bluuebunny/crossref_metadata_2025 huggingface dataset:
Biotransformation of glyceryl trinitrate to glyceryl dinitrate by human hemoglobin
Authors: Bennett Brian M. , Nakatsu Kanji , Brien James F. , Marks Gerald S.
Published: April 2011

The elimination of glyceryl trinitrate (GTN) by man is rapid and its clearance exceeds cardiac output. It is therefore clear that a variety of tissues in addition to liver are involved in the biotransformation of GTN. Incubation of GTN with the 25 000 × g supernatant fraction of lysed human erythrocytes resulted in a 39.6% ± 5.5 (SD) elimination of GTN after 40 min. After pretreatment of the lysate supernatant fraction with carbon monoxide, GTN elimination was only 26% ± 4.5. These data indicated that hemoglobin might be involved in GTN elimination. When purified hemoglobin was incubated with GTN, a 77.1% ± 6.4 elimination of GTN was observed, accompanied by glyceryl dinitrate formation. The biotransformation of GTN was inhibited by pretreatment with carbon monoxide. The results indicate that the biotransformation of GTN by human erythrocytes is due, at least in part, to interaction with hemoglobin.
Direct and indirect actions of histamine on airway smooth muscle in guinea pigs
Authors: Biggs D. F.
Published: April 2011

Studies in guinea pigs showed that some forms of drug-induced bronchospasm are reflexogenic involving afferents in the glossopharyngeal nerve. At least two pathways appear to be involved. One pathway contains H1 receptors and is blocked by mepyramine and sodium cromoglycate (SCG), and its pharmacological characteristics are similar to those of active reflex vasodilation. The other appears to involve peripheral muscarinic receptors. The findings also indicate that SCG may act on efferent as well as afferent pathways.
Mast cell heterogeneity
Authors: Shanahan F. , Denburg J. A. , Bienenstock J. , Befus A. D.
Published: April 2011

Increasing evidence for the existence of inter- and intra-species mast cell heterogeneity has expanded the potential biological role of this cell. Early studies suggesting that mast cells at mucosal sites differ morphologically and histochemically from connective tissue mast cells have been confirmed using isolated intestinal mucosal mast cells in the rat and more recently in man. These studies also established that mucosal mast cells are functionally distinct from connective tissue mast cells. Thus, mucosal and connective tissue mast cells differ in their responsiveness to a variety of mast cell secretagogues and antiallergic agents. Speculation about the therapeutic use of antiallergic drugs in disorders involving intestinal mast cells cannot, therefore, be based on extrapolation from studies of their effects on mast cells from other sites. Regulatory mechanisms for mast cell secretion may also be heterogeneous since mucosal mast cells differ from connective tissue mast cells in their response to a variety of physiologically occurring regulatory peptides. The development of techniques to purify isolated mast cell sub-populations will facilitate future analysis of the biochemical basis of the functional heterogeneity of mast cells.
5-Hydroxytryptamine synthesis, storage, and secretion from rat pancreatic acinar cells
Authors: Falardeau Pierre , Heisler Seymour
Published: April 2011

Pancreatic acinar cells are known to synthesize serotonin and dopamine from extracellular precursors. In this study, we found that small amounts of serotonin, alone, were preferentially stored in zymogen granules of acinar cells. Serotonin was apparently incorporated into mature rather than newly formed granules. This was based on the fact that the amine, rather than the newly synthesized zymogen protein, appeared first in the purified granule fraction; additionally, concentrations of cycloheximide, which markedly inhibited de novo synthesis of zymogen protein, did not affect the incorporation of serotonin into the granule fraction. Serotonin, synthesized by the acinar cells, can be secreted along with amylase in a time- and concentration-dependent manner following stimulation of acinar cells by a variety of pancreatic secretagogues. Whether serotonin secreted into pancreatic juice has a biological function remains unknown.
Resonance properties of the human elbow
Authors: MacKay William A.
Published: April 2011

In normal human subjects, elbow resonance was measured by driving the forearm over a range of frequencies. The relaxed forearm, in a manipulandum with a low inertial moment, had a resonance of 0.68 ± 0.06 Hz which was remarkably consistent for either sex and over a wide variety of arm sizes. Elbow stiffness, therefore, appears to be well adapted to the forearm moment of inertia. The resonant frequency increased as the elbow muscles were cocontracted, but the amplitude of resonance dropped exponentially because of increased damping. By 25% of maximum electromyogram levels the elbow was critically damped. Comfortable voluntary motion exhibited an amplitude–period relation very similar to that of forearm resonance, suggesting that significant use was made of resonance properties. It was found that the forearm was voluntarily oscillated at its resonant frequency within a specific range, characteristic for the individual. Depending on movement frequency, resonance can provide anything from a major to a negligible contribution to voluntary oscillatory motion. It would greatly increase efficiency of performance when antagonist muscles are kept as relaxed as possible to minimize damping.
Androgen inhibition of FSH-stimulated progesterone production by granulosa cells of prepubertal pigs
Authors: Evans Gareth , Lischinsky Adriana , Daniel Susan A. J. , Armstrong David T.
Published: April 2011

Androgens have been reported to stimulate progesterone production by granulosa cells of several species, and to act synergistically with FSH in stimulation of progesterone accumulation by rat granulosa cells. Studies were undertaken to examine the effect of androgens on FSH-stimulated progesterone production in culture by granulosa cells derived from prepubertal pig ovaries. When included in 24-h culture with FSH, both androstenedione and testosterone caused a reduction in progesterone accumulation, but dihydrotestosterone and androsterone did not. Granulosa cells were cultured for 24 h with FSH and [14C]progesterone with or without testosterone; testosterone did not affect the rate of overall metabolism of [14C]progesterone and it was therefore concluded that testosterone inhibited progesterone synthesis, rather than enhancing its catabolism. 17β-Estradiol also inhibited FSH-stimulated progesterone accumulation. To determine whether the action of testosterone was mediated by conversion to estradiol, granulosa cells were cultured with FSH and testosterone with or without an aromatase inhibitor (4-acetoxy-androstenedione). The aromatase inhibitor failed to prevent the testosterone-induced reduction in progesterone accumulation, although it markedly inhibited estradiol accumulation. These results indicate that theca-derived androgens can inhibit FSH-stimulated progesterone production by granulosa cells in the prepubertal pig, independently of estradiol.
Multiple responses to electrical field stimulation in circular muscle of canine gastric corpus
Authors: Sakai Yasushi , Daniel Edwin E.
Published: April 2011

Innervation of circular muscle of the canine stomach studied in vitro was investigated by subjecting muscle strips to electrical field stimulation. Strips were cut from the lesser curvature of the gastric corpus and stimulated with 10-s trains of 0.5-ms pulses at 0.5–20 Hz, 40 V. Most responses were classified into one of three types. In general, field stimulation tended to elicit sequences of varying magnitudes of transient on-contraction, on-relaxation, off-relaxation, off-contraction. Responses were abolished by tetrodotoxin. On-contraction was almost abolished by atropine plus desensitization by 5-hydroxytryptamine (5-HT) or substance P. On-relaxation and off-relaxation were not affected by adrenergic blockade, methysergide, apamin, or 4-aminopyridine. ATP usually caused contraction and slightly diminished relaxation to field stimulation. Vasoactive intestinal polypeptide (VIP) had little effect on tone and response to field stimulation. Relaxation disappeared after scorpion venom treatment. This probably resulted from depletion of the transmitter which mediates relaxation. Off-contraction was reduced by atropine, desensitization by 5-HT or substance P, cromoglycate, indomethacin or ATP, but was not affected by adrenergic blockade, hexamethonium, methysergide, mepyramine, or VIP. The findings suggest that innervation of gastric corpus circular muscle included excitatory cholinergic and both excitatory and inhibitory noncholinergic, nonadrenergic innervation. However, the responses of circular muscle to field stimulation in vitro were drastically different from those obtained previously in vivo, suggesting damage or altered inputs to circular muscle when strips of circular muscle are studied.
Glutamine enhances glutamate release in preference to γ-aminobutyrate release in hippocampal slices
Authors: Szerb John C. , O'Regan Patrick A.
Published: April 2011

To see the effect of physiological concentrations of glutamine on glutamate and γ-aminobutyrate (GABA) release, rat hippocampal slices were incubated and (or) superfused without or with 0.25 mM glutamine in the presence or absence of Ca2+. The spontaneous and high K+-evoked release of glutamine, glutamate, and GABA was measured by precolumn derivatization and reversed phase high performance liquid chromatography. The spontaneous release of glutamate was increased by super-fusion with glutamine and this increase was three times greater in the absence than in the presence of Ca2+. Spontaneous GABA release was not increased by glutamine. While in the absence of glutamine, the release of glutamate and GABA evoked by 50 mM K+ was about equal, in the presence of glutamine the evoked release of glutamate was nearly three times greater than that of GABA. The large evoked release of glutamate in the presence of glutamine was Ca2+ dependent nearly to the same extent as the smaller evoked release in the absence of glutamine. Results suggest that the availability of extracellular glutamine regulates the release of glutamate but not of GABA. Extracellular Ca2+ controls the spontaneous conversion of glutamine to glutamate but the site and mechanism of this control is uncertain.
Insulin response in rats acutely exposed to cold
Authors: Smith Ora L. K.
Published: April 2011

To examine the role of insulin during shivering thermogenesis, rats (unacclimatized) were exposed to 4 °C for 24 h and compared with control rats kept at 25 °C. Cold exposure lowered plasma insulin levels by one half, despite unchanged plasma glucose concentrations. Adrenodemedullation 2 weeks prior to cold exposure partially restored the ability of cold rats' plasma insulin levels to respond to a glucose load, unless it was accompanied by a subcutaneous injection of epinephrine. When additional normal rats were cold stressed and injected immediately after exposure with an α-adrenergic blocking agent (phentolamine), an intravenous glucose challenge caused a mean peak insulin value that was 50% higher than that of untreated controls, while the glucose level was less elevated. The results suggest that cold depresses blood insulin levels through activation of the sympathetic adrenal system, an effect most likely mediated by α-adrenergic inhibition of the pancreatic insulin response.
Effect of acid–base status on plasma phosphorus response to lactate
Authors: Oster James R. , Alpert Helen C. , Vaamonde Carlos A.
Published: April 2011

The mechanism(s) underlying the hyperphosphatemia of lactic acidosis is uncertain. We assessed the interacting influence of the acid anion and acid–base status on plasma phosphorus concentration by administering lactic acid alone, lactic acid plus sodium bicarbonate, sodium bicarbonate alone, and sodium lactate alone to four different groups of dogs. The findings of (1) no increase in plasma phosphorus concentration with lactic acid plus sodium bicarbonate versus a marked increment with lactic acid alone, and (2) no difference in the plama phosphorus response to sodium lactate versus sodium bicarbonate indicate that acidemia is necessary for the expression of lactate-induced hyperphosphatemia. The apparent greater propensity for marked hyperphosphatemia in lactic acidosis than in other types of metabolic acidosis remains unexplained, but conceivably might relate to differences in intracellular pH and in the rate of glycolysis.
Disappearance kinetics of 2,4- and 3,4-dichlorophenol in a fluvial system
Authors: Carey J. H. , Fox M. E. , Brownlee B. G. , Metcalfe J. L. , Platford R. F.
Published: April 2011

The disappearance rates of 2,4- and 3,4-dichlorophenol in a small stream were studied and were shown to be first order with respect to either distance or time of flow. Both chlorophenols disappeared at approximately the same rate with average half-lives in the stream of about 4 h. The absence of seasonal variability in the rate constants along with the observance of first order kinetics over several ecological zones of the stream led to the conclusion that the rate controlling factor was not biological. It is suggested that the disappearance was due to degradation within the biofilm covering the stream bed and that the rate is controlled by diffusion of the chlorophenols across the water–biofilm interface.
Kainic acid evoked release of D-[3H]aspartate from rat striatum in vitro: characterization and pharmacological modulation
Authors: Notman H. , Whitney R. , Jhamandas K.
Published: April 2011

A presynaptic stimulatory action of kainic acid (KA) on the release of glutamate from corticostriatal neurons is thought to contribute to the toxic effect of KA on cell bodies of neurons in the striatum. To characterize the action of KA on the presynaptic amino acid release, its effect was evaluated on the spontaneous efflux of D-[3H]aspartate (D-[3H]Asp), a marker for glutamatergic neurons, from slices of rat striatum in superfusion experiments. In the concentration range 0.5–10.0 mM, KA significantly increased the spontaneous efflux of D-[3H]Asp. Under similar conditions potassium (K+, 25 mM), veratridine, D-aspartic acid (D-Asp), and N-methyl-D-L-aspartic acid (NMDLA) also induced the efflux of the radiolabelled amino acid. The stimulatory effect of KA, like that of K+, was partly calcium dependent. The action of veratridine, D-Asp, and NMDA was not calcium dependent. Tetrodotoxin (TTX) blocked the action of veratridine on D-[3H]Asp efflux but did not affect the action of KA. In a sodium-free perfusion medium the action of KA was greatly reduced. Dihydrokainic acid produced an effect on D-[3H]Asp efflux comparable in magnitude with that produced by KA. The latter, at a dose of 5 mM, also stimulated the efflux of D-[3H]Asp from the cortex, hippocampus and the septum but its effect on these regions was weaker than its striatal effect. The action of several agents, which previously have been found to depress transmitter release in other systems and (or) to modify the neurotoxic action of KA in vivo, was evaluated on the KA-evoked D-[3H]Asp efflux from striatal slices. Both dopamine and a dopamine receptor agonist, bromocryptine, significantly attenuated this KA-evoked efflux. Other agents (adenosine, atropine, baclofen, carbachol, D-Ala2-D-Leu5-enkephalin, ethanol, flurazepam, γ-aminobutyric acid, glutamate diethyl ester, morphine, and proline) did not modify the stimulatory action of KA on the efflux of D-[3H]Asp. A comparison between the effects of these pharmacological agents on amino acid efflux and their previously reported actions on KA-induced neurotoxicity revealed no obvious association. This observation, as well as a discrepancy between the concentrations of KA affecting transmitter release and exerting a neurotoxic action, suggests that the presynaptic action of KA may not play an important role in its damaging action on striatal neurons.
Indocyanine green pharmacokinetics in the rabbit
Authors: Thiessen J. J. , Rappaport P. L. , Eppel J. G.
Published: April 2011

In a Latin square design, nine New Zealand white male rabbits (2.8 – 4.8 kg) each received intravenous indocyanine green (ICG) in doses of 2.5, 12.5, and 25 mg/kg. A period of 4 weeks separated consecutive experiments. A specific high-pressure liquid chromatographic (HPLC) assay and the traditional spectrophotometric (SPEC) method were used to monitor plasma ICG. The analyses demonstrated the ambiguous nature of the SPEC assay, and the HPLC procedure pointed to the presence of an unidentified ICG metabolite. Dose-dependent ICG disposition was evident from the ANOVA of the mean (±SD) clearances, namely, 17.09 (7.35), 4.50 (0.82), and 2.27 (0.57) mL∙min−1∙kg−1 for the aforementioned doses, respectively. Analysis of variance of the clearances also demonstrated a significant ordering effect suggesting cumulative ICG toxicity. The mean ICG profiles for the three doses accorded with a novel three-compartment model containing two ICG distributional spaces in addition to a compartment (liver) responsible for ICG elimination from the circulation. A saturable uptake process into the eliminating compartment (Vmax = 0.93 mg∙kg−1∙min−1; Km = 31.9 mg/L) accounted for the dose-dependent features. Additional studies in four unanesthetized rabbits with chronically catheterized bile ducts revealed no disparity between the SPEC and HPLC analyses of biliary ICG. The mean (±SD) ICG recovery in bile following an intravenous dose of about 12.5 mg/kg was 59.8 (16.3)%.
Motilin and the vagus in dogs
Authors: Lemoyne M. , Wassef R. , Tassé D. , Trudel L. , Poitras P.
Published: April 2011

The aim of this work was to determine the influence of the vagus on the circulating levels of immunoreactive (IR) motilin. Five mongrel dogs were equipped with chronically implanted electrodes in the small intestine to record the myoelectrical activity. The release of IR motilin during fasting, after a meal, and during an infusion of insulin was studied before and after truncal vagotomy at the diaphragmatic level. When tested at least two weeks after the operation, the motility pattern of the small intestine and the secretion of IR motilin remained unaltered by vagal section. Cyclic increases in IR motilin associated with phase III's of the interdigestive myoelectric complexes were still observed after vagotomy (maximum levels of IR motilin: 250 ± 37 versus 239 ± 19 fmol∙mL−1, not significant), and they were still abolished by feeding or by insulin. However, an inhibitory influence can probably be mediated by the vagus since, in normal animals, vagal stimulation by a "modified sham feeding" (tease feeding or presentation of food) at the beginning of a period of phase III activity promptly interrupted this part of the complex and decreased significantly the release of IR motilin by about 20%. The release of motilin is not chronically altered by distal vagotomy in dogs.
Age and day–night changes in clonidine-induced analgesia in mice
Authors: Hirst M. , Kavaliers M. , Teskey G. C.
Published: April 2011

Administrations of clonidine hydrochloride (0.1, 1.0 mg/kg) to young, mature, and old mice influenced their response time on a thermally aversive surface (50 °C) in an age-dependent manner. This analgesic effect was of short duration. During daytime measurement periods, young and mature mice showed significantly greater analgesic responses than did the old animals. Although all animals were able to perform the appropriate paw-licking response, the old mice displayed tremors and locomotor disturbances after receiving clonidine. These effects were not seen in the younger groups. Both the young and mature animals showed a substantial enhancement of their analgesic responses after receiving clonidine at night, whereas a significant but much reduced nighttime increase in antinociceptive effect was seen in old animals. Yohimbine, but not prazosin, inhibited clonidine-induced analgesia in young animals. Old mice given combinations of clonidine and these adrenergic antagonists showed elevations in response times, accompanied by severe behavioural changes.
Protein synthesis in compensatory hypertrophy of rat plantaris
Authors: Noble Earl G. , Tang Qian , Taylor Paul B.
Published: April 2011

Protein synthesis in rat plantaris muscle undergoing surgically induced hypertrophy was studied using a perfused hindquarter preparation. The tissue mass of the hypertrophied muscle increased 11, 33, 33, and 104% at 2, 5, 15, and 50 days postsurgery. Total tissue protein synthesis was unchanged during the early phase but was significantly elevated after 15 and 50 days of work overload. Myosin synthesis was also significantly elevated after 15 and 50 days of hypertrophic growth. Increases in muscle protein content (milligrams per muscle) for each protein fraction examined were temporally in step with the altered synthetic rates. The shift in muscle fibre-type profile from approximately 10% alkaline-labile fibres in the control muscle to about 25% alkaline-labile fibres in the hypertrophied muscle also followed a similar time course. These data suggest that during compensatory hypertrophy, enhanced protein synthesis may be the dominant mechanism for the massive accumulation of muscle protein. However, its contribution to muscle growth does not become evident until about 15 days after the initial growth stimulus.
Binding and degradation studies on angiotensin II
Authors: Grover A. K. , Kwan C. Y. , Kostka P. , Shephard S. M. , Daniel E. E.
Published: April 2011

125I-labelled angiotensin II (AII) and [3H]AII showed specific binding to rat mesenteric artery microsomes. The binding in either instance was inhibited by the AII analog saralasin. [3H]AII was not degraded by the microsomes but 125I-labelled AII was degraded. Autoradiography of thin layer chromatograms of 125I-labelled AII treated with microsomes showed the parent peak (Rf = 0.4–0.45) and a single major degradation product peak (Rf = 0.25–0.30), and [125I]NaI had an Rf value higher than both 125I-labelled AII and its degradation product. Chromatography of unlabelled AII or [3H]AII gave the same Rf value as 125I-labelled AII, but unlabelled AIII moved with Rf = 0.55–0.60. The formation of the degradation product was time and membrane concentration dependent. The degradation occurred at pH 6 and 7 but not at pH 8. However, specific binding of 125I-label1ed AII was also lower at pH 8. The degradation could not be completely inhibited by the use of crude particulate fractions instead of microsomes, by preparing membranes in presence of protease inhibitors, or by including protease inhibitors and sulfhydryl agents in the assay medium. However, the degradation product neither showed specific binding to the microsomes nor interfered with the specific binding of 125I-labelled AII. Furthermore, the tightly bound material eluted from the microsomes in presence of 0.05 M acetic acid at 0 °C consisted predominantly of the parent compound. The implications of these findings are discussed both in terms of validity of the binding experiments and possible relationship between the degradation and the receptor binding sites in the membrane.
Dibutyryl cyclic AMP increases phosphodiesterase activity in the rat heart
Authors: Palmer Warren K. , Doukas Sylvia
Published: April 2011

The influence of increasing the in vivo concentration of cyclic AMP on the activity of cyclic nucleotide phosphodiesterase (PDE) in rat heart was investigated. One, three, and five hourly injections of 5.0 mg dibutyryl (Bt2) cyclic AMP significantly increased the activity of PDE in the supernatant fraction of rat heart using 1.0 μM cyclic AMP as the assay substrate concentration. When 100 μM cyclic AMP was used in the assay reaction, increases in enzymes activity were seen following five and eight nucleotide injections. The nucleotide-induced increase in PDE activity was dose dependent. When the five-injection protocol was used, PDE activity remained elevated for at least 4 h, while activity had returned to control levels within this time when two hourly injections were used. The nucleotide stimulation of PDE activity was blocked by cycloheximide. Five hourly infections of Bt2 cyclic AMP increased PDE activity in the liver and fast-twitch red muscle. A reduction in PDE activity in fast-twitch white muscle was seen following nucleotide injections. These findings are consistent with the hypothesis that prolonged elevations in the intracellular concentration of cyclic AMP cause an elevation in myocardial PDE activity. The increased activity seems to be the result of protein synthesis. These data suggest that cyclic AMP contributes significantly in regulating its own metabolism in the rat heart.
Specific high affinity binding of the calcium channel antagonist, [3H]nitrendipine, to rat liver microsomes
Authors: Gopalakrishnan V. , Triggle C. R.
Published: April 2011

Some key properties of the binding of [3H]nitrendipine, an analogue of the 1,4-dihydropyridine, nifedipine, to a plasma membrane enriched microsomal fraction from the rat liver are described. Specific binding was saturable, linear with protein concentration, and reversible. The apparent equilibrium dissociation constant, KD, was 4.20 ± 0.22 nM and the maximum density of binding, Bmax, was 3.02 ± 0.17 pmol/mg of protein determined from Scatchard analysis of binding at 10 °C. Inhibition of binding was specific for dihydropyridines with competitive inhibition being noted with nifedipine and 4-chloronifedipine, as well as BAY K-8644, a calcium channel agonist. A biphasic displacement curve was recorded for methoxy verapamil (D-600), and a triphasic competition curve with lanthanum (La3+), and diltiazem demonstrated competitive kinetics. The high affinity binding site for nitrendipine in the liver, although having some similar properties to those sites described in skeletal muscle, would appear to be distinctive with respect to its unique sensitivity to D-600 and diltiazem. We speculate that this binding site may represent a Ca2+ channel responsible for regulating Ca2+ influx and hepatic glycogenolysis.
Effect of temperature and Zn2+ on isometric contractile properties and electrical phenomena of frog (Rana) and Xenopus skeletal muscle fibers
Authors: Oba Toshiharu , Takagi Yumiko , Hotta Ken
Published: April 2011

Effects of temperature and Zn2+ on the isometric contractile properties of toe muscle fibers of Rana catesbeiana and Xenopus laevis were studied. The maximum twitch tension almost doubled when the temperature was lowered from 20 to 4 °C in Rana muscles but not in Xenopus muscles, although the duration of action potential in Xenopus muscle was increased slightly more than that seen in the Rana species. The maximum rate of rise of tension was greater in Xenopus muscle than in the Rana muscle, at 20 °C. The prolongation of the time-to-peak tension following exposure to low temperature (4 °C) was more pronounced in Rana than in Xenopus muscles. These results suggest that the speed of release and reuptake of Ca2+ by the sarcoplasmic reticulum (SR) differs in Rana and Xenopus muscles and that these factors may be related to differences in the SR and the T-tubular morphology. In Rana muscles, Zn2+ prolonged the falling phase of the action potential and potentiated the twitch tension. In Xenopus muscles, Zn2+ marginally prolonged the duration of action potential and the twitch tension was not markedly potentiated. These results indicate that Zn2+ potentiates the twitch tension by prolonging the action potential and that Rana muscles are more sensitive to the effects of Zn2+.
Contractile effects of 4-aminopyridine on isolated frog rectus abdominis muscles
Authors: Savage A. O.
Published: April 2011

The contractile effects of 4-aminopyridine (4-AP) on isolated frog rectus abdominis muscles were examined, and compared with KCl-induced contractures. 4-AP (1 – 40 mM) caused slowly developing, concentration-dependent contractures which were not modified by (+)-tubocurarine (2.7 – 13.3 μM). The contractures were prolonged and very slowly relaxed (>30 min) on washout. KCl-induced contractures developed more rapidly and relaxation was equally rapid, both occurring within 90 s of application and washout, respectively. KCl contractures were slightly but significantly (P < 0.05) attenuated by (+)-tubocurarine in concentrations that blocked carbachol contractures. In calcium-free Ringer's solution, KCl (10–120 mM) responses were completely abolished, but 4-AP concentration–response curves were shifted to the right three- to four-fold. The results show that 4-AP causes contracture of the frog rectus abdominis. It is suggested that at the lower concentration employed (<10 mM), 4-AP increases extracellular calcium entry into the muscle, while larger concentrations produce contractures by a direct intracellular mechanism. 4-AP contractures were independent of postjunctional nicotinic cholinoceptor activation.
Increased pituitary thyroxine 5′-deiodinase activity in adult rats rendered hyper- or hypo-thyroid during perinatal life
Authors: Walker Peter
Published: April 2011

Perinatal thyroid dysfunction in the rat leads to permanent alterations in pituitary TSH secretion in the adult animal. Thus, neonatal hyperthyroidism (NH) and perinatal hypothyroidism (PH) both result in apparent increased pituitary sensitivity to the feedback effects of thyroid hormones in the adult rat. To determine if increased intrapituitary generation of triiodothyronine (T3) might account for these observations, we measured thyroxine (T4) 5′-deiodinase activity in pituitary homogenates of adult NH and PH rats. NH was induced by injecting neonatal rats with 12 daily sc injections of T4 (0.4 μg/g body weight (BW)). Control rats received vehicle alone. PH was induced by administering 0.05% 6-n-propylthiouracil in the drinking water to pregnant dams from the 16th day of gestation through the 12th day postpartum. Thereafter, a normal water supply was substituted. NH and PH rats were allowed to mature and were sacrificed at 105 days of age. Serum T4, T3, and TSH concentrations were measured by radioimmunoassay. Pituitary T4 5′-deiodinase activity was assessed by the measurement of T3 formation by pituitary homogenates incubated in the presence of 0.65 μM T4 and 100 mM dithiothreitol at 37 °C for 90 min. Body weights of adult NH and PH rats were slightly but not significantly decreased compared with control rats. Relative pituitary gland weight (milligrams per 100 g BW) was significantly decreased in adult PH rats (P < 0.005) but not in adult NH rats. In adult NH rats, serum T4 and T3 concentrations were significantly decreased (P < 0.01) compared with control rats. Serum TSH concentrations were similar. No significant differences in serum T4, T3, and TSH concentrations were noted between adult PH and control rats. Pituitary T4 5′-deiodinase activity was significantly increased in both adult NH and PH rats compared with controls (NH > PH > control; P < 0.005, and P < 0.05, respectively). These data indicate that pituitary T4 5′-deiodinase activity is significantly increased in adult NH and PH rats. Increased pituitary T4 5′-monodeiodination may explain, in part, the apparent increased thyrotroph sensitivity to feedback effects of thyroid hormone in these animals.
Subcellular localization of oxytocin in the ovine corpus luteum
Authors: Rice G. E. , Thorburn G. D.
Published: April 2011

The subcellular localization of oxytocin within the corpus luteum of sheep was investigated using differential and density gradient centrifugation. Oxytocin was associated with a particulate fraction which sedimented to a density of 1.054 – 1.061 g/mL. The exclusion of [3H]oxytocin from this particulate fraction is indicative that particulate oxytocin represents endogenous compartmentalization. Particulate oxytocin, incubated in buffered medium at 37 °C, was stable for up to 1 h and the release of oxytocin was not affected by the pH of the incubation medium, over the range 5.5 – 8.5. Oxytocin release, however, was stimulated by incubating particle-bound oxytocin in buffered medium of low osmolality (<200 mosmol). These data are similar to the physicochemical properties reported for peptide-containing neurohypophysial secretory granules. Ultrastructural analysis of oxytocin-containing fractions revealed the presence of electron-dense granules (diameter, 200–250 nm). These data are suggestive that oxytocin, in the corpus luteum of sheep, is contained within a population of secretory granules which occur in high numbers during the midluteal phase of the oestrous cycle.
Valproic acid disposition in rabbits during chronic treatment with Escherichia coli endotoxin
Authors: Thiessen J. J. , Albright P. S. , Bruni J. , Suria D.
Published: April 2011

The disposition of valproic acid (VPA) in rabbits was studied after chronic treatment with Escherichia coli endotoxin. Endotoxin (1–2 μg/kg) was administered daily to 10 male New Zealand white rabbits for 5 days. On day 5, 50 mg/kg of VPA was given iv during the time of the peak febrile response. Blood samples were drawn at appropriate time intervals and analyzed for free and total VPA levels as well as plasma proteins and free fatty acids. The data were compared with similar control experiments performed 2 weeks before and after endotoxin treatment. Pharmacokinetic analysis indicated that the changes in free VPA clearance after endotoxin were related to the change in the febrile response during chronic treatment (r = 0.77; p < 0.05); that is, animals which developed tolerance to the febrile response showed elevated drug clearance, whereas nontolerant animals showed decreased clearance of VPA.
Ionic permeability and blood pressure
Authors: Sutter Morley C.
Published: April 2011

The difficulty of establishing a causal relationship between any measured phenomenon and hypertension is emphasized. The literature concerning ion movements in tissues from hypertensive patients and animals is briefly reviewed. It is pointed out that the evidence (i) is conflicting concerning changes of permeability of red blood cells in patients with hypertension; (ii) is more consistent in leukocytes; and (iii) is virtually nonexistent regarding ionic permeability of blood vessels from man. A few studies suggest that permeability to calcium is altered in aortae from hypertensive animals and that concentrations of calcium in platelets are correlated with blood pressure in man. Some of our previously published work on red blood cells is then summarized which suggests that altered passive permeability to calcium exists in red blood cells from spontaneously hypertensive rats. Experiments are described using the calcium antagonists D-600 or felodipine to further study previously reported differences in calcium handling in blood vessels from spontaneously hypertensive rats. We could detect no difference in the effects of these calcium antagonists on blood vessels from hypertensive animals compared with controls. It is suggested that the finding of increased passive permeability to calcium in tissues from hypertensive animals is a lead worth pursuing.
Development of enteropeptidase activity in mouse small intestine: influence of hormones
Authors: Arsenault Pierre , Ménard Daniel
Published: April 2011

The postnatal development of enteropeptidase activity has been examined on mucosal scrapping of the proximal part of the mouse small intestine. The activity was present at birth and remained low during the first 15 days of life. Then it rapidly increased reaching adult level within 2 days. Daily administration of cortisone acetate (25 μg∙g body weight (bw)−1∙day−1), insulin (12.5 mU∙g bw−1∙day−1), or epidermal growth factor (4 μg∙g bw−1∙day−1) during 3 days to 8-day-old mice induced a premature increase of enteropeptidase. The maximal increase was observed with cortisone treatment, the enzymic activity representing 70% of the adult level. Thyroxine alone (1 μg∙g bw−1∙day−1) had no significant effect on enteropeptidase activity. Hormonal interactions have been evaluated by studying the effects of different hormonal combinations. Finally, cortisone acetate which has a major effect on this activity during suckling period was unable to influence adult small intestinal enteropeptidase activity.
Chronic treatment of rats with D-600 causes a compensatory decrease in the calcium requirement for contractility of vascular smooth and cardiac muscles
Authors: Pang Catherine C. Y. , Sutter Morley C.
Published: April 2011

We studied the effects of chronic hypotensive treatment of normotensive Wistar rats (NWR) with methoxyverapamil (D-600) and hydralazine on in vitro contractile response of aortic strips, portal vein strips, and Langendorff-perfused hearts in normal (2.5 mM) and low (0.2 mM) calcium (Ca). Portal vein strips from rats treated with D-600, compared with the same strips from control and hydralazine-treated rats, developed greater spontaneous contractile activity in normal Ca and retained greater responses to norepinephrine (NE) and 80 mM K in low Ca. Aortic strips from all three groups of rats retained similar responses to NE and K in low Ca. Hearts from D-600-treated rats produced less intraventricular pressure (IVP) to isoproterenol (ISO) than hearts from control and hydralazine-treated rats in normal Ca but greater IVP to ISO than hearts from the other two groups of rats in low Ca. Thus, chronic treatment of NWR with D-600 but not with hydralazine resulted in the reduction of Ca requirement for contractile activities of the portal vein and the myocardium.
Symposium Nutrition and metabolic development
Authors: Hahn Peter
Published: April 2011

Perinatal changes in metabolic processes owing to a change from a high carbohydrate to a high fat (milk) diet at birth are described. It is pointed out that early changes in food composition may have permanent effects and it is suggested that, in the rat, this may be due to structural alterations in the brain at a time when it is still differentiating. Such changes are irreversible.
Gastrointestinal peptides and the adaptation to extrauterine nutrition
Authors: Lucas Alan , Bloom Stephen R. , Green Albert Aynsley
Published: April 2011

The adaptation to extrauterine nutrition involves complex physiological changes at birth which may be regulated by genetic endowment; enteral nutrients, secretions, and bacteria; and endogenous hormones and exogenous hormones in breast milk. The hypothesis is explored that enteral feeding after birth may trigger key adaptations in the gut and in metabolism partly through the mediation of gastrointestinal hormone secretion. Gut peptides are found in the early human fetal gut and by the second trimester some are found in high concentrations in the fetal circulation and amniotic fluid. Major plasma hormonal surges occur during the neonatal period in term and preterm infants: notably in enteroglucagon, gastrin, motilin, neurotensin, gastrointestinal peptide, and pancreatic polypeptide. These events do not occur in neonates deprived of enteral feeding. A progressive development of dynamic gut hormonal responses to feeding is observed. The pattern of gut endocrine changes after birth is influenced by the type and route of feeding. Potential pathophysiological effects of depriving high risk neonates of enteral feeding are considered. It is speculated that infants committed to prolonged total parenteral nutrition from birth may benefit from the biological effects of intraluminal nutrients used in subnutritional quantities.
Evidence for a contribution by brown adipose tissue to the development of fever in the young rabbit
Authors: Harris W. H. , Foster D. O. , Nadeau B. E.
Published: April 2011

This study was undertaken to determine if brown adipose tissue was involved in heat production during fever produced by S. abortus equi (1 μg) in unanesthetized rabbits aged 19–26 days. The fever (0.9–1.6 °C) occurred after a delay of 20–30 min and was frequently biphasic. Radiolabelled microspheres for measuring tissue blood flow were injected intraventricularly into three groups of animals: rabbits not given pyrogen, rabbits in which the febrile response to pyrogen was developing, and rabbits in which the febrile response had peaked. Blood flow to brown fat deposits and other organs was calculated from the fractional distribution of the microspheres and the recovery of microspheres in a reference arterial blood sample. At the fever peak, blood flow to brown fat was not significantly different (p > 0.05) from the control value (0.9 ± 0.2), but during the rising phase of the fever the flow increased significantly (p < 0.01) to 2.6 ± 0.4 mL min−1 g−1. The blood flow to muscles of the forelimbs and hind limbs was also increased significantly (p < 0.05) during the rising phase of the fever. No significant change in blood flow to other organs or tissues was found during the rising phase of the fever. These results indicate that both nonshivering as well as shivering thermogenesis contribute to heat production during development of fever in the young rabbit. However, nonshivering thermogenesis was not involved in the maintenance of the elevated body temperature after the fever had peaked.
The renal handling of human urinary ribonuclease by rat kidneys
Authors: Farboody G. , Tattrie B. , Rippstein P. U. , Rabin E. Z.
Published: April 2011

The purpose of the study was to find out how poly(C)-avid human urinary ribonuclease is handled by the kidney. Purified human urinary ribonuclease (molecular weight 33 000) was radiolabelled with 125I. The enzyme was injected intravenously into dogs and monkeys with and without kidneys. The disappearance rate from the animals without kidneys was markedly prolonged. In the dog and monkey with kidneys, the radiolabelled enzyme which was infused was recovered in the urine unchanged. No large molecular weight fragments were found. When 125I-labelled ribonuclease was infused into rats the material recovered in the urine was primarily identical with the material infused. A very small fraction of the material recovered was found to contain some fragments which had chromatographic characteristics of monoiodotyrosine and diiodotyrosine. Two other fragments were detected but could not be identified. Autoradiographic studies of the rat kidneys also showed some reabsorption of the radiolabelled ribonuclease, particularly in the proximal tubules. With electron microscopy the radiolabelled material could be seen in the lysosomes. These observations corroborate findings discovered for other low molecular enzyme such as lysozyme (molecular weight 14 000) and suggest that the human ribonuclease is mainly excreted by the kidneys unchanged and that a minor amount may be reabsorbed by the proximal tubules and metabolized in the lysosomes.
Role of alpha-adrenergic receptors in the intrinsic inotropic selectivity of dobutamine in anesthetized dogs
Authors: Shaffer Joel E. , Gorczynski Richard J.
Published: April 2011

The inotropic selectivity of dobutamine was examined in pentobarbital-anesthetized, vagotomized dogs pretreated with a ganglion blocker. The purpose was to determine if, in the presence of hexamethonium and vagotomy, the inotropic selectivity of dobutamine could be attributed to an action of dobutamine on alpha-adrenoreceptors. Dose–response curves were determined for either isoproterenol or dobutamine 30 min after treatment with hexamethonium (20 mg/kg). Analysis of heart rate versus right ventricular contractile force showed that dobutamine produced less tachycardia for a given increase in contractile force than isoproterenol; this was statistically significant when contractile force was increased by either 50 or 100%. In a separate series of experiments, dobutamine (8 μg∙kg−1∙min−1) was administered 20 min after propranolol (3 mg/kg). Under these conditions there was a slight increase in contractile force which represented 12% of the dobutamine response prior to propranolol administration. This increase in contractile force in the presence of propranolol was completely prevented by the addition of phentolamine (1 mg/kg). Consequently, in another series of experiments, dose–response curves for dobutamine were performed in the presence of hexamethonium before and 30 min after phentolamine alone (1 mg/kg) or vehicle. Phentolamine did not influence the effect of dobutamine on heart rate or contractile force, but prevented the increase in diastolic blood pressure caused by dobutamine. In addition, analysis of heart rate versus contractile force indicated that there were no statistically significant effects of phentolamine on the inotropic selectivity of dobutamine. Thus, it appears that dobutamine may exert an effect on myocardial contractility through activation of alpha-adrenoreceptors; however, this effect is so minimal that in the presence of hexamethonium and vagotomy, activation of alpha-adrenoreceptors does not appear to influence the inotropic selectivity of dobutamine.
Vagal afferent activity and renal nerve release of dopamine
Authors: Morgunov N. , Baines A. D.
Published: April 2011

To investigate the involvement of vagal afferents in renal nerve release of catecholamines, we compared norepinephrine, dopamine, and epinephrine excretion from innervated and chronically denervated kidneys in the same rat. The difference between innervated and denervated kidney excretion rates was taken as a measure of neurotransmitter release from renal nerves. During saline expansion, norepinephrine excretion from the innervated kidney was not statistically greater than from denervated kidneys. Vagotomy increased norepinephrine release from renal nerves. Thus vagal afferents participated in the suppression of renal sympathetic nerve activity during saline expansion. No significant vagal control of dopamine release by renal nerves was detected under these conditions. Bilateral carotid ligation stimulated renal nerve release of both norepinephrine and dopamine in saline-expanded rats. The effects of carotid ligation and vagotomy were not additive with respect to norepinephrine release by renal nerves. However, the baroreflex-stimulated renal nerve release of dopamine was abolished by vagotomy. Electrical stimulation of the left cervical vagus with a square wave electrical pulse (0.5 ms duration, 10 V, 2 Hz) increased dopamine excretion exclusively from the innervated kidney of hydropenic rats. No significant change in norepinephrine excretion was observed during vagal stimulation. Increased dopamine excretion during vagal stimulation was associated with a larger natriuretic response from the innervated kidney than from its denervated mate (p < 0.05). We conclude that under appropriate conditions vagal afferents stimulate renal release of dopamine and produce a neurogenically mediated natriuresis.
Force–velocity relationships in hypertensive arterial smooth muscle
Authors: Packer C. S. , Stephens N. L.
Published: April 2011

Increased total peripheral resistance is the cardinal haemodynamic disorder in essential hypertension. This could be secondary to alterations in the mechanical properties of vascular smooth muscle. Adequate study has not been made of the force–velocity (F–V) relationship in hypertensive arterial smooth muscle. Increased shortening in arterial smooth muscle would result in greater narrowing of arteries. The objectives of this investigation were to see if there is (i) increased shortening or increased maximum change in muscle length (ΔLmax where L stands for muscle length), (ii) an increased maximum velocity of shortening (Vmax) measured in lo per second where lo is the optimal muscle length for tension development, and (iii) a difference in maximum isometric tension (Po) developed in spontaneously hypertensive rat (SHR; N = 6) compared with normotensive Wistar Kyoto rat (WKY; N = 5) caudal artery strips. An electromagnetic muscle lever was employed in recording force–velocity data. Analysis of these data revealed the following: (a) the SHR mean Po of 6.21 ± 1.01 N/cm2 was not different from the mean WKY Po of 6.97 ± 1.64 N/cm2 (p > 0.05); (b) the SHR preparations showed greater shortening for all loads imposed; (c) the SHR Vmax of 0.016 lo/s was greater than the WKY Vmax of 0.013 lo/s (p < 0.05). This study provides evidence that while hypertensive arterial smooth muscle is not able to produce more force than normotensive arterial smooth muscle, it is capable of faster and greater shortening. The latter could result in increased narrowing of hypertensive arteries and increased blood pressure.