bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of quercetin on rat testis aerobic glycolysis
Authors: Trejo Raquel , Valadéz-Salazar Alicia , Delhumeau Graciela
Published: April 2011

Lactate production by testicular fragments and isolated germinal cells at various stages of spermatogenesis was studied in aerobic and anerobic conditions. Several ATPase inhibitors were used to determine the role of ATPase activities in the control of aerobic lactate production. Aerobic glycolysis reached a high level in spermatogonia plus Sertoli cell and in primary spermatocyte populations. The activity was twice that found in early spermatids. Neither Na+–K+ATPase nor mitochondrial F1ATPase seemed to participate directly in the control of aerobic glycolysis. The uncoupling of oxidative phosphorylation revealed the potential role of F1ATPase in providing ADP and Pifor the glycolytic pathway. Lactate production was inhibited by quercetin in all the experimental conditions tested. Quercetin (100 μM) halted lactate production by the Sertoli cell plus spermatogonia population and by isolated primary spermatocytes. In spermatids, quercetin inhibited aerobic glycolysis only by 40%, even at higher concentrations. Only during the first meiotic prophase did quercetin inhibit the activity of a cytosolic Ca2+–Mg2+ATPase. This ATPase was also inhibited by erythro-9-[3-3(hydroxynonyl)]adenine (EHNA), suggesting that a cytoplasmic dynein could be involved in the control of glycolysis in Sertoli cells, spermatogonia, and early primary spermatocytes.Key words: quercetin, aerobic glycolysis, germ cells, cytosolic dynein, mitochondrial ATPase.
Tetanus-induced potentiation of inhibitory postsynaptic potentials in hippooampal CA1 neurons
Authors: Xie Z. , Yip S. , Morishita W. , Sastry B. R.
Published: April 2011

In the present study, tetanus-induced potentiation of inhibitory postsynaptic potentials (IPSPs), previously described by our laboratory, was further investigated in guinea pig hippocampal CA1 neurons. Tetanic stimulation of the stratum radiatum induced a long-term potentiation of the excitatory postsynaptic potential and a potentiation of the γ-aminobutyric acid A (GABAA) receptor mediated fast IPSP without enhancing the GABAB receptor-mediated slow IPSP. During the potentiation, IPSPs evoked by stimulation of the alveus were unaffected. When slices were superfused with DL-2-amino-5-phosphonovaleric acid (an N-methyl-D-aspartate, NMDA, antagonist) and 6-cyano-7-nitroquinoxaline-2,3-dione (a non-NMDA glutamate antagonist), the potentiation of the monosynaptic fast IPSP could still be induced and maintained, suggesting that polysynaptic influences were unnecessary for this process. Finally, since the potentiation was observed in CA1 neurons in which BAPTA or K-252b was injected, this form of plasticity does not appear to be dependent on a rise in intracellular [Ca2+] or protein kinase C (PKC) activity. These results indicate that tetanic stimulation of the stratum radiatum induces a potentiation of GABAergic fast IPSPs in CA1 neurons. The potentiation may be localized to the GABAergic synapse on CA1 neurons.Key words: inhibitory postsynaptic potential, GABAA receptors, N-methyl-D-aspartate receptors, BAPTA, K-252b, hippocampal CA1 neurons.
Functional effects of uridine triphosphate on human skinned skeletal muscle fibers
Authors: Vianna-Jorge R , Oliveira C F , Mounier Y , Suarez-Kurtz G
Published: April 2011

Chemically skinned human skeletal muscle fibers were used to study the effects of uridine triphosphate (UTP) on the tension-pCa relationship and on Ca2+uptake and release by the sarcoplasmic reticulum (SR). Total replacement (2.5 mM) of adenosine triphosphate (ATP) with UTP (i) displaced the tension-pCa relationship to the left along the abcissae and increased maximum Ca2+-activated tension, both effects being larger in slow- than in fast-type fibers; (ii) markedly reduced Ca2+uptake by the SR (evaluated by the caffeine-evoked tension) in both fiber types; (iii) had no effect on the rate of depletion of caffeine-sensitive Ca2+stores during soaking in relaxing solutions; (iv) induced tension in slow- but not in fast-type fibers. The effects on the SR functional properties are consistent with the notion that UTP is a poor substitute for ATP as a substrate for the Ca ATPase pump and as an agonist of the ryanodine-sensitive Ca2+-release channel. The UTP-induced tension in human slow-type fibers is attributed to effect(s) of the nucleotide on the tension-pCa relationship of the contractile machinery. The present data reveal important differences between the effects of UTP on human versus rat muscle fibers.Key words: skinned muscle fiber, UTP-induced tension, tension-pCa relationship, sarcoplasmic reticulum, calcium transport.
Plasma and lipoprotein lipid composition and hepatic antioxidant status in spontaneously hypertensive (SHR) and normotensive (WKY) rats
Authors: Kitts D D , Yuan Y V , Godin D V
Published: April 2011

Plasma and lipoprotein lipid composition and endogenous hepatic antioxidant status were investigated in hypertensive, 14-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Total plasma calcium and magnesium concentrations were similar between both rat strains; however, systolic blood pressure in SHR was greater than in WKY at 13 weeks of age (197 ± 12 vs. 132 ± 14 mmHg; p <= 0.05), confirming hypertension in SHR. Total plasma cholesterol and triacylglycerol concentrations were lower (p <= 0.05) in SHR compared with WKY. A lower (p < 0.05) HDL cholesterol level in SHR plasma resulted in a higher LDL to HDL cholesterol ratio compared with WKY counterparts. No significant differences in the relative proportion of HDL apolipoprotein A-I fraction were observed between SHR and WKY. Both SHR VLDL and HDL triacylglycerol fractions were lower (p < 0.05) in SHR than WKY. Analysis of liver antioxidant enzyme activities showed no differences in rat liver superoxide dismutase (SOD), but lower (p < 0.05) liver glutathione peroxidase (GSH-Px) activity in SHR. However, liver glutathione (GSH) levels were similar in SHR and WKY counterparts. A possible compensatory effect to the oxidative status of SHR was suggested by the significant (p < 0.05) increase in both liver catalase (CAT) and glutathione reductase (GSSG-Red) activities. Despite these results, in vitro oxidative challenge studies with H2O2demonstrated a greater susceptibility of liver to GSH depletion in the SHR, although no parallel change in thiobarbituric acid reactive substances (TBARS) production was observed. The comparatively lower plasma cholesterol observed in hypertensive SHR paralleled specific differences in liver catalase and glutathione redox antioxidant enzyme activities.Key words: liver antioxidant status, plasma and lipoprotein lipids, spontaneously hypertensive rat.
Pattern of c-fos mRNA induction in rat brain by acute morphine
Authors: Gutstein Howard B , Thome Jennifer L , Fine Jeffrey L , Watson Stanley J , Akil Huda
Published: April 2011

Initially, opioid signaling had been thought to be mainly inhibitory in nature. However, it has been shown that opioids can activate specific signaling pathways and induce immediate early gene (IEG) transcription in brain. IEGs can then regulate the transcription of other genes, leading to changes in neuronal function in response to extracellular stimuli. This study was designed to identify brain regions that demonstrate specific induction of the IEG c-fos, a component of the AP-1 transcription factor, in response to acute morphine, and to contrast this induction with the stressful effects of the injection itself. Rats received either 10 mg/kg morphine or an equivalent volume of saline injected subcutaneously. Animals were then sacrificed 15, 30, or 60 min after injection. Specific induction of c-fos mRNA by morphine was seen in dorsomedial caudate-putamen, paraventricular nucleus of the thalamus, central and intralaminar thalamic nuclei, dorsal central grey, superior colliculus, lateral parabrachial nucleus, inferior olivary complex, and caudal nucleus tractus solitarius. These findings represent the first complete anatomical mapping of c-fos induction in rat brain, and show that acute morphine administration alters gene expression in several areas related to known functional properties of opioids. However, regions showing c-fos induction are not all classically associated with opioid receptors and opioid-mediated effects. These findings are considered in the context of the effects of opioids on neural circuitry as well as direct, receptor-mediated effects of morphine on neural cells.Key words: anatomy, immediate early genes, opioids, neural circuitry, nociception, transcriptional regulation.
Similarities and differences of the immune response to exercise and trauma: the IFN-γ concept
Authors: Northoff H , Berg A , Weinstock C
Published: April 2011

Similar to physical fitness, fitness of the immune system requires training. Animals that have been raised under sterile conditions have a poor immune system and fail to thrive. "Immune training" is normally provided by contact with live microorganisms or immunizations. Increasing evidence has suggested that moderate sports can decrease the frequency of infections while excessive, exhausting exercise can lead to the opposite, a situation that has been described by a J-curve. Following prolonged exhausting exercise, a transient partial suppression of several immune functions can be shown, and it has been suggested that this period provides a window for invasion of microbes. On the basis of data showing that endotoxin-inducible interferon-gamma (IFN-gamma) production is virtually abrogated for a short period following excessive exercise, we present the hypothesis that the rigorous regulatory blockade of one of the ways of IFN-gamma induction may be critically involved in causing the transient immunosuppression following exhaustive exercise stress.Key words: exhaustive exercise, immune functions, immunosuppression, interferon-gamma, cytokines.
Glutamine and the effects of exhaustive exercise upon the immune response
Authors: Castell Linda M , Newsholme Eric A
Published: April 2011

There is a high incidence of infections in athletes undergoing intense, prolonged training or participating in endurance races (e.g., the marathon), in particular, upper respiratory tract infections. Prolonged, exhaustive exercise can lower the plasma level of the amino acid, glutamine, which is an important fuel for some cells of the immune system and may have specific immunostimulatory effects. This could therefore be an important factor in the event of an impaired response of immune cells to opportunistic infections. The effects of feeding glutamine to sedentary individuals and to marathon and ultramarathon runners before and after prolonged, exhaustive exercise has been investigated in a series of studies that monitored the incidence of infections and some acute-phase response markers. Oral glutamine, compared with a placebo, appeared to have a beneficial effect on the incidence of infections reported by runners after a marathon.Key words: glutamine, endurance exercise, infections, immune response.
Carteolol is a weak partial agonist on β3-adrenergic receptors in brown adipocytes
Authors: Zhao Jin , Cannon Barbara , Nedergaard Jan
Published: April 2011

The ability of the Beta1/Beta2 partial agonist carteolol to act as an agonist on Beta3-adrenergic receptors was investigated by studying its ability to stimulatethermogenesis (oxygen consumption) in brown fat cells isolated from hamsters. Carteolol wasable to induce thermogenesis, with an EC50 of 5 µM, but it was only a partial(40%) agonist. D,L-Propranolol had a pKB of 5.1 as anantagonist against carteolol in this system, indicating that the carteolol effect was probablymediated via Beta3-receptors. Also in mouse and rat cells, carteolol was a partial agonist withEC50 values around 1 µM. Being a partial agonist, carteolol acted as an antagonistagainst norepinephrine-, BRL-37344-, or CGP-12177-stimulated thermogenesis with apKB of approximately5. The partial agonist effects of carteolol are discussed in relation to the absence of agonisteffect of this compound on guinea-pig taenia cecum Beta3-receptors and in relation to the possible plurality of Beta3-receptors.Key words: carteolol, Beta3-adrenergic receptor, brown fat cells, nonshivering thermogenesis.
Intracardiac iron distribution in newborn guinea pigs following isolated and combined fetal hypoxemia and fetal iron deficiency
Authors: Gulang III Sixto F , Merchant Jennifer R , Eaton Mary A , Fandel Kelly B , Georgieff Michael K
Published: April 2011

Myocardial iron deficiency complicates chronic intrauterine hypoxemia during diabetic pregnancies. To understand the effect of both conditions during fetal life on intracardiac iron prioritization, we measured heart myoglobin, cytochrome c, and elemental iron concentrations in six iron-deficient, hypoxic, five iron-sufficient, hypoxic, six iron-deficient, normoxic, and six iron-sufficient, normoxic newborn guinea pigs. The iron-deficient, hypoxic group had lower heart iron (p = 0.03) but higher myoglobin concentration (p < 0.0001) when compared with the iron-sufficient, normoxic group. The percentage of iron incorporated into myoglobin was higher than control in the iron-deficient, hypoxic group (23.2 ± 7.2% vs. 5.2 ± 0.8%; p < 0.001) and increased as total heart iron decreased (r = 0.97; p < 0.001). In contrast, heart cytochrome c concentration was lower than control in the iron-deficient, hypoxic group (p = 0.01), with equal percentages of heart iron incorporated into cytochrome c. This intracellular prioritization of myocardial iron to myoglobin and away from cytochrome c following combined fetal hypoxemia and iron deficiency may represent an adaptive mechanism to preserve myocardial tissue oxygenation, although at the expense of oxidative phosphorylative capability.Key words: fetal, hypoxia, iron deficiency, myoglobin, cytochrome c, heart.
Developmental changes in synthesis of and responsiveness to prostaglandins I2 and E2 in hypoxic lamb lungs
Authors: de Cléty Stephan Clement , Decell Mary K , Tod Mary L , Sirois Pierre , Gordon John B
Published: April 2011

Previous studies have shown that the attenuated hypoxic pulmonary vasoconstriction (HPV) of young newborn lamb lungs was enhanced by cyclooxygenase inhibition. We sought to determine whether this reflected greater synthesis of and (or) responsiveness to dilator prostaglandins (PG). Protocol 1 measured responses to graded hypoxia and perfusate concentrations of 6-keto-PGF1alpha (the stable metabolite of PGI2) and PGE2 in isolated lungs from 1-day- and 1-month-old lambs. Protocol 2 compared dose responses and segmental vascular resistances during infusion of PGI2 and PGE2 in hypoxic, cyclooxygenase-inhibited, lungs from 1- to 2-day-old and 1- to 3-month-old lambs. Lungs of 1-day-old lambs with attenuated responses to 4% O2 had significantly higher perfusate concentrations of 6-keto-PGF1alpha and PGE2, but responses to both PGE2 and the more potent vasodilator, PGI2 did not differ with age. These data support the hypothesis that attenuated HPV in young newborn lamb lungs is due to increased synthesis of dilator PG, particularly PGI2.Key words : hypoxic pulmonary vasoconstriction, pulmonary vascular development, cyclooxygenase inhibition, segmental vascular resistances.
Voltage-sensitive dye RH421 increases contractility of cardiac muscle
Authors: Cheng Yuanna , Wagoner David R , Mazgalev Todor N , Tchou Patrick J , Efimov Igor R
Published: April 2011

Voltage-sensitive dyes and imaging techniques have proved to be indispensable tools for use in in vitro electrophysiological studies. To avoid motion artifacts in optical recordings, electromechanical uncouplers such as 2,3-butanedione monoxime (BDM) are required. In this study, we sought to determine whether the voltage-sensitive dye RH421 had an effect on the contractility of heart muscle, either alone or in the presence of BDM. Ventricular contractility was studied in (i) isolated rat myocytes and (ii) Langendorff-perfused rat hearts under control conditions, and during perfusion with RH421 or RH421 + BDM. The following results were obtained. (i) The amplitude of cell shortening increased progressively from 6.24 ± 0.64 to 9.95 ± 1.02 µm during 15 min of superfusion with 5 µM RH421 (n = 11), and further increased to 12.54 ± 0.97 µm during washout. In seven cells first perfused with 15 mM BDM and then with 15 mM BDM + 5 µM RH421, the amplitude of the cell shortening first decreased from 5.17 ± 0.51 to 0.41 ± 0.19 µm, then the amplitude increased to 2.63 ± 0.25 µm. (ii) Left ventricular pressure (LVP) of the heart (n = 7) was reduced by 15 mM BDM from 60.7 ± 2.5 to 2.8 ± 0.5 mmHg (1 mmHg = 133.3 Pa). LVP increased to 12.8 ± 1.1 mmHg during subsequent perfusion with 10 µM RH421 in the presence of BDM and did not change (LVP = 12.4 ± 2.4 mmHg) during washout of the dye. Therefore, RH421 increased the contractility of rat hearts and isolated myocytes with and without BDM.Key words: voltage-sensitive dye RH421, 2,3-butanedione monoxime, left ventricular pressure, cell shortening, contractility.
Simultaneous production of carbon monoxide and thiobarbituric acid reactive substances in rat tissue preparations by an iron-ascorbate system
Authors: Vreman Hendrik J , Wong Ronald J , Sanesi Catherine A , Dennery Phyllis A , Stevenson David K
Published: April 2011

Most of the carbon monoxide (CO) produced by mammals is a product of the heme oxygenase (HO) reaction, the rate-limiting step in the heme degradation pathway leading to the generation of bilirubin in man. However, some CO is derived from other sources. We studied the association of CO production with lipid peroxidation in tissue preparations from adult male Wistar rats. Supernatants, from 20% tissue homogenates in potassium phosphate buffer, centrifuged for 1 min at 13 000 × g, were incubated for 30 min at 37°C in septum-sealed vials in the dark with ascorbate (100 µM) and Fe(II) (6 µM) and (or) Fe(III) (60 µM). Butylated hydroxytoluene (BHT, 100 µM) was added for the blank reaction. CO produced into the headspace was quantitated by gas chromatography. Thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), and lipid hydroperoxides (LOOH) in the reaction medium were quantitated by spectrophotometry. Of the tissues studied, CO and TBARS formation was greatest for brain, followed by kidney, lung, spleen, and blood, but no CO or TBARS formation was detected for testes, intestine, liver, and heart. Cell fractionation studies indicated that these differences might be due to the presence of endogenous soluble antioxidants in the latter tissues. Furthermore, these studies demonstrated that CO was exclusively generated by subcellular fractions that contained membranes. The magnitude of the rate of product formation in brain supernatants depended on the concentration of Fe(II) and (or) Fe(III). The formation of CO, TBARS, CD, and LOOH increased linearly with time for up to 30 min, but the rates of product formation were different. Product formation was completely inhibited by BHT (100 µM), biliverdin (50 µM), bilirubin (50 µM), citrate (100 µM), and the Fe(II) chelators, desferrioxamine mesylate (100 µM) and diethylenetriaminepentaacetate, but not by 10 µM of the HO inhibitor, zinc deuteroporphyrin bis glycol. We conclude that CO generation is associated with the process of in vitro lipid peroxidation in tissues with limited antioxidant reserves.Key words: brain, carbon monoxide, conjugated dienes, lipid peroxidation, thiobarbituric acid reactive substances (TBARS).
Rapid insulin sensitivity test (RIST)
Authors: Lautt W Wayne , Wang Xiaowsi , Sadri Parissa , Legare Dallas J , Macedo M Paula
Published: April 2011

A rapid insulin sensitivity test (RIST) was recently introduced to assess insulin action in vivo (H. Xie, L. Zhu, Y.L. Zhang, D.J. Legare, and W.W. Lautt. J. Pharmacol. Toxicol. Methods, 35: 77-82. 1996). This technical report describes the current recommended standard operating procedure for the use of the RIST in rats based upon additional experience with approximately 100 tests. We describe the manufacture and use of an arterial-venous shunt that allows rapid multiple arterial samples and intravenous administration of drugs. The RIST procedure involves determination of a stable arterial glucose baseline to define the ideal euglycemic level to be maintained following a 5-min infusion of insulin, with the RIST index being the amount of glucose required to be infused to maintain euglycemia over the test period. Insulin administration by a 5-min infusion is preferable to a 30-s bolus administration. No significant difference was determined between the use of Toronto pork-beef or human insulin. Four consecutive RISTs were carried out in the same animal over 4-5 h with no tendency for change with time. The RIST index is sufficiently sensitive and reproducible to permit establishment of insulin dose-response curves and interference of insulin action by elimination of hepatic parasympathetic nerves, using atropine. This technical report provides the current recommended standard operating procedure for the RIST.Key words: insulin, resistance, test, methodology, glucose.
Effects of propentofylline on adenosine receptor activity in Chinese hamster ovary cell lines transfected with human A1, A2A, or A2B receptors and a luciferase reporter gene
Authors: Borgland Stephanie L , Castañón Maria , Spevak Walter , Parkinson Fiona E
Published: April 2011

Propentofylline is neuroprotective in vivo, but its mechanism of action is not completely understood. Previously, propentofylline was shown to block adenosine transport processes, to inhibit three adenosine receptor subtypes, and to inhibit cAMP phosphodiesterase. We tested the effect of propentofylline on adenosine receptor function in Chinese hamster ovary (CHO) cells transfected with human adenosine A1, A2A, or A2B receptors and a luciferase reporter gene under control of a promoter sequence containing several copies of the cAMP response element. We investigated the concentration-dependent inhibitory effects of propentofylline on cAMP phosphodiesterase, adenosine transport processes, and adenosine A1, A2A, and A2B receptors. At concentrations >= 1 mM, propentofylline increased luciferase activity probably as a result of inhibition of cAMP phosphodiesterase. Inhibition of [3H]adenosine uptake by propentofylline was concentration dependent, with IC50 values of 37-39 µM for the three cell types. Agonist-activated adenosine A1 receptors were antagonized by 100 µM propentofylline, but inhibition of agonist-stimulated A2A or A2B receptors was not observed. In contrast, A1 and A2A receptor mediated effects of adenosine were enhanced by propentofylline at concentrations of 1 and 100 µM, respectively. These data indicate that the net effects of propentofylline in vivo will be dependent on the concentrations of propentofylline and adenosine available and on the subtypes of adenosine receptors, phosphodiesterases, and nucleoside transporters present.Key words: adenosine receptors, nucleoside transport, propentofylline.
Estrogen replacement increases coronary artery distensibility in ovariectomized rats
Authors: Zhang Yunlong , Davidge Sandra T
Published: April 2011

The effect of estrogen on the passive characteristics of arteries is not known. We hypothesized that estrogen would increase arterial distensibility as part of its protective effect on the vasculature. Female Sprague-Dawley rats were ovariectomized at 11 weeks of age. One group received a placebo (n = 6), while two other groups (n = 5 each) of rats received a 17β-estradiol pellet (0.15 mg or 0.5 mg with 60-day release). After 4 weeks of estrogen replacement, coronary and mesenteric arteries (<200 µm diameter) were dissected and mounted on a dual-chamber arteriograph. Lumen diameter and wall thickness were measured in pressurized arteries. The relative changes in diameter (distensibility) as well as wall thickness per unit change in pressure were significantly increased (p < 0.05) in the coronary arteries of the 0.5 mg estradiol replaced rats compared with the ovariectomized control animals and the 0.15 mg estradiol replaced rats. Surprisingly, in the mesenteric arteries from the same animals, there was no difference in distensibility or pressure - wall thickness among the groups. This study provides experimental data of a novel hypothesis that estrogen may afford part of its protection through vascular remodeling of the coronary circulation.Key words: vasculature, remodeling, cardiovascular disease.
Galactose transport inhibition by cytochalasin E in rat intestine in vitro
Authors: Díez-Sampedro Ana , Urdaneta Elena , Lostao M Pilar , Barber Ana
Published: April 2011

Cytochalasins are cytoskeleton disrupters, and cytochalasin E has been reported to increase intestinal paracellular permeability. In this study, the cytochalasin E effect on galactose transport has been investigated. Ussing-type chamber experiments show an inhibitory effect of 20 µM cytochalasin E on unidirectional mucosal to serosal flux of galactose. On the contrary, the opposite unidirectional flux is not modified by the inhibitor. Results using intestinal everted sacs and rings confirm that galactose uptake by the tissue is diminished by cytochalasin E. The effect appears already after 5 min incubation, depends on cytochalasin E concentration, and does not occur in the absence of Na+. The inhibition is accompanied by an increase in the apparent Kmof the active sugar transport (11.5 vs.15.8 mM) without significant change in the Vmax(10.6 vs. 9.1 µmol·g-1wet weight·5 min-1). Cytochalasin E does not modify either galactose uptake by brush border membrane vesicles or Na+-K+ATPase activity in the enterocytes, indicating that the inhibitory effect on the Na+-dependent sugar transport cannot be explained as a direct effect on SGLT1 activity or as an indirect effect through the Na+-K+ATPase. Thus, our results suggest that cytochalasin E decreases SGLT1 activity indirectly through cytoskeleton disruption.Key words: cytochalasin E, intestinal absorption, cytoskeleton.
Characterization of positive inotropic effect of colforsin dapropate hydrochloride, a water-soluble forskolin derivative, in isolated adult rat cardiomyocytes
Authors: Miyake Rikako , Yoshida Hiroyuki , Tanonaka Kouichi , Miyamoto Yuki , Hayashi Hideharu , Kajiwara Hiroshi , Takeo Satoshi
Published: April 2011

The present study was undertaken to characterize the positive inotropic action of colforsin dapropate hydrochloride (NKH477), a novel water-soluble forskolin derivative, on isolated cardiomyocytes of adult rats. Simultaneous measurements of cellular contraction and intracellular calcium concentration ([Ca2+]i) were carried out. The effects of isoprenaline and ouabain on these parameters were also determined for comparison. The contraction and maximum [Ca2+]iof NKH477-, isoprenaline-, or ouabain-treated cells were increased concentration dependently. Peak shortening of NKH477-treated cells was positively correlated with the shortening velocity and inversely with the time to peak shortening. Maximum, but not minimum, [Ca2+]iin NKH477-treated cells was correlated with the rate of increase in [Ca2+]iand inversely with the time to maximum [Ca2+]i. Similar results were obtained with isoprenaline. In contrast, ouabain increased both maximum and minimum [Ca2+]i. Treatment with either NKH477 or isoprenaline increased cellular cAMP content, but treatment with ouabain did not. These results suggest that the positive inotropic action of NKH477 is associated with an increase in [Ca2+]iand acceleration of its kinetics.Key words: adenylate cyclase, calcium transient, colforsin dapropate, isoprenaline, ouabain.
An intragastric amino acid mixture influences extracellular amino acid profiles in the lateral hypothalamic area of freely moving rats
Authors: Choi Yang-Ho , Chang Nancy , Anderson G Harvey
Published: April 2011

We tested the effect of equicaloric loads of glucose (0.89 g) or a balanced amino acid mixture (0.85 g) on extracellular amino acid concentrations in the brains of freely moving rats. At 15:30 hours, the microdialysis probe was inserted into the lateral hypothalamic area of ambulatory rats, and food and water were removed. Dialysates were collected every 20 min from 1 h prior to gavage (18:00 hours) and until 3 h after the gavage. Amino acid concentrations in the dialysate were determined by reverse-phase HPLC. Following the amino acid gavage, extracellular amino acid concentrations significantly increased from baseline for alanine, isoleucine, leucine, methionine, threonine, tyrosine, and valine. Those elevations occurred within 20-40 min following the amino acid load, and lasted up to 100 min. After the glucose and water treatments, amino acid concentrations were either not affected or gradually diminished from baseline. We conclude that extracellular amino acid concentration in the lateral hypothalamus is influenced by the composition of food consumed.Key words: blood-brain barrier, food intake, glucose, microdialysis, protein.
Cytosolic fatty acid binding protein enhances rat hepatocyte [3H]palmitate uptake
Authors: Burczynski F J , Fandrey S , Wang G , Pavletic P A , Gong Y
Published: April 2011

Liver cytosolic fatty acid binding protein (FABP) represents the intracellular equivalent to extracellular serum albumin, participating in the intracellular transport of long-chain fatty acids. In this study we observed the effect of increasing and decreasing FABP levels on hepatocyte [3H]palmitate uptake in male Sprague-Dawley rats. We also were interested to determine whether uptake, from either the unbound or unbound and protein-bound fractions, was fundamentally different at the different FABP levels. FABP levels were modified by hypophysectomy and clofibrate treatment (50 mg/100 g body weight for 10 days). Results showed that the [3H]palmitate clearance rates paralleled the 54% decrease and 73% increase in FABP levels in hypophysectomy and clofibrate-treated animals, respectively. In the presence of 2 and 20 µM albumin, hepatocyte clearance rates of unbound [3H]palmitate from hypophysectomized animals (0.16 ± 0.01 and 0.64 ± 0.01 mL·s-1·10-6cells, respectively) were significantly lower (p < 0.01) than those of the sham group (0.30 ± 0.02 and 1.00 ± 0.06 mL·s-1·10-6cells, respectively). However, the unbound [3H]palmitate clearance rates from the clofibrate-treated group (0.39 ± 0.04 and 1.18 ± 0.12 mL·s-1·10-6cells) were significantly higher (p < 0.01) than the control group (0.29 ± 0.02 and 0.81 ± 0.05 mL·s-1·10-6cells) for 2 and 20 µM albumin, respectively. To investigate whether uptake was fundamentally different between the hypophysectomized and clofibrate-treated groups, we expressed the clearance rates as enhancement factors, i.e., EF = CL20µM/CL2µM. No statistical difference was observed between EF of the hypophsectomized (3.8 ± 0.4) and EF of the clofibrate-treated (3.1 ± 0.3) groups, suggesting that the extracted ligand originated from similar fractions.Key words: palmitic acid, albumin, growth hormone, liver, fatty acid binding protein, uptake, hepatic, long-chain fatty acids, clofibrate, hypophysectomy.
Functional role of local angiotensin-converting enzyme (ACE) in adrenal catecholamine secretion in vivo
Authors: Yamaguchi Nobuharu , Martineau Daniel , Lamouche Stéphane , Briand Richard
Published: April 2011

The aim of the present study was to investigate whether exogenous angiotensin I (AngI) is locally converted to angiotensin II (AngII), which in turn results in an increase in the adrenal catecholamine (CA) secretion in the adrenal gland in anesthetized dogs. Plasma CA concentrations in adrenal venous and aortic blood were determined by an HPLC-electrochemical method. Adrenal venous blood flow was measured by gravimetry. Local administration of AngI (0.0062 to 6.2 µg, 0.0096 to 9.6 µM) to the left adrenal gland resulted in significant increases in CA output in a dose-dependent manner. Following administration of 0.62 µg (0.96 µM) of AngI, adrenal epinephrine and norepinephrine outputs increased from 20.8 ± 13.6 to 250.9 ± 96.4 ng·min-1·g-1 (p < 0.05, n = 5) and from 2.8 ± 1.7 to 29.6 ± 11.1 ng·min-1·g-1 (p < 0.05, n = 5), respectively. From the same left adrenal gland, the output of AngII increased from -0.02 ± 0.04 to 26.39 ± 11.38 ng·min-1·g-1 (p < 0.05, n = 5), while plasma concentrations of AngII in aortic blood remained unchanged. In dogs receiving captopril (12.5 µg, 0.5 mM) 10 min prior to AngI, the net amounts of CA and AngII secreted during the first 3 min after AngI were diminished by about 80% (p < 0.05, n = 5) compared with those obtained from the control group. There was a close correlation (r2 = 0.91, n = 6) between the net increases in AngII and CA outputs induced by AngI. The results indicate that the local angiotensin converting enzyme is functionally involved in regional AngII formation in the canine adrenal gland in vivo. The study suggests that AngII thus generated may play a role in the local regulation of adrenal CA secretion.Key words: angiotensin I, angiotensin II, captopril, adrenal gland, anesthetized dog.
Effect of hyperoxia and hypoxia on leg blood flow and pulmonary and leg oxygen uptake at the onset of kicking exercise
Authors: MacDonald Maureen J , Tarnopolsky Mark A , Hughson Richard L
Published: April 2011

The purpose of this study was to examine the interactions of adaptations in O2 transport and utilization under conditions of altered arterial O2 content (CaO2), during rest to exercise transitions. Simultaneous measures of alveolar ([Formula: see text]O2alv) and leg ([Formula: see text]O2mus) oxygen uptake and leg blood flow (LBF) responses were obtained in normoxic (FiO2 (inspired fraction of O2) = 0.21), hypoxic (FiO2 = 0.14), and hyperoxic (FiO2 = 0.70) gas breathing conditions. Six healthy subjects performed transitions in leg kicking exercise from rest to 48 ± 3 W. LBF was measured continuously with pulsed and echo Doppler ultrasound methods, [Formula: see text]O2alv was measured breath-by-breath at the mouth and [Formula: see text]O2mus was determined from LBF and radial artery and femoral vein blood samples. Even though hypoxia reduced CaO2 to 175.9 ± 5.0 from 193.2 ± 5.0 mL/L in normoxia, and hyperoxia increased CaO2 to 205.5 ± 4.1 mL/L, there were no differences in the absolute values of [Formula: see text]O2alv or [Formula: see text]O2mus across gas conditions at any of the rest or exercise time points. A reduction in leg O2 delivery in hypoxia at the onset of exercise was compensated by a nonsignificant increase in O2 extraction and later by small increases in LBF to maintain [Formula: see text]O2mus. The dynamic response of [Formula: see text]O2alv was slower in the hypoxic condition; however, hyperoxia did not affect the responses of oxygen delivery or uptake at the onset of moderate intensity leg kicking exercise. The finding of similar [Formula: see text]O2mus responses at the onset of exercise for all gas conditions demonstrated that physiological adaptations in LBF and O2 extraction were possible, to counter significant alterations in CaO2. These results show the importance of the interplay between O2 supply and O2 utilization mechanisms in meeting the challenge provided by small alterations in O2 content at the onset of this submaximal exercise task.
Nitric oxide inhibits norepinephrine-induced hepatic vascular responses but potentiates hepatic glucose output
Authors: Ming Zhi , Han Chao , Lautt W Wayne
Published: April 2011

We previously reported that sympathetic nerve-induced vasoconstriction in the intestine resulted in shear stress induced release of nitric oxide (NO) that led to presynaptic inhibition of transmitter release. In contrast, studies in the liver suggested a postsynaptic inhibition of vascular responses, thus leading to the hypothesis tested here that maintained catecholamine release in the liver would result in maintained metabolic catecholamine action in the face of inhibition of vascular responses. In rats, norepinephrine (NE) induced elevations in arterial glucose content were inhibited by NO synthase antagonism (Nω-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg, intraportal) but potentiated by NO donor administration (3-morpholinosydnonimine (SIN-1), 0.2 mg/kg, intraportal). The potentiated effect of SIN-1 was abolished by indomethacin (7.5 mg/kg, intraportal). To confirm the hepatic site of metabolic effect, cats were used so that blood flow and hepatic glucose balance could be determined. SIN-1 potentiated NE-induced glucose output from the liver from 5.0 ± 0.4 to 7.2 ± 0.6 mg·min-1·kg-1. The potentiation was blocked by methylene blue, a guanylate cyclase inhibitor. Contrary to the glucose response, L-NAME potentiated but SIN-1 attenuated NE-induced portal vasoconstriction. Thus NO is shown to produce differential modulation of vascular and metabolic effects of NE. Vasoconstriction of the hepatic vasculature is inhibited by NO, whereas the glycogenolytic response to NE is potentiated, responses that are probably mediated by prostaglandin.Key words: prostaglandin, glucose, portal vasculature, Nω-nitro-L-arginine methyl ester, 3-morpholinosydnonimine.
Pharmacology and quantitative structure-activity relationships of imidazolylpropylguanidines with mepyramine-like substructures as non-peptide neuropeptide Y Y1receptor antagonists
Authors: Dove Stefan , Michel Martin C , Knieps Sebastian , Buschauer Armin
Published: April 2011

The design of non-peptide, Y1-selective antagonists of neuropeptide Y (NPY) as pharmacological tools is in progress and is increasingly important as therapeutic applications are expected. Starting from the potent histamine H2agonist and weak NPY Y1antagonist arpromidine, 16 imidazolylpropylguanidine derivatives were synthesized and tested for Y1antagonistic activity (inhibition of NPY-stimulated Ca2+increase in human erythroleukemic cells), where the pheniramine-like moiety of arpromidine was replaced with 2-pyridylaminoalkyl, benzyl-(2-pyridyl)aminoalkyl, and phenyl-(2-pyridyl)alkylaminoalkyl partial structures derived from mepyramine. The pA2values of the most active compounds are in the range of 6.2-6.5. Quantitative structure-activity relationships (QSAR) were investigated by fragment regression analysis. Results indicate that a tetramethylene spacer between the guanidino group and the amino nitrogen is optimal. For an at least moderate degree of Y1antagonistic activity, a second benzyl or phenyl group must be present in addition to the 2-pyridyl ring. At this second group, hydrophobic substituents such as 3,4-di-Cl and 4-Br further enhance Y1antagonism. The most active derivative additionally bears a 5-Br substituent at the 2-pyridyl moiety. Structure-activity relationships suggest that the compounds might be able to partially imitate the role of NPY when interacting with Y1receptors and thus behave as moderate non-peptide NPY Y1antagonists.Key words : neuropeptide Y Y1antagonists, imidazolylpropylguanidines, quantitative structure-activity relationships.
Opposite change with ischaemia in the antifibrillatory effects of class I and class IV antiarrhythmic drugs resulting from the alteration in ion transmembrane exchanges related to depolarization
Authors: Aupetit Jean-François , Bui-Xuan Bernard , Kioueh Idriss , Loufoua Joseph , Frassati Dominique , Timour Quadiri
Published: April 2011

It is known that class I antiarrhythmic drugs lose their antifibrillatory activity with severe ischaemia, whereas class IV antiarrhythmic drugs acquire such activity. Tachycardia, which is also a depolarizing factor, has recently been shown to give rise to an alteration of ion transmembrane exchanges which is particularly marked in the case of calcium. This leads one to wonder if the change in antifibrillatory activity of antiarrhythmic drugs caused by ischaemia depends on the same process. The change in antifibrillatory activity was studied in normal conditions ranging to those of severe ischaemia with a class I antiarrhythmic drug, flecainide (1.00 mg·kg-1 plus 0.04 mg·kg-1·min-1), a sodium channel blocker, and a class IV antiarrhythmic drug, verapamil (50 µg·kg-1 plus 2 µg·kg-1·min-1), a calcium channel blocker. The experiments were performed in anaesthetized, open-chest pigs. The resulting blockade of each of these channels was assessed at the end of ischaemic periods of increasing duration (30, 60, 120, 180, 300, and 420 s) by determining the ventricular fibrillation threshold (VFT). VFT was determined by means of trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode introduced into the myocardium (heart rate 180 beats per min). Ischaemia was induced by completely occluding the left anterior descending coronary artery. The monophasic action potential was recorded concurrently for the measurement of ventricular conduction time (VCT). The monophasic action potential duration (MAPD) varied with membrane polarization of the fibres. The blockade of sodium channels by flecainide, which normally raises VFT (7.0 ± 0.4 to 13.8 ± 0.8 mA, p < 0.001) and lengthens VCT (28 ± 3 to 44 ± 5 ms, p < 0.001), lost its effects in the course of ischaemia. This resulted in decreased counteraction of the ischaemia-induced fall of VFT and decreased aggravation of the ischaemia-induced lengthening of VCT. The blockade of calcium channels, which normally does not alter VFT (between 7.2 ± 0.6 and 8.4 ± 0.7 mA, n.s.) or VCT (between 30 ± 2 and 34 ± 3 ms, n.s.), slowed the ischaemia-induced fall of VFT. VFT required more time to reach 0 mA, thus delaying the onset of fibrillation. Membrane depolarization itself was opposed as the shortening of MAPD and the lengthening of VCT were also delayed. Consequently there is a progressive decrease in the role played by sodium channels during ischaemia in the rhythmic systolic depolarization of the ventricular fibres. This reduces or suppresses the ability of sodium channel blockers to act on excitability or conduction, and increases the role of calcium channel blockers in attenuating ischaemia-induced disorders.Key words: pigs, ion transmembrane exchanges, myocardial ischaemia, sodium channel, calcium channel.
Cardiovascular α1-adrenoceptor subtypes: functions and signaling
Authors: Varma Daya R , Deng Xing-Fei
Published: April 2011

α1-Adrenoceptors (α1AR) are G protein-coupled receptors and include α1A, α1B, and α1Dsubtypes corresponding to cloned α1a, α1b, and α1d, respectively. α1AR mediate several cardiovascular actions of sympathomimetic amines such as vasoconstriction and cardiac inotropy, hypertrophy, metabolism, and remodeling. α1AR subtypes are products of separate genes and differ in structure, G protein-coupling, tissue distribution, signaling, regulation, and functions. Both α1AAR and α1BAR mediate positive inotropic responses. On the other hand, cardiac hypertrophy is primarily mediated by α1AAR. The only demonstrated major function of α1DAR is vasoconstriction. α1AR are coupled to phospholipase C, phospholipase D, and phospholipase A2; they increase intracellular Ca2+and myofibrillar sensitivity to Ca2+and cause translocation of specific phosphokinase C isoforms to the particulate fraction. Cardiac hypertrophic responses to α1AR agonists might involve activation of phosphokinase C and mitogen-activated protein kinase via Gq. α1AR subtypes might interact with each other and with other receptors and signaling mechanisms.Key words: cardiac hypertrophy, inotropic responses, central α1-adrenoreceptors, arrythmias.
Relationship between vanadate induced relaxation and vanadium content in guinea pig taenia coli
Authors: Mochizuki Mariko , Ueda Fukiko , Sano Tadashi , Hondo Ryo
Published: April 2011

Vanadate has been known to induce a transient increase in high K+induced contraction, and also gradually relax the high K+contraction itself in guinea pig taenia coli. The relationship between the rate of relaxation and ion content of Na+, K+, and V ion at the cellular level was investigated when vanadate was applied to contracted muscle. Tissue Na+and V ion content increased linearly, depending on the time after vanadate treatment, reaching maximum levels of approximately 50 mM·kg-1and 0.25 mM·kg-1wet weight, respectively. There was a positive correlation between the V ion and Na+contents, while there was a negative correlattion between both ions and the relaxed rate of the high K+induced contraction. The uptake of V ion was affected by the external K+concentration, and the maximum rate of V ion uptake decreased to 40% in the presence of 90 mM external K+. These results suggest that a small amount of V ion was enough to inhibit the Na+pump activity and muscle contraction in the high K+solution.Key words: vanadate, high K+, relaxation, taenia coli, vanadium.
Fenofibrate lowers blood pressure in two genetic models of hypertension
Authors: Shatara Raied Khaled , Quest Dale W , Wilson Thomas W
Published: April 2011

Fenofibrate, a commonly used lipid lowering drug, induces the expression of the gene coding for cytochrome P450-4A, whose major product is 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE, a potassium channel antagonist, could increase or decrease blood pressure (BP). We studied the effects of four weeks of oral fenofibrate on BP, urine output (UVol), plasma renin activity (PRA), and urine protein excretion in young (4-5 weeks) stroke prone spontaneously hypertensive rats (SHRSP), older (25 weeks) SHRSP, Dahl salt sensitive rats (Dahl S) on a high salt diet, Dahl S rats on a normal salt diet, and normotensive Sprague-Dawley (SD) rats. Fenofibrate prevented the increase in BP in 4-5 week old SHRSP, reduced BP in 25 week old SHRSP, but had no effect on BP in normotensive SD rats. Similarly, fenofibrate prevented the increase in BP in Dahl S rats on a high salt diet, but had no effect in Dahl S rats on a low salt diet. Fenofibrate increased UVol (and reduced weight gain) in young SHRSP and tended to increase it in other groups. It also increased PRA 2 to 5-fold in all groups except older SHRSP. Young SHRSP receiving fenofibrate excreted significantly less urine protein than control rats. The drug reduced proteinuria in Dahl S rats on high salt diet, but had no significant effect on proteinuria in other groups. In summary, fenofibrate reduced blood pressure and weight gain, increased UVol and PRA, and reduced urine protein excretion in young SHRSP. Other groups of animals showed these changes to a variable, but directionally similar extent. These findings are consistent with a natriuretic effect of fenofibrate.

Key words: hypertension, animal models, natriuresis, fenfibrate, lipid lowering agents.
Measuring sexual size dimorphism in the yellow-pine chipmunk (Tamias amoenus)
Authors: Schulte-Hostedde Albrecht I , Millar John S
Published: April 2011

Body size was examined in the yellow-pine chipmunk (Tamias amoenus), which is reported to have female-biased sexual size dimorphism. Our objective was to determine if yellow-pine chipmunks from the Kananaskis Valley were dimorphic. Three methods were used. We compared body mass, 5 univariate components of body size, and multivariate centroids between males and females, and quantified measurement error. Females were significantly heavier (10-20%) and had a longer body (4%) and a longer (0.9%) and wider (2.2%) skull than male chipmunks, as well as being larger in overall size of skeletal tissue (structural body size). Multivariate methods such as discriminant functional analysis can robustly determine whether the sexes are significantly different in overall structural body size. However, univariate measures of body size provide an intuitively clear index of the magnitude of the difference in size of a particular character between the sexes.