/kg) to female rats. Since l-propranolol is known to stabilize membranes and to possess anesthetic-like properties, d-propranolol was also used. This isomer has little β-adrenergic-blocking activity but possesses anesthetic-like activity. Administration of d-propranolol (1 mg/kg, ip) failed to affect the drinking response to acute administration of isoproterenol (25 μg/kg). Practolol (125 mg/kg), a β1-adrenergic antagonist with little anesthetic properties, also had no effect on water intake of isoproterenol-treated rats. Butoxamine, a selective β2-adrenergic antagonist, attenuated the drinking response to isoproterenol. Salbutamol (150 μg/kg), a β2-adrenergic agonist, mimicked the effect of isoproterenol on water intake. These results are consistent with the suggestion that β2-adrenergic receptors mediate the isoproterenol-induced thirst in rats.
Transmucosal potential-difference profile in rat upper gastrointestinal tract. A simple model for testing gastric effects of pharmacologic agents
Authors: Tarnawski Andrzej , Ivey Kevin J.
Published: April 2011

Transmucosal potential difference in the rat upper gastrointestinal tract is described by a simple in vivo technique. Values for potential difference between blood (reference) and lumen (in millivolts) were the following: esophagus, −13.7 ± 1.6 (mean ± SE); forestomach (rumen), −39.2 ± 0.8; stomach fundus, −39.1 ± 0.4; pylorus, −26.6 ± 0.6; and duodenum, −9.2 ± 0.4. These values (excluding rumen) are strikingly similar to those obtained in man. Aspirin, taurocholic acid, and alcohol all produced falls in gastric potential difference very similar to those found in man. The rat appears to be a promising and convenient model for screening gastric effects of certain pharmacological agents before use in man.
Antagonism of substance P induced facilitation of central neuronal activity by 2,4-dinitrophenol and depressant agents
Authors: Sastry Bhagavatula R.
Published: April 2011

2,4-Dinitrophenol, pentobarbital, thiopental, methoxyflurane, and halothane more often antagonized the facilitatory effects of substance P than of acetylcholine on the activity of spinal dorsal horn neurons (of unanaesthetized decerebrated and spinalized cats) as well as interpeduncular and cerebral cortical cells (of either rats anaesthetized with methoxyflurane, nitrous oxide, and oxygen or 'cerveau isolé' rats). The results of the studies indicate that the excitatory effects of substance P on central neurons are extremely sensitive to anaesthesia.
Effect of estrogens on apomorphine-induced circling behavior in the rat
Authors: Bédard P. , Dankova J. , Boucher R. , Langelier P.
Published: April 2011

The effect of administration of estrogens parenterally for 1 week was tested on apomorphine-induced circling in a group of castrated female rats with a lesion of the left entopeduncular nucleus. We observed a significant decrease in the number of turns per minute in estrogen-treated animals as compared with controls. Our tentative explanation is that estrogens decrease the sensitivity of dopamine receptors in the striatum.
Adrenal-regeneration hypertension in Wistar–Furth rats
Authors: Hall C. E. , Nasseth D. , Hall O.
Published: April 2011

The susceptibility of young virgin female Wistar–Furth (W/Fu) rats to adrenal-regeneration hypertension (ARH) was evaluated by comparing the blood pressure of adrenal-enucleated, mononephroadrenalectomized, salt-loaded rats with that of similarly treated rats having one intact adrenal over a period of 5 weeks. Hypertension began to appear in animals of the first group by the 3rd week, affected all of them by the 4th week, and increased in severity during the 5th week. Control rats remained normotensive during the study. Hypertensive rats developed marked enlargement of the heart and kidney, which frequently displaced myocardial scarring and nephrosclerosis, respectively. These studies do not support the contention that W/Fu rats display heightened resistance to ARH to which, in fact, they appear to be just as susceptible as are most other strains.
Effects of simultaneous infusions of glucagon and cyclic AMP on glomerular filtration rate in the dog
Authors: Espinosa-Meléndez Enrique , Levy Mortimer
Published: April 2011

In this study, we tested the hypothesis that the renal vasodilator properties of glucagon are mediated by the intracellular release of cyclic AMP. In eight normal dogs, we tested the effect on glomerular filtration rate (GFR) of intravenous glucagon (5 μg/min), after having administered cyclic AMP (1.6 mg/min) into the left renal artery. GFR for both the right and left kidneys increased by 38% (p < 0.05), compared with an increment of 29% when glucagon alone had previously been administered. Similar studies were carried out in five dogs with steady-state hemorrhagic hypotension (arterial blood pressure = 75 mmHg). In this group as well, the prior infusion of cyclic AMP did not blunt or abolish the tendency of glucagon to promote renal perfusion or increase GFR. When cyclic AMP was administered alone, GFR and the clearance of p-aminohippurate usually declined by about 20% (p < 0.05). In six dogs, glucagon was administered intravenously at 5 μg/min prior to the infusion of cyclic AMP (1.6 mg/min) into the left renal artery. For this kidney, the anticipated decline in renal perfusion occurred. The prior administration of theophylline into the left renal artery did not prevent an intravenous infusion of glucagon from elevating GFR. These experiments indicate that the prior flooding of the microvasculature with either cyclic AMP or glucagon does not prevent the pharmacological effects of each of these substances. The renal hemodynamic effects of glucagon in normal and hypotensive dogs does not appear to depend on the release of cyclic AMP.
The rabbit mesenteric vein: a specific bioassay for substance P
Authors: Bérubé A. , Marceau F. , Drouin J. N. , Rioux F. , Regoli D.
Published: April 2011

The anterior mesenteric vein of the rabbit responds to substance P with dose-dependent contractions and is among the vascular smooth muscles most sensitive to this peptide. In spite of its high sensitivity to numerous other agents, including angiotensin and bradykinin, the rabbit mesenteric vein can be made selective for substance P by the use of specific inhibitors that will prevent the myotropic effects of acetylcholine, catecholamines, histamine, 5-hydroxytryptamine, and of the two above-mentioned peptides, without modifying the contractions elicited by substance P. It appears that this peptide acts directly on specific receptors and not through the release of neurotransmitters. Interference by intramural prostaglandins is excluded because substance P is equally active on tissues pretreated with indomethacin or untreated.Dose–response curves obtained with substance P are close to the theoretical curves predicted by the mass action law. The rabbit mesenteric vein contains a new type of receptor for bradykinin, recently identified (REGOLI, D., MARCEAU, F., and BARABÉ, J. 1978. De novo formation of vascular receptors for bradykinin. Can. J. Physiol. Pharmacol. 56, in press.). The action of bradykinin on this receptor can be prevented with the use of specific and competitive inhibitors and, therefore, the mesenteric vein will distinguish between peptides of the kinins or of the substance P types.
Methadone hydrochloride: effects of acute administration on disposition and hepatic function in guinea pigs
Authors: Pak R. C. K. , Ecobichon D. J.
Published: April 2011

d,l-Methadone hydrochloride (10 or 25 mg/kg body weight) was administered to adult female albino guinea pigs as either single doses or as daily doses for 6 consecutive days. A pharmacokinetic study was carried out on the animals receiving single doses, the plasma methadone being quantified by gas–liquid chromatography following solvent extraction. Different subgroups of animals receiving daily doses were killed after successive 24-h intervals for plasma and hepatic methadone residue analysis and for the in vitro measurement of hepatic monooxygenase (p-nitroanisole O-demethylase (OD); aniline hydroxylase (AH)) and glucuronyltransferase (GT) activities.No overt toxicity was observed at either dose administered. The β-phase plasma half-lives of the 10- and 25-mg/kg single doses were 13.2 and 13.8 h, respectively. Animals treated with six consecutive daily doses showed peak plasma and hepatic levels by day 2 of the treatment, followed by a gradual decline in subsequent days. The d,l-methadone did not significantly affect hepatic OD or AH though some reduction in activity was observed with the higher dose up to 7 days after stopping treatment. Significant reduction of GT activity was observed 24 h after the initial doses but, while the activities of animals receiving subsequent 10-mg/kg doses recovered, those of animals receiving 25-mg/kg doses remained significantly reduced even up to 7 days after treatment despite the fact that only traces of methadone could be detected in the livers.
Effect of hydrocortisone on phenylhydrazine-induced Heinz-body anemia
Authors: Jain S. K. , Chauhan V. P. S. , Mazumdar S. , Subrahmanyam D.
Published: April 2011

The effect of hydrocortisone on phenylhydrazine-induced anemia has been examined in adrenalectomized rats. The extent of hemolysis in adrenalectomized rats treated with phenylhydrazine was significantly higher than in normal and adrenalectomized rats supplemented with hydrocortisone.
Periodic, short-term heat exposure and reproductive function in male and female rats
Authors: Knecht Edwin A. , Wright Gary L. , Toraason Mark A.
Published: April 2011

Reproductive function of male and female rats was examined in relation to periodic, short-term heat treatment. Daily exposure to an environmental temperature of 38.2 °C for 55 min elevated rectal temperatures to 39.9 and 41.2 °C in male and female rats, respectively. Heat exposure tended to decrease copulation in males cohabitated with unhealed females. The rate of conception was affected similarly, and fetal survival tended to be reduced by paternal heat treatment. Estrous cycles were disrupted initially in heat-exposed females, but the rate of copulation and conception of females cohabitated with unheated males was unaltered by heat treatment. However, maternal heat exposure impaired prenatal survival and growth. During lactation, a high incidence of maternal and pup deaths was observed at approximately 14 days postpartum. Maternal deaths were coincident with a decrease in thermoregulatory ability and rectal temperatures exceeding 42 °C.
Labeling of a glucose binding protein in the rabbit intestinal brush border membrane
Authors: Lemaire J. , Maestracci D.
Published: April 2011

Using a double labeling method based on the method of Thomas (Thomas, L. 1973. Isolation of N-ethylmaleimide-labeled phloridzin-sensitive D-glucose binding protein of brash border membrane from rat kidney cortex. Biochim. Biophys. Acta, 291, 454–464.), with radioactive N-ethylmaleimide ([3H]NEM and [14C]NEM) in the presence and absence of D-glucose, a protein band which is periodic acid – Schiff staining insensitive and which has a relative mobility (Rm) of 0.55 (corresponding to a molecular weight of 51 000 daltons) as determined by sodium dodecyl sulfate (SDS) electrophoresis was labeled preferentially.When radioactive p-hydroxymercuriphenylsulfonate ([203Hg]PCMBS) is used in the presence and absence of D-glucose, as described by Smith et al. (SMITH, M. W., FERGUSON, D. R., and BURTON, K. A. 1975. Glucose- and phloridzin-protected thiol groups in pig intestinal brush border membranes. Biochern. J. 147, 617–619.), a protein band which has a relative mobility of 0.62 and a corresponding molecular weight of 42 000 daltons was labeled.Control experiments have shown that increasing concentrations of nonradioactive NEM (0.1–5.0 mM) do not substantially modify the electrophoretic pattern of SDS-solubilized brush border membrane. Nonradioactive PCMBS (0.1–10 mM), on the other hand, modifies the electrophoretic pattern and especially causes a change in relative mobility of the 0.55 protein band which migrates after 1 mM PCMBS treatment with a Rm of 0.62.The effect of 1 mM PCMBS can be reversed by adding L-cysteine or dithiotreitol.Actin extracted from rabbit muscle migrates with the same Rm as the 0.55 protein band in our electrophoretic conditions.
The electromyographic response to sudden stretches of limb muscles in normal human subjects
Authors: O'Riain M. D. , Blair R. D. G. , Murphy J. T.
Published: April 2011

The electromyographic (EMG) activity following a sudden stretch applied to wrist flexor or extensor muscles was investigated using a method which enabled the individual records and cumulative results of 30 trials to be observed simultaneously. The results showed that in each case the spinal reflex EMG burst was followed by one or two additional reflex bursts. The second of these latter bursts, when present, occurred in one of two distinct latency ranges. Thus, three distinct latency ranges were observed for reflex bursts following the spinal reflex burst. A possible explanation for these results is that there are three distinct long-loop reflexes, one or two of which may be active following a muscle stretch. The present results do not distinguish whether any or all of these long-loop reflexes are segmental or supraspinal in origin.
Intracellular actions of monoamine transmitters
Authors: Krnjević K. , Lamour Y. , MacDonald J. F. , Nistri A.
Published: April 2011

Intracellular injections of noradrenaline or dopamine in spinal motoneurones of cats have a clear depolarizing action associated with particularly marked depression of spike potentials and their after-hyperpolarization, but with little slowing-down of the falling phase of the action potential. These effects are associated with an increase in input resistance, and they are reversible and reproducible in the same neurone. Intracellular injections of 5-hydroxytryptamine have some depolarizing action and increased input resistance, but they produced no comparable depression of the action potential and tended to enhance the after-potentials and increase excitability. It is concluded that changes in intracellular levels of monoamines, whether physiological or drug induced, may be of significance for central neuronal function.
The effects of acetylcholine and atropine on the 22Na+ permeability of intestinal smooth muscle vesicles
Authors: Spero L.
Published: April 2011

A technique is described which has enabled us to measure changes in 22Na+ efflux from smooth muscle plasma membrane vesicles. The resting 22Na+ efflux from these sealed vesicles showed a concentration-dependent increase in response to acetylcholine and other muscarinic agonists, in similar concentrations to those which increased 42K+ efflux in whole muscle. The kinetics of this efflux were complex and could not be described by less than three exponential processes. The response to agonists has, therefore, been characterized by measurement of the half-life of 22Na+ efflux (t1/2). The acetylcholine effect was inhibited by atropine, but unlike the situation in the whole muscle, this inhibition was noncompetitive. Tubocuraine (a nicotinic antagonist) had no effect on this acetylcholine response. Atropine has no effect by itself on the resting 22Na+ efflux, neither did tetrodotoxin or ouabain. 22Na+ efflux from erythrocyte ghosts and liposomes, prepared from lipid extracts of the smooth muscle plasma membrane, was not modified by acetylcholine or atropine.