bluuebunny/crossref_metadata_2025 huggingface dataset:
Action of Angiotensin and Analogues on the Heart
Authors: Bonnardeaux J. L. , Regoli D.
Published: April 2011

The action of angiotensin II (ATII) and of several analogues, including antagonists, has been studied on isolated perfused rabbit hearts. Changes of transmembrane potential have been recorded from atrial and ventricular fibers with floating microelectrodes.ATII, heptapeptide (2–8), and 1-Sar-ATII increase the amplitude of contraction and prolong the P–R interval of the electrocardiogram. High doses of ATII and heptapeptide (2–8), but not of 1-Sar-ATII, decrease heart rate. Inhibitory analogues (8-Gly-ATII, 1-Sar,8-Gly-ATII) are inactive on tension but prolong slightly the P–R interval.The plateau phase of the action potential (A.P.) in atrial fibers is significantly prolonged by ATII, heptapeptide (2–8) and 1-Sar-ATII, while antagonists do not produce any change. The plateau phase of ventricular cells is similarly prolonged by ATII and heptapeptide (2–8); the other analogues were not tested.Hearts taken from reserpinized rabbits respond to ATII and heptapeptide (2–8) with similar changes of tension and transmembrane potential as the hearts of non-treated rabbits.The effects of ATII and heptapeptide (2–8) are inhibited by relatively small doses of 8-Gly-ATII and 1-Sar,8-Gly-ATII; inhibition by 8-Gly-ATII is surmountable with ATII.The results indicate that (a) ATII and heptapeptide (2–8) have a direct effect on the myocardium, (b) this effect is antagonized by position 8 substituted analogues of ATII that inhibit the action of ATII on smooth muscles and in vivo, and (c) changes of tension of myocardial fibers are accompanied by an increased duration of A.P. plateau phase.
L-DOPA–Chlorpromazine Antagonism on Running Activity in Mice
Authors: Derkach Peter , Larochelle Louis , Bieger Detlef , Hornykiewicz Oleh
Published: April 2011

An attempt was made to study the nature of the antagonistic effect of chlorpromazine on running activity induced by L-3, 4-dihydroxyphenylalanine (L-DOPA) in mice. Dose–effect relations for L-DOPA, given alone and in combination with chlorpromazine, were determined in male albino mice pretreated with an inhibitor of the extracerebral aromatic L-amino acid decarboxylase. Chlorpromazine produced a marked depression in the maximal running response to L-DOPA and a flattening in the slope of the L-DOPA dose–response curve. The results are compatible with a noncompetitive blockade of central dopamine receptors by chlorpromazine as the main mechanism of the drug's anti-L-DOPA activity.
Plasma Renin Activity During the Natriuretic Response to Preoptic Lesions in Rats
Authors: Keeler R. , Hawkins T. L.
Published: April 2011

Plasma renin activity (PRA) was assayed during the natriuretic response to bilateral lesions in the preoptic area of the rat hypothalamus.In operated animals PRA was significantly lower than in normal rats but was not significantly different from PRA in sham-operated controls.It was concluded that preoptic lesions did not cause specific changes in PRA and that changes in PRA did not account for the natriuretic response.
Effect of Hemorrhagic Shock on Tissue Adenine Nucleotides in Conscious Rats
Authors: Chaudry Irshad H. , Sayeed Mohammed M. , Baue Arthur E.
Published: April 2011

Hemorrhagic shock was produced in conscious rats by cannulating the subclavian artery and bleeding the animals to a mean arterial pressure of 40 mm Hg which was maintained for 1 (early shock) or 2 h (late shock). Analysis of tissues showed that there was a significant decrease in ATP and ADP levels in liver and kidney in early and late shock. Associated with the decrease in ATP and ADP levels were increases in AMP and P1 levels. In contrast to the above organs, adenine nucleotides and creatine phosphate levels of skeletal muscle did not decrease in early shock but a significant reduction of these compounds was observed in late shock. The decrease in ATP content was greater in liver and kidney than in skeletal muscle. The present experiments indicate that there is a decrease in the energy available to tissues during severe hemorrhagic shock. This could be due to decreased biosynthesis, to continuing or increased utilization of the nucleotides, or to both.
Preferential "Binding" of γ-Aminobutyric Acid and Glycine to Synaptosome-Enriched Fractions of Rat Cerebral Cortex and Spinal Cord
Authors: Defeudis F. V.
Published: April 2011

The "binding" activities of 3H-γ-aminobutyric acid (3H-GABA) and 14C-glycine in synaptosome-enriched factions of rat cerebral cortex and spinal cord have been compared in an isosmotic sucrose medium (containing 32 mM NaCl) over a wide range of concentrations using differential centrifugation and a double-isotope method. It was shown that GABA was bound preferentially to particles of cerebral cortex whereas glycine "binding" occurred preferentially to those of spinal cord. At equimolar concentrations of 3H-GABA and 14C-glycine in the medium (0.8 × 10−7 M – 0.8 × 10−4 M) the order of potency of "binding" was as follows: GABA, cortex > GABA, cord [Formula: see text] glycine, cord > glycine, cortex. Ratios of GABA/glycine were always much greater than 1.0 for cerebral cortex when these amino acids were present in the medium at 10 −7–10−4 M, whereas these ratios were about 1.0 for spinal cord at all concentrations of the amino acids that were used. The "maximal binding capacity" (Bmax) for GABA, at 0 °C, was estimated to be about 65 nmol of GABA/g cortex, and its "binding" constant (KB) was about 1.8 × 10−5M. For the "binding" of glycine to fractions of spinal cord at 0 °C, the respective values for Bmax and KB were 43 nmol of glycine/g, cord, and 3.3 × 10−5 M. It is suggested that these energy-independent "binding" mechanisms may be involved in the inactivation and receptor interactions of these "active" amino acids.
Projection of Primary Muscle Spindle Afferents to Motorsensory Cortex
Authors: Wong Y. C. , Kwan H. C. , Murphy J. T.
Published: April 2011

Rhomboidal stretches of low amplitude and velocity were applied to extensor digitorum communis muscle in regionally anesthetized cats. These inputs, which selectively activate primary muscle spindles, were found to excite neurons in a restricted region of contralateral motorsensory cortex. This same region was determined to be 'motor cortex' for this muscle on the basis of evidence from both cyto-architectonic and intracortical microstimulation studies. This functional loop may be important for transcortical reflexes.
Mechanism of the Effect of Acetate on Frog Ventricular Muscle
Authors: Anderson Esther R. , Foulks J. G.
Published: April 2011

Substitution of acetate for external Cl produced a large persistent increase in the resting membrane potential (R.M.P.) of frog ventricle and a somewhat steeper relation between membrane potential (M.P.) and [K]o (external K concentration). An increased K conductance or reduced permeability to other ions could account for most of these results, but not for hyperpolarizations as great as −110 mV. Potentials of this size suggested a contribution from an active electrogenic transport system, but they were unaffected by several treatments including exposure to ouabain (10−7 M − 5 × 10−6 M), dinitrophenol (10−6 M, 10−5 M) or 30 mM tetraethylammonium.Acetate caused a prolongation of the action potential (A.P.) and a change in its configuration. Acetate also enhanced twitch tension and increased the rate of tension development. Similar changes are produced by removal of [K]o. The effects of both acetate and K removal on A.P. configuration were prevented by a reduced rate of stimulation.When acetate-induced hyperpolarization was reversed by raising [K]o to 10–15 mM, the configuration of the A.P. resembled that of controls and twitch tension did not increase. Thus, acetate-induced changes in the shape of the A.P. and in twitch tension appeared to be secondary to the increase in R.M.P. However, the relationship does not seem to be direct because these changes were temporary, whereas hyperpolarization was persistent.The character of the acetate-induced changes in A.P. configuration, and the dependence on stimulation rate and [Ca]o (external Ca concentration), suggested a raised [Ca]i (internal Ca concentration) and a possible increase in Ca influx. However, addition of Mn to the acetate solution did not prevent initial acetate-induced changes in the shape of the A.P. plateau and in twitch tension. Also in the absence of [Ca]o, disappearance of twitch tension was slowed by acetate. But acetate decreased the contracture tension produced in response to either increased [K]o or Na removal. Acetate may cause a redistribution of Ca within the cell.
Some Characteristics of Corticosterone Uptake by the Dorsal Hippocampus and the Adenohypophysis in the Rat
Authors: Lemaire Irma , Dupont André , Bastarache Edouard , Labrie Fernand , Fortier Claude
Published: April 2011

In addition to confirming the reports by McEwen and co-workers of a selective uptake of corticosterone by the dorsal hippocampus in adrenalectomized rats, our findings have brought to light an inverse relationship between corticosterone retention by the hippocampus and its binding by plasma transcortin, 4 days after adrenalectomy, which raises the possibility of a competition between extracellular and intracellular binding sites for corticosterone.A subsequent study of the uptake characteristics of the 30 000 × g pellet and supernatant of the dorsal hippocampus, the cerebral cortex, and the adenohypophysis, under conditions of dynamic equilibrium between corticosterone and its binding sites achieved by perfusing at a constant rate graded concentrations of the steroid, has yielded evidence for the selective uptake of corticosterone by both the particulate (chiefly nuclei and mitochondria) and the soluble (cytosol) fractions of the dorsal hippocampus and of the adenohypophysis, the hippocampus showing a greater uptake capacity than the hypophysis. The observed saturation of the sites of the dorsal hippocampus and of the adenohypophysis at physiological concentrations of plasma corticosterone is consistent with the involvement of these two structures in the feedback control of adrenocorticotropin secretion by circulating corticosteroids.
Effects of Guanethidine and Imidazole on Histamine Response
Authors: LeBlanc J. , Côté J. , Doré F.
Published: April 2011

Guanethidine was shown to increase sensitivity (as measured by blood pressure response) not only to noradrenaline but to acetylcholine and histamine (H) as well. This effect of guanethidine on H is not likely explained by lack of reflex sympathetic activity resulting from chronic treatment but possibly by a reduced uptake of H. Similarly, chronic treatment with guanethidine, by increasing H release, could have increased tolerance to H, thus explaining some of the results obtained. This is not the case since chronic treatment with H was shown to increase rather than decrease response to H in the rat. Imidazole, which was also shown to increase histaminuria (Can. J. Physiol. Pharmacol. 50, 539–544, 1972), did not potentiate H, noradrenaline, or acetylcholine response and possesses some slight antihistaminic effect. Finally noradrenaline blocks the effect of guanethidine on release of H but has no effect on the action of imidazole.
Fluoride Nephropathy: Lack of Direct Involvement of Renal ATPase
Authors: Tobin Thomas , Akera Tai , Dworin Jeffrey Z. , Brody Theodore M.
Published: April 2011

A dose-related fluoride- or methoxyflurane-dependent nephropathy has been demonstrated in Fisher 344 rats, which appears related to methoxyflurane nephropathy in man. Since the fluoride ion inhibits Na++K4 ATPase, the possibility of direct involvement of renal ATPase in this syndrome was investigated. Fluoride inhibited rat kidney Na++K4 ATPase in vitro in the presence of Na+ and ATP and the inhibition produced in this way was stable under conditions used for preparation of this enzyme. However, when sodium fluoride was given subcutaneously to Fisher 344 rats their urinary output increased fivefold without any significant changes in renal Na++K4-ATPase or Mg2+-ATPase activity. These results appear to rule out a direct irreversible action of fluoride on renal Na++K4-ATPase or Mg2+-ATPase activity as a mechanism of fluoride or methoxyflurane nephropathy. An indirect action of fluoride on Na+ transport by limiting the supply of glycolytic energy to the pump remains likely.
Calcium Reversal of Nerve Blockade by Alcohols, Anesthetics, Tranquilizers, and Barbiturates
Authors: Seeman P. , Chen S. S. , Chau-Wong M. , Staiman A.
Published: April 2011

This study shows that Ca2+ reversed the nerve-blocking actions of procaine, lidocaine, procainamide, imipramine, chlorpromazine, tetrodotoxin, hexanol, heptanol, benzyl alcohol, thymol, sodium barbital, and sodium pentobarbital. Using the rat phrenic nerve, it was found that an elevation of external Ca2+ (from 0.22 mM to 4.4 mM) restored the blocked compound action potential of the nerve by around 30% for all three types of drugs: cationic, anionic, and uncharged.The high Ca2+ level of 4.4 mM displaced chlorpromazine from brain synaptosome membranes, but did not displace heptanol, pentobarbital, or lidocaine. Since there was no relation between blockade reversal and drug displacement by Ca2+, the data do not support the idea that Ca2+ and drugs compete for membrane-binding sites. Since approximately the same magnitude of reversal occurred with different drugs, as well as with tetrodotoxin, it is concluded that Ca2+ may cause a physiological kind of allosteric antagonism of the drug-blocked Na+ channel, or a direct augmentation of the Na+ conductance.
Glutamate Dehydrogenase, Glutamic Acid Decarboxylase, and GABA Amino Transferase in Epileptic Mouse Cortex
Authors: Gelder N. M. van
Published: April 2011

Determinations of glutamate dehydrogenase (GDH), glutamic acid decarboxylase (GAD), and GABA aminotransferase (GABA-T) in the epileptogenic (cobalt) mouse cortex revealed a fall in the activities of GDH and GABA-T and an increase in GAD. However, of the three enzymes, only changes in GDH appeared to coincide with the entire period that animals were epileptic. The decrease in GABA-T was observed in the first week following the onset of cobalt-induced epilepsy but the activity of this enzyme had returned to normal before all epileptic signs had disappeared. On the other hand, the rise in GAD activity was observed 3–4 days after epilepsy had become established. Injections of taurine to animals did not influence the above findings but might have slowed recovery to normal enzyme values.
Negative Cardiac Inotropic Effects of Calcium Ion and of N-2-Hydroxyethylpiperazine-N′-2-ethanesulfonic Acid (HEPES) Buffer at Normal and Low Sodium Concentration
Authors: Dresel Peter E.
Published: April 2011

Isolated electrically driven left atria from rabbits were suspended in N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES) buffer and exposed to increasing concentration of calcium ions in the presence of different concentrations of sodium. Maximal contractile force occurred at 10 mM Ca and 145 mM Na. Higher concentrations of Ca had a negative inotropic effect. Lowering the Na concentration decreases the concentration of Ca required to observe the negative inotropy, until at 60–70 mM Na, it occurred at 5 mM Ca. This last result was confirmed in Krebs–Henseleit solution. Contractility at low Na and/or Ca media was less in HEPES than in Krebs buffer.
Theophylline Inhibition of Nucleoside Transport and its Relation to Cyclic AMP in Skeletal Muscle
Authors: Woo Yin-Tak , Manery J. F. , Dryden E. E.
Published: April 2011

Using [14C]inosine and [3H]sorbitol, the effect of theophylline on inosine uptake was studied. Theophylline inhibited the intracellular uptake of inosine by isolated, frog skeletal muscle in a dose-dependent way. An inhibitory effect was also observed for the uptake of labelled adenosine, uridine, hypoxanthine, and adenine, but not for ribose. The inhibition was not readily reversible and was noncompetitive in nature. It was not secondary to the contracture of the muscle produced by the drug, because various treatments known to cause contracture had no effect on inosine transport. Also, papaverine (0.3 mM) significantly inhibited inosine transport without affecting the contractile properties of the muscle. Although theophylline is a cyclic AMP phosphodiesterase inhibitor, no relation could be found between inhibition of inosine uptake and cyclic AMP. N8,O2′-Dibutyryl cyclic AMP (1 mM) was ineffective. Though isoproterenol (10 μg/ml) increased the cyclic AMP concentrations in the muscle by 26-fold in the presence of theophylline and 3-fold in the absence of the drug, it did not influence inosine transport. Tracing the label into various intracellular nucleotides after incubation of the muscle with [14C]inosine suggested that theophylline inhibited inosine transport rather than inosine metabolism.
The Effect of Combined Hypocapnia and Hypoxemia upon the Energy Metabolism of the Brain
Authors: MacMillan V.
Published: April 2011

To evaluate whether hypocapnia affects the energy metabolism of the hypoxic brain, lightly anesthetized rats were maintained for 30 min at a [Formula: see text] of close to 30 mm Hg (1 mm Hg = 133 N/m2) and at [Formula: see text]'s of close to 35, 25, and 18 mm Hg, and compared with normoxic rats maintained at equivalent [Formula: see text]. The results showed that in hypoxic rats the energy state of the tissue, as evaluated from the adenylate contents and energy charge of the adenine nucleotide system, was adversely affected by exposures to [Formula: see text] of 18 mm Hg. The hypocapnia increased the accumulation of lactate during hypoxemia without altering the lactate/pyruvate ratio. Examination of the tissue levels of carbohydrate substrates, cerebral venous [Formula: see text], derived intracellular pH, and cytoplasmic NAD+/NADH ratios did not indicate that the increased tissue lactate accumulation was due to a further defect in tissue oxygenation. It is concluded that hypocapnia during hypoxemia is potentially detrimental.
Phosphate-Transport Appearance in the Sea-Urchin Egg. I. Effects of Protein-Synthesis Inhibitors on Fertilized Eggs and Embryos
Authors: Noüe Joël de la
Published: April 2011

When fertilized eggs of Strongylocentrotus purpuratus, the purple sea urchin, are incubated in sea water containing 32PO43− and L-14C-valine, valine incorporation is inhibited in the presence of puromycin, cycloheximide, or chloramphenicol, but only the last inhibits the active transport of phosphate. Since chloramphenicol does not depress the egg respiration, it is likely that this drug acts specifically. This is in line with a lack of inhibitory effect of chloramphenicol on phosphate uptake at later developmental stages, except at the time of gastrulation, when the appearance of new phosphate carriers might well occur. It is suggested that the active transport carrier for phosphate, or some element required for its operation, is synthesized after fertilization, with the likely participation of the mitochondrial protein-synthesis machinery. A similar proposal holds for valine uptake.
Investigation of a Possible Interaction between Propranolol and a Nitrite on Coronary Artery Tone
Authors: Kalsner Stanley
Published: April 2011

The left circumflex coronary artery of the beef heart, in a state of tone induced by potassium, relaxed in response to sodium nitrite (1 μM–100 mM). The beta adrenergic antagonist propranolol (1 or 10 μM) had no detectable effect on the nitrite dose–response curve. In addition, propranolol did not alter directly the tone of the partially constricted coronary artery.
Effect of Glucagon on Radiocalcium Excretion by the Colon in Rats after Intracardial Administration of 45Ca
Authors: Bogdał J. , Jędrychowski A. , Tarnawski A. , Dura K. , Marszałek Z.
Published: April 2011

After intramuscular administration of glucagon to rats that previously had received 45Ca intracardially, the radioactivity of the colonic fecal content was tenfold lower than that of controls and the radioactivity of the colonic wall was increased moderately.
The Effect of Age on Arterial–Alveolar Nitrogen Difference in Normal Adults
Authors: Corbet A. J. S. , Ross J. A. , Beaudry P. H.
Published: April 2011

The arterio-alveolar nitrogen difference [Formula: see text] has been assessed in 27 normal adult subjects aged 20–60 years. As it may be assumed that venous and arterial [Formula: see text] are identical, we have used a sample of venous blood. There is a significant positive correlation between [Formula: see text] and age. As the increase of [Formula: see text] with age resembles that found in the literature for [Formula: see text], we conclude that the latter may be explained by increasing[Formula: see text] inequality within the lung.
Intestinal Calcium-Binding Protein in Animals Fed Normal and Rachitogenic Diets: II Pig Studies
Authors: Harrison Joan E. , Hitchman A. J. W. , Brown R. G.
Published: April 2011

Experiments were carried out in pigs to investigate the relationship between concentrations of intestinal calcium-binding protein (CaBP) and the presence of rickets. Pigs made rachitic by a diet deficient in calcium and in vitamin D had concentrations of intestinal CaBP no less than values obtained on control pigs. These experiments, together with earlier work on rats (Can. J. Physiol. Pharmacol. 1975. 53, 137–143), demonstrate a poor inverse correlation between levels of intestinal CaBP and rickets.
Some Pharmacological Effects of Prodolic Acid, a New Anti-inflammatory Compound, Indicative of Inhibition of Prostaglandin Synthesis
Authors: Greenberg R.
Published: April 2011

Prodolic acid, a new non-steroidal anti-inflammatory compound, inhibited bradykinin-induced bronchoconstriction but did not affect histamine-induced bronchoconstriction in the guinea pig. Prodolic acid potentiated the responses of the isolated rabbit vas deferens and portal vein to electrical stimulation without altering the response to noradrenaline. The potentiating effects of prodolic acid on the vas deferens were reversible but the potentiating effects in the portal vein were frequency-dependent. It is concluded that these effects of prodolic acid are probably related to its ability to inhibit prostaglandin biosynthesis.
Divergent Effects of Excess Dietary Vitamin A on Alimentary Cholesterolemia in Cockerels of Different Genetic Backgrounds
Authors: Woodward Bill , March B. E.
Published: April 2011

The variable effect of excessive vitamin A intake on alimentary cholesterolemia was investigated in cockerels of strains of White Leghorns and New Hampshires. With the New Hampshire cockerels, the feeding of 0.5% of dietary cholesterol resulted in greater cholesterolemia when the diet contained 1 700 I.U. of vitamin A per kilogram than when it contained 22 000 I.U. of vitamin A per kilogram. With the White Leghorn cockerels, on the other hand, cholesterolemia was enhanced with the higher level of dietary vitamin A. Absorption of a single oral dose of cholesterol was increased in birds of both breeds when vitamin A had been given previously by injection. In the White Leghorn cockerels the percentage of newly absorbed cholesterol in the hepatic pool was reduced by vitamin A administration, whereas in the New Hampshire cockerels the percentage was increased. It was concluded that excess vitamin A may have divergent effects on alimentary cholesterolemia in chickens of different genetic backgrounds as a result of opposite effects on the liver–blood ratio of a large load of cholesterol.
Thermal, Metabolic, and Cardiovascular Responses to Various Degrees of Cold Stress
Authors: Raven Peter B. , Wilkerson James E. , Horvath Steven M. , Bolduan Nils W.
Published: April 2011

The metabolic, thermal, and cardiovascular responses of two male Caucasians to a 2 h exposure to ambient temperatures ranging between 28 °C and 5 °C were studied and related to the respective ambient temperatures. The metabolic heat production increased linearly with decreasing ambient temperature, where heat production (kcal∙m−2∙h−1) = −2.79 Ta °C + 103.4, r = −0.97, P < 0.001. During all exposures below 28 °C, the rate of decrease in mean skin temperature [Formula: see text] was found to be an exponential function dependent upon the ambient temperature (Ta) and the time of exposure. Reestablishment of [Formula: see text] steady state occurred at 90–120 min of exposure, and the time needed to attain steady state was linearly related to decreasing Ta. The net result was that a constant ratio of 1.5 of the external thermal gradient to the internal thermal gradient was obtained, and at all experimental temperatures, the whole body heat transfer coefficient remained constant. Cardiac output was inversely related to decreasing Ta, where cardiac output [Formula: see text], r = −0.92, P < 0.01. However, the primary reason for the increased [Formula: see text], the stroke output, was also described as a third-order polynomial, although the increasing stroke volume throughout the Ta range (28–5 °C) was linearly related to decreasing ambients. The nonlinear response of this parameter which occurred at 20 °C ≥ Ta ≥ 10 °C suggested that the organism's cardiac output response was an integration of the depressed heart rate response and the increasing stroke output at these temperatures.
Application of Drug Receptor Theories to the Analysis of the Myotropic Effects of Bradykinin
Authors: Barabé J. , Park W. K. , Regoli D.
Published: April 2011

Cat jejunum and terminal ileum, and rat stomach strip and rat uterus contract to bradykinin, while rat duodenum relaxes. Dose–response curves of classical hyperbolic shape are obtained in the first three preparations, but not in the others.The negative logs of the drug concentrations which give 50% of the maximal response. (pD2) values were, respectively, 7.68 and 7.77 in the cat jejunum and terminal ileum, 6.78 in the rat stomach strip and 8.64 in the rat uterus in estrus.Theoretical dose–response curves, constructed by using experimental pD2 values in the equation of Clark, (General pharmacology. Verlag Van J. Springer, Berlin, 1937), are superimposed to experimental curves, obtained in the cat jejunum and terminal ileum, but not in the rat stomach strip. This comparison was not made in the rat uterus and duodenum.The myotropic effect of bradykinin appears to be a direct one in the cat jejunum, the terminal ileum and the rat stomach strip, because it is not affected by anticholinergics, antiadrenergics, antihistaminics and indomethacin. pD2 values and the slope of the dose–response curves of the rat uterus were reduced by indomethacin.The results indicate that cat jejunum and terminal ileum are sensitive and specific for bradykinin and appear to be the most reliable preparations for studies on the structure–activity relationships of this peptide.
Isoosmotic Transport of Fluid Across the Hamster Small Intestine in the Presence of Phlorizin-Induced Inhibition of Sugar Transport
Authors: Dinda P. K. , Beck Marjorie , Beck Ivan T.
Published: April 2011

Experiments were performed to investigate whether the fluid transported across the small intestine is isoosmotic with the mucosal solution when the active transport of glucose is partially inhibited. Everted hamster mid small intestine was incubated in one of the following four mucosal solutions: (1) Isotonic control, Krebs–Ringer bicarbonate solution containing 10 mM glucose (KRBSG); (2) Isotonic with phlorizin, KRBSG + 5 × 10−5 M phlorizin; (3) Hypertonic control, KRBSG + 50 mM mannitol; (4) Hypertonic with phlorizin, KRBSG + 50 mM mannitol + 5 × 10−5 M phlorizin. The serosal surface of the intestine was not bathed. Results indicate that the transported fluid was always isoosmotic with any of the mucosal solutions used. When the mucosal solution was made hypertonic with mannitol, the concentration of glucose and electrolytes in the absorbate increased, and as a result, the absorbate became hypertonic and isoosmotic with the mucosal solution. The presence of phlorizin either in the isotonic or in the hypertonic mucosal solution decreased the glucose concentration of the absorbate, but the transported fluid became isoosmotic with the mucosal solution due to a higher concentration of Na, K, and their associated anions. Phlorizin caused a decrease in the transmural potential difference. In spite of this, the presence of this glucoside in the mucosal solution increased the transport of sodium in relation to glucose transport. It is suggested that, at the concentrations used, phlorizin inhibits sodium movement through the electrogenic pathway, but increases the transport of this ion through the non-electrogenic route. This increase in neutral sodium transport seems to compensate for the low concentration of glucose in the absorbate, so that the absorbate becomes isoosmotic with the mucosal solution whether the latter is isotonic or hypertonic. It is suggested further that isoosmotic transport of fluid is an inherent property of the small intestine and that there may be an osmoregulatory mechanism in the gut which controls this process.
Role of the C-terminal Group for the Biological Activities of Angiotensin
Authors: Rioux F. , Park W. K. , Regoli D.
Published: April 2011

The C-terminal group of angiotensin II (ATII), 1-Sar-ATII, and 1-β-Asp-ATII was esterified to reduce degradation of the peptides by carboxypeptidases.Biological activity of esterified angiotensins was measured in vivo (rat blood pressure) and in vitro (rabbit aorta strip). Degradation in vitro by purified carboxypeptidase was estimated from the intensity of the phenylalanine spot on paper chromatography. Disposition of esterified angiotensins by rabbit aorta strips was studied with the oil immersion technique of Kalsner and Nickerson, Can. J. Physiol. Pharmacol. 46, 719–730, (1968a).The results indicate that esterification of C-terminal group of ATII: (a) reduces the potency in vivo and to a greater extent the affinity in vitro; (b) delays the onset of the contraction in vitro; (c) does not affect the intrinsic activity; (d) prolongs the time of relaxation of rabbit aorta strips in oil; (e) prevents the degradation by purified carboxypeptidase.It is proposed that C-terminal group of ATII contributes to affinity but not to intrinsic activity and facilitates the diffusion of the peptide to receptor sites. Esterification of this group prevents the degradation of the peptide by carboxypeptidases; accordingly, the duration of action in vivo is prolonged and the rate of relaxation of aortic strips in oil is reduced. When esterification of the C-terminal is combined with the replacement of Asp by β-Asp in position 1, no relaxation of aortic strips occurs after oil immersion. This suggests that carboxypeptidases, and to a minor extent aminopeptidases, are responsible for the inactivation of angiotensin by rabbit aorta.
Pentobarbital Inhibits the Biliary Excretion of Organic Acids: a Study with Succinylsulfathiazole in the Rat
Authors: Bailey D. G. , Paul H. , Johnson G. E.
Published: April 2011

The present study was undertaken to determine whether the use of pentobarbital as an anesthetic reduces the biliary excretion of acidic drugs in rats. The drug chosen for the experiment was succinylsulfathiazole, a compound excreted unmetabolized in the bile. Animals anesthetized with urethane excreted 22.1% of the dose in the bile as compared to only 8.4% for the same time period in pentobarbital anesthetized animals. The choice of anesthetic did not affect the bile flow but did influence the bile/liver concentration gradient of succinylsulfathiazole, with the pentobarbital treated rats demonstrating a significantly lower value. Despite the higher biliary excretion of succinylsulfathiazole in the urethane treated rats, the total amount in the bile plus urine was 60% of the dose in the urethane anesthetized animals as compared with 62% in the pentobarbital treated rats. These results suggest that pentobarbital reduced the hepatic transport of succinylsulfathiazole into the bile. The question whether urethane is a preferred anesthetic for biliary excretion studies warrants further investigation.
Feedback Inhibition of Adrenocorticotropin Release by Corticosterone Infusions in the Adrenalectomized Rat
Authors: Rotsztejn William , Lalonde Josée , Normand Maurice , Fortier Claude
Published: April 2011

Advantage was taken of a specific and sensitive bioassay for rat plasma adrenocorticotropin (ACTH) based on the dispersion of rat adrenal cells with trypsin, to investigate the relationship between plasma corticosterone concentration and inhibition of ACTH release under steady-stale conditions achieved by graded rates (0–5.12 μg/min per 100 g body weight) of intravenous infusion of the steroid for 45 min in 28-day adrenalectomized rats. In contrast to prior reports involving suppression of stress-induced ACTH release, the inhibitory effect of corticosterone was shown, under our experimental conditions, to be exerted also on the basal rate of ACTH secretion. Indeed, a slight though not significant decrease of plasma ACTH concentration was observed with the corticosterone infusion rate of 0.64 μg/min per 100 g body weight, and further progressive and highly significant drops in concentration were recorded for infusion rates of 2.56 and 5.12 μg/min per 100 g body weight. An increase of the metabolic clearance rate of corticosterone, observed as a function of the infusion rate, was ascribed to saturation by the steroid of the plasma transcortin binding sites.
A Simple Dichromatic Densitometer for Repeated Measurements of Cardiac Output in Small Animals
Authors: Baines A. D. , Timanoff M. , Wong J. , Paul W.
Published: April 2011

The construction of a simple device for continuous monitoring and recording of plasma indocyanine green concentration in small animals is described. The apparatus is designed to hold a vascular bed such as the ear or the omentum and to transilluminate it with white light from a fiber optic bundle. The transmitted light is divided by a dichroic mirror. Appropriate filters select a narrow band of frequencies from each segment. There are two photovoltaic cells, one sensitive to the dye and the other insensitive to it. Both are approximately equally reactive to changes in transilluminence caused by changes in blood content or hematocrit and are relatively insensitive to changes in oxygen saturation of the transilluminated blood. Reproducible estimates of cardiac output have been obtained with the injection of 300 μg indocyanine green in a volume of 20 μl with the densitometer applied to the small intestine or to the ear of the animal. The device responds linearly to increasing plasma indocyanine green concentrations and can be calibrated with less than 0.1 ml of blood.
Reversal of Insulin Resistance by ATP in Hemorrhagic Shock
Authors: Chaudry Irshad H. , Sayeed Mohammed M. , Baue Arthur E.
Published: April 2011

Hemorrhagic shock was produced by bleeding rats to a mean arterial pressure of 40 mm Hg (1 mm Hg = 133 N/m2), which was maintained for 2 h. Muscles from these animals ('shock' muscles) showed resistance to the stimulation of glucose uptake by insulin. Addition of 1 mM ATP–MgCl2 to the medium had no effect on basal glucose uptake in either group of muscles, but it permitted insulin to exert its stimulatory effect in 'shock' muscles. An optimal insulin effect on glucose uptake in 'shock' muscles incubated without ATP was observed at an insulin concentration of 0.2 Unit/ml. When 1 mM ATP–MgCl2 was added to the medium, optimal insulin effect in 'shock' muscles was observed at an insulin concentration of 0.007 Unit/ml. Increasing the concentration of ATP–MgCl2 to 2.5 mM in the medium resulted in an optimal insulin effect at an insulin concentration of 0.001 Unit/ml in 'shock' muscles. Following 1 h incubation in Krebs–HCO3 medium, intracellular ATP contents of 'shock' muscles were approximately 50% lower than in control muscles. Addition of 1 mM ATP–MgCl2 to the incubation medium had no effect on the intracellular ATP contents of either group of muscles following incubation; however, 2.5 mM ATP–MgCl2 elevated intracellular ATP contents of 'shock' muscles but had no effect in control muscles. Possible mechanisms for this reversal of insulin resistance by ATP-MgCl2 in shock are discussed.
The Influence of [3H]Taurocholate on the Biliary Excretion of [14C]Acetylprocaine Amide Ethobromide
Authors: Kuo S. H. , Johnson G. E.
Published: April 2011

The biliary excretion rates of [14C]acetylprocaine amide ethobromide (acetyl-PAEB) and [3H]taurocholate, either administered alone or in combination to adult male Wistar rats, were studied. Their renal pedicles were ligated, and the common bile duct and one jugular vein cannulated. Acetyl-PAEB, 20 mg/kg, and sodium taurocholate, 70 mg/kg, were infused over a 5-min period. Blood and bile samples were collected every 10 min for 60 min. Liver samples were taken at 10 and 20 min. Approximately 100% of the administered taurocholate was excreted within 50 min. The simultaneous administration of acetyl-PAEB did not significantly alter the taurocholate excretion. The amount of the acetyl-PAEB dose excreted in 1 h was 9.4%. This was increased significantly to 16.5% when taurocholate was given concomitantly. The concentration of acetyl-PAEB in the bile increased significantly when taurocholate was given, and the ratios of its concentrations in bile–liver and bile–plasma were also increased. Taurocholate did not alter the liver–plasma concentration ratio of acetyl-PAEB. It is suggested that the concomitant administration of taurocholate increased the biliary excretion of acetyl-PAEB by facilitating its secretion by the liver into the bile.
Computation of Aortic Pulse Wave Velocity and Aortic Extensibility from Pressure Gradient Measurements
Authors: Lapointe Alain C. , Roberge Fernand A. , Nadeau Réginald A. , Thiry Pierre S. , Tremblay Gérard M.
Published: April 2011

This study is concerned with the computation of aortic pulse wave velocity based on simultaneous recordings of the aortic pressure gradient and first-time derivative of aortic pressure. These variables were recorded by means of a double-lumen catheter introduced in the aorta of four anesthetized closed chest dogs, and connected to critically damped manometer systems. Results of aortic pulse wave velocity were then compared: (i) to the true phase velocity obtained from spectra of apparent phase velocity, and (ii) to the pulse wave velocity computed from the time shift between maximum slopes of the pressure wave. From the aortic valves to 37 cm down the aortic trunk, pulse wave velocity increased from 410–460 cm/s to approximately 600–800 cm/s. Based on the wave propagation equation presented of Bramwell and Hill (Bramwell, J. C, and Hill, A. V. 1922. Proc. R. Soc. 93, 298–306), volumetric extensibility coefficients were computed from pulse wave velocity data. Results indicated that, from the aortic valves to 37 cm down the aorta, the mean volumetric extensibility decreased from 0.43–0.56% ΔV/cm H2O to 0.16–0.25% ΔV/cm H2O (1 cm H2O = 94.1 N/m2).
Re-incorporation of Carbon Atoms into Plasma Glucose in Newborn Dogs
Authors: Hall Susan E. H. , Hetenyi Jr. G.
Published: April 2011

The ratio of the total turnover rate of glucose calculated with [2-3 H]glucose as the tracer and the irreversible disposal rate of glucose, calculated with [U-14C]glucose as the tracer was found to be 1.35 ± 0.28 SD (± 0.08 SEM) in dogs 1–33 days of age. This value was unrelated to age and to the level of glucose in the plasma. Accordingly, under basal conditions the overall re-incorporation of carbon atoms into newly released glucose in pups is nearly identical with that found in grown dogs.
Poststenotic Dilatation: Arterial Wall Mechanics in Response to Vibration
Authors: Vito Raymond , Tso W. K. , Schwartz Colin J.
Published: April 2011

A study of the relationship between the mechanical response of human iliac arteries subjected to sinusoidally varying dynamic pressures superimposed on a static pressure of 100 mm Hg(1 mm Hg = 133 N/m2) and the development of arterial dilatation, with particular reference to poststenotic dilatation, has been conducted. In 13 experiments, optical measurements of the amplitude of vessel wall movements in response to dynamic pressures of amplitude 5 mm Hg peak to peak indicated the presence of at least one, and at most four resonance peaks for frequencies in the range 0–100 Hz. Four specimens were vibrated at resonance and four at frequencies 15 Hz higher than resonance, in response to a dynamic pressure of 5 mm Hg peak to peak for 3 h. All specimens exhibited some dilatation, the average percentage increase in diameter being in the range 0.22 to 0.42% per hour. In four additional experiments, the dynamic pressure was doubled at constant frequency. This resulted in an increased amplitude of vibration and additional dilatation at an increased rate. It is concluded that the dynamic stresses present in the vessel influence the rate of dilatation.
Subcellular and Functional Effects of Quinidine, Procaine Amide, and Lidocaine on Rat Myocardium
Authors: Harrow James A. C. , Dhalla Naranjan S.
Published: April 2011

Different antiarrhythmic agents such as quinidine, procaine amide, and lodocaine at 1 mM concentrations were found to depress the ability of an isolated perfused rat heart to generate contractile force. Quinidine, but not procaine amide or lidocaine, decreased calcium uptake by both mitochondrial and microsomal fractions at different concentrations of calcium. The mitochondrial phosphorylation rate, respiratory control index, and state 3 oxygen consumption, but not ADP:O ratio and state 4 oxygen consumption, were depressed by only quinidine. None of these agents had any effect on myofibrillar Mg2+-ATPase or Ca2+-stimulated ATPase activities. On the other hand, sarcolemmal Mg2+-ATPase and Ca2+-ATPase activities, but not Na+–K+-ATPase activity, were increased by all these drugs. The sarcolemmal adenylate cyclase (EC 4.6.1.1) activity was decreased by quinidine only. These results suggest some similarities and differences in the sites of action of quinidine, procaine amide, and lidocaine within the myocardium.
On the Specificity of Histamine H2-Receptor Antagonists in the Rat Cerebral Cortex
Authors: Phillis J. W. , Kostopoulos G. K. , Odutola A.
Published: April 2011

The effects of iontophoretically applied histamine H2-receptor antagonists and their antagonism of various amines, acetylcholine (ACh), and adenosine 5′-monophosphate (5′-AMP) were studied on spontaneously active rat cerebral cortical neurons. Metiamide selectively blocked the depressant actions of histamine. Burimamide, in amounts necessary for histamine antagonism, also antagonized the depressant effects of noradrenaline, dopamine, and 5-hydroxytryptamine. Neither antagonist affected 5′-AMP-induced depressions, but both reduced or blocked the excitatory actions of ACh. It is concluded that metiamide may be useful as a reliable antagonist of H2 receptors on cerebral cortical neurons.
Enhanced in vitro hepatic glucuronidation of thyroxine in rats following cutaneous application or ingestion of polychlorinated biphenyls
Authors: Bastomsky C. H. , Murthy P. V. N.
Published: April 2011

In rats four daily skin applications of a 30% solution of a polychlorinated biphenyl (PCB) mixture in mineral oil or of a microscope immersion oil, containing 34% PCB, led to increases in liver weight, protein concentration of the 10 000 × g supernatant fluid of liver homogenates and the in vitro glucuronidation of thyroxine (T4) by the supernatant fluid, whether related to liver weight or to protein concentration in the reaction mixture. Similar effects occurred after feeding 250 ppm (mg/kg) of PCB in either Purina chow or a low-iodine diet for 11 days. It is concluded that increased hepatic T4 glucuronidation contributes to the enhanced biliary excretion of T4 previously observed in PCB-treated rats.
Norepinephrine thermogenesis in seasonally acclimatized and cold acclimated red-backed voles in Alaska
Authors: Feist Dale D. , Rosenmann Mario
Published: April 2011

The calorigenic response (millilitres O2 per gram per hour) to injected norepinephrine (NE) was compared as an index of nonshivering thermogenesis (NST) in the following groups of the Alaskan red-backed vole (Clethrionomys rutilus): (1) summer, (2) fall acclimatized, (3) winter acclimatized, (4) 20 °C acclimated and (5) 5 °C acclimated. The metabolic response was tested at thermoneutrality (25 °C) and during cold exposure (5 °C).Winter acclimatized voles showed a significantly greater metabolic response to NE than summer voles at both 25 °C and 5 °C. In summer or winter voles the total metabolic rate after NE (MNE) was similar at 25 °C and 5 °C but the fraction of the total caused by exogenous NE was lower at 5 °C. Thus, thermogenesis during cold exposure and resulting from exogenous NE appear to be based on the same mechanism, and NE has thermoregulatory significance in these voles. The magnitude of the NE response in winter voles was comparable to the highest values reported for bats and exceeded levels reported for other adult small mammal species. Summer acclimatized voles and those acclimated to 20 °C in the laboratory were comparable in their response to NE but winter acclimatized voles were significantly more sensitive to NE than voles acclimated to 5 °C. The seasonal winter peak in MNE coincided with peaks previously found for maximum metabolic capacity (Mmax), maximum brown fat, and the period of coldest temperatures in December–January. The ratio of MNE to Mmax was similar throughout the year. The results suggest that small arctic–subarctic rodents have a greater capacity for NE stimulated NST than rodents from temperate latitudes probably because they are acclimatized to colder seasonal conditions.
Loss of ACTH biological activity in plasma during extraction with a commercial radioimmunoassay kit
Authors: Cowan John S.
Published: April 2011

The process used for extracting adrenocorticotropic hormone (ACTH) from plasma in the Searle ACTH immunoassay kit involves a loss of 70–100% of the biological activity of the ACTH.
The Influence of β-adrenergic antagonists on the adrenergic responses of the rat vas deferens
Authors: Tomei L. D. , Swamy V. C.
Published: April 2011

The influence of β-adrenergic antagonists (propranolol, pronethalol, alprenolol, iso-propylmethoxamine, H 35/25, sotalol and practolol) on isotonic contractile responses to norepinephrine (NE) was studied. All drugs caused an increase in the maximum responses while depressant effects were seen only with high doses of propranolol, pronethalol and alprenolol. The enhancement of responses to NE was considerably greater at low concentrations of calcium (0.5–1.0 mM) than at high (8 mM) concentrations. The inhibitory effects of propranolol, pronethalol and alprenolol were diminished but not completely overcome by increasing calcium concentrations from 1.8 to 8 mM. Cumulative dose-response curves of calcium showed no increase in maximum responses although responses to low concentrations of calcium were augmented by sotalol and practolol. Evidence suggests that the enhancing effects of these drugs may be due to their facilitatory effect on calcium mobilization following α-adrenoceptor activation while their depressant properties probably reflect their membrane stabilizing properties.
Anti-inflammatory and analgesic properties of etodolic acid in rats
Authors: Martel R. R. , Klicius J.
Published: April 2011

Etodolic acid (1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid) showed potent anti-inflammatory and analgesic properties in rats. In adjuvant arthritic rats etodolic acid was approximately six times more potent than phenylbutazone. In the carrageenin and the analgesic assays (inflamed paw pressure test) its potency was comparable to that of phenylbutazone. The potency of etodolic acid in the adjuvant arthritic rat suggests that this novel anti-inflammatory compound will be effective in the treatment of arthritic conditions of man.