bluuebunny/crossref_metadata_2025 huggingface dataset:
K+ ion regulation in retina
Authors: Reichenbach Andreas , Henke Andre , Eberhardt Wolfgang , Reichelt Winfried , Dettmer Dietrich
Published: April 2011

During onset and offset of illumination, considerable changes in extracellular K+ concentration ([K+]e) occur within particular retinal layers. There are two ways in which glial cells may control [K+]e: (1) by space-independent processes, for example, by K+ uptake due to the Na+–K+ ATPase, and (2) by space-dependent processes, that is, by spatial buffering currents flowing through K+ channels. Rabbit retinal Müller (glial) cells were studied for expression of mechanisms supporting both kinds of processes. This review demonstrates that rabbit Müller cells have Na–K pumps whose distribution and properties are highly adapted to meet the needs of efficient K+ clearance. Furthermore, spatial buffering currents through specialized K+ channels of Müller cells greatly accelerate retinal K+ clearance during and after stimulation.Key words: glia, retina, potassium clearance, sodium–potassium pump, potassium channels.
Role of Na/K/Cl cotransport in astrocytes
Authors: Walz Wolfgang
Published: April 2011

The kinetic characterization of the Na/K/Cl cotransport of cultured astrocytes and evidence for its involvement in volume regulation and K+ net uptake during K+ clearance are reviewed. Emphasis is put on experimental evidence for a proposed sodium cycle in astrocytes; this cycle involves a Na+–K+ ATPase that is stimulated by both a high external K+ and intracellular Na+. Elevated external K+ also stimulates the Na/K/Cl carrier, transporting these ions inward. As a result Na+ is cycled across the membrane, carried inward by the Na/K/Cl carrier, and returned by the Na+–K+ ATPase. Both functionally coupled mechanisms lead to intracellular KCl accumulation and inward movements of water to compensate for increased osmolarity. The combined cycle is expected to play a major role in the regulation of physiological K+ levels in the brain.Key words: furosemide, ion homeostasis, Na+–K+ ATPase, swelling, volume regulation.
Microsomal cytochrome P450 1A1 dependent monooxygenase activity in guinea pig heart: induction, inhibition, and increased activity by addition of exogenous NADPH–cytochrome P450 reductase
Authors: McCallum Gordon P. , Horton Jennifer E. , Falkner K. Cameron , Bend John R.
Published: April 2011

Characterization of cytochrome P450 1A1 dependent monooxygenases in guinea pig heart revealed low rates of 7-ethoxyresorufin O-deethylation, which are markedly increased (20-fold) by treatment with β-naphthoflavone, a poly cyclic aromatic hydrocarbon. Both 7-ethoxyresorufin O-deethylation and 7-methoxyresorufin O-demethylation were found to be approximately 4-fold higher in microsomes prepared from the ventricle than the atrium of β-naphthoflavone-induced guinea pigs. The low rates of 7-ethoxyresorufin O-deethylation in cardiac microsomes were due, at least in part, to a deficiency of the flavoprotein NADPH–cytochrome P450 reductase; addition of exogenous NADPH–cytochrome P450 reductase dramatically increased 7-ethoxyresorufin O-deethylation in cardiac microsomes of guinea pigs, before and after treatment with β-naphthoflavone. N-Benzyl-1-aminobenzotriazole, a suicide substrate of cytochrome P450 1A1 in guinea pig, was able to inhibit almost all of the 7-ethoxyresorufin O-deethylase and 7-methoxyresorufin O-demethylase activities in polycyclic aromatic hydrocarbon induced guinea pig heart (88 and 71%, respectively), suggesting that cytochrome P450 1A1 coupled to NADPH–cytochrome P450 reductase in these microsomes inactivates itself by a suicidal mechanism. Addition of α-naphthoflavone, an inhibitor of cytochrome P450 1A isozymes, to cardiac microsomes from β-naphthoflavone-induced guinea pigs resulted in greater than 95% inhibition of 7-ethoxyresorufin O-deethylase activity. The biological significance of these low levels of cytochrome P450 1A1 monooxygenase activity in guinea pig heart and their induction by polycyclic aromatic hydrocarbons are not currently understood.Key words: guinea pig, heart, cytochrome P450, NADPH–cytochrome P450 reductase, polycyclic aromatic hydrocarbon.
High percentage of skew-distributed miniature endplate currents in old mice
Authors: Vautrin J. , Kriebel M. E.
Published: April 2011

Muscle fibers from diaphragms of old (14 to 24 months) and young adult (1 to 2 months) inbred (strain C57BL/6) mice were voltage clamped at −140 mV with two microelectrodes near the neuromuscular junction. Miniature endplate currents (MEPCs) were digitized so that peak amplitudes and rise times could be determined. MEPC amplitude distributions from old mice varied greatly between fibers from the same diaphragm, and the mean MEPC amplitude (2.1 ± 0.83 nA, mean ± SD) was smaller than in young mice (5.2 ± 0.59 nA). In old mice, some (50%) amplitude distributions were bell shaped, composed of mainly bell-MEPCs with a 2- to 5-nA mode, whereas others (30%) were skewed with a 0.5- to 2-nA mode, and some (20%) showed two peaks, representing both skew- and bell-MEPC classes. MEPC rise-time distributions from old mice varied between fibers, although they all had similar modes. Some (30%) were bell shaped (similar to those in young mice) with a mode between 0.5 and 1 ms (coefficient of variation, 40%), but most distributions were skewed. Endplates with smaller mean MEPC amplitudes showed a longer mean rise time, and for a given junction, MEPC amplitudes were correlated positively to the corresponding rise times. This observation, together with analyses of the rising phases, indicates that MEPCs with long rise times were not generated at remote sites. We discuss our results with regard to the hypothesis of a dynamic formation of transmitter packets, and we attribute long rise time, skew-MEPCs to a prolonged release process. During aging, the state of release that generates the skew-MEPC class appears more dominant than the state generating the bell-MEPC class.Key words: synaptic transmission, aging, miniature endplate potential, quantal release, neuromuscular junction, quantal subunit.
Na+–K+ ATPase concentration in different adult rat skeletal muscles is related to oxidative potential
Authors: Chin E. R. , Green H. J.
Published: April 2011

To investigate the relationship among fibre type, oxidative potential, and Na+–K+ ATPase concentration in skeletal muscle, adult male Wistar rats weighing 259 ± 8 g [Formula: see text] were sacrificed and the soleus (SOL), extensor digitoram longus (EDL), red vastus lateralis (RV), and white vastus lateralis (WV) removed. These muscles were chosen as being representative of the two major fibre type populations: slow twitch (SOL) and fast twitch (EDL, RV, WV) and exhibiting either a high (SOL, EDL, RV) or low (WV) oxidative potential. Na+–K+ ATPase concentration (pmol∙g−1 wet weight), measured by the [3H]ouabain binding technique, differed (p < 0.01) only between the WV (238 ± 7.9) and the SOL (359 ± 9.6), EDL (365 ± 10), and RV (403 ± 12). Similarly, muscle oxidative potential as measured by the maximal activity of citrate synthase was different (p < 0.01) only between the WV and the other three muscles. Citrate synthase activity (μmol∙min−1∙g−1 wet weight) was 4.0 ± 0.7, 12.3 ± 0.9, 9.1 ± 0.7, and 11.3 ± 1.0 in the WV, SOL, EDL, and RV, respectively. These results indicate that Na+–K+ ATPase concentration is not related to the speed of contraction but to the oxidative potential of the muscle. Since chronic activity is a primary determinant of oxidative potential, it would be expected that increases in Na+–K+ ATPase would accompany increases in muscle utilization.Key words: Na+–K+ ATPase, citrate synthase, type I and type II fibres.
Blood pressure normalization in carotid barodenervated rats: role of cardiac output
Authors: El-Mas Mahmoud M. , Carroll Robert G. , Abdel-Rahman Abdel A.
Published: April 2011

This study evaluated the role of sympathetic nervous system (SNS) activity, peripheral hemodynamic changes, and pressure diuresis in blood pressure (BP) normalization in carotid barodenervated rats. The acute and short-term effects of carotid barodenervation or sham operation on blood pressure, heart rate, cardiac output, stroke volume, total peripheral resistance, and plasma catecholamine levels were determined. Changes in plasma volume, urine output, and water and food intakes were also measured. Surgical denervation of the carotid baroreceptors resulted in rapid rises in blood pressure and heart rate in anesthetized rats. These changes were associated with significant increases in plasma catecholamine levels and total peripheral resistance whereas the cardiac index and stroke volume remained unchanged. After recovery from the anesthesia, the blood pressure of carotid barodenervated rats was still significantly higher than that of sham-operated rats at 3 and 24 h after denervation and returned to sham-operated levels by 48 h. Plasma catecholamine levels and total peripheral resistance were higher in carotid barodenervated than in sham-operated rats on the 2 days following surgery. On the other hand, cardiac index (32 ± 1 vs. 40 ± 2 mL∙min−1∙100 g−1 body mass) and stroke volume (205 ± 13 vs. 283 ± 4 μL/beat) were significantly lower on day 2 in carotid barodenervated than in sham-operated rats, which suggests a compensatory role for carotid output in blood pressure normalization after carotid barodenervaton. Both carotid barodenervation and sham operation caused a reduction in water and food intakes but the responses were greater in carotid barodenervated rats. Urine output was drastically reduced for at least 3 days after denervation and so were body masses and water and food intakes. A pressure diuresis that occurred only on the first day after carotid barodenervation when the blood pressure was still elevated may have contributed to blood pressure normalization. Plasma volumes measured 1 and 5 days after carotid barodenervation or sham operation were similar. These findings suggest that blood pressure normalization in carotid-barodenervated rats cannot be accounted for by restoration of the sympathetic nervous system activity to normal levels but rather to a transient pressure diuresis and a reduction in cardiac output which act to offset increases in sympathetic nervous system activity and total peripheral resistance.Key words: carotid barodenervation, blood pressure, sympathetic nervous system, cardiac output, total peripheral resistance, pressure diuresis.
Reduced noradrenaline responsiveness of brown adipocytes isolated from estradiol-treated rats
Authors: Puerta M. , Abelenda M. , Nava M. P. , Fernandez A.
Published: April 2011

High plasma levels of estradiol are known to reduce the GDP binding of brown adipose tissue. Since GDP binding depends on the level of sympathetic discharge to brown adipose tissue, we measured the responsiveness to noradrenaline of brown adipocytes isolated from female rats with high plasma levels of estradiol. Noradrenaline responsiveness was assessed by measuring the respiration rate of isolated brown adipocytes in the presence of different concentrations of noradrenaline. Both control and treated adipocytes showed the same basal respiratory rate (27 ± 6 and 24 ± 4 nmol O2∙min−1∙10−6 cells, respectively). The presence of noradrenaline (0.1, 1, and 10 μM) in the medium increased the respiration rate of both kinds of adipocytes in a dose-dependent manner. However, the response was markedly reduced in adipocytes isolated from estradiol-treated rats. These results suggest that estradiol impairs the responsiveness of brown adipose tissue to the sympathetic nervous system. Three possible mechanisms are suggested as accounting for the observed decreased responsiveness to noradrenaline, i.e., a direct action of estradiol in brown adipocytes, a modulatory role of estradiol in the central control of the sympathetic discharge to brown adipose tissue, and the interference of catechoiestrogens with noradrenaline synthesis at the sympathetic terminals.Key words: brown adipocytes, estradiol, noradrenaline, oxygen consumption, sympathetic nervous system.
Islet transplantation improves glucose oxidation and mechanical function in diabetic rat hearts
Authors: Lopaschuk G. D. , Lakey J. R. T. , Barr R. , Wambolt R. , Thomson A. B. R. , Clandinin M. T. , Rajotte R. V.
Published: April 2011

In poorly controlled diabetes an impairment of glucose use can contribute to a depression in mechanical function of rat hearts. In this study we determined the effects of islet transplantation on glucose use and heart function in streptozotocin-induced diabetic rats. Myocardial function, glycolysis, and glucose oxidation were measured in isolated working hearts obtained from control, diabetic, and islet-transplanted diabetic Wistar–Furth rats. Islets (1200) were transplanted beneath the kidney capsule 2 weeks after a single i.v. dose of streptozotocin (55 mg/kg). The study consisted of three groups: (i) islet-transplanted diabetic rats, (ii) untreated diabetic controls, and (iii) normal controls. Following 11 weeks of monitoring, working hearts were perfused at a 11.5-mmHg (1 mmHg = 133.3 Pa) preload and 80-mmHg afterload, with buffer containing 11 mM [5-3H, 14C(U)]glucose, 1.2 mM palmitate, and 100 μU/mL insulin. In untreated diabetic rat hearts, glucose oxidation rates were markedly depressed compared with control hearts (30.4 ± 4 and 510 ± 68 nmol∙g−1 dry wt.∙min−1, respectively). Low glucose oxidation rates in diabetic rats were significantly improved in islet-transplanted animals (234 ± 39 nmol∙g−1 dry wt.∙min−1). The low glucose oxidation rates in untreated diabetic rat hearts were accompanied by an impaired mechanical function compared with control hearts, which was improved by islet transplantation (heart rate × developed pressure × 10−3 was 10.6 ± 0.9, 14.8 ± 1.3, and 14.8 ± 1.5 beats∙mmHg∙min−1, respectively). In the presence of insulin, steady-state rates of glycolysis were only slightly depressed in untreated diabetic rat hearts compared with control (1944 ± 436 and 2720 ± 265 nmol∙g−1 dry wt.∙min−1, respectively). However, during a reduction of coronary flow to 0.5 mL∙min−1, glycolytic rates accelerated in control and islet-transplanted rat hearts, but not in untreated diabetic rat hearts. These data show that the decrease in glucose use that occurs in untreated diabetic rats under both aerobic and ischemic conditions can be significantly alleviated by islet transplantation. The increase in glucose oxidation in aerobic hearts supports our previous studies, which suggest that increasing glucose oxidation can improve function in diabetic rat hearts.Key words: glucose oxidation, glycolysis, diabetes, islet transplantation.
Correlates and determinants of bone mineral content and density in healthy adolescent girls
Authors: Rice S. , Blimkie C. J. R. , Webber C. E. , Levy D. , Martin J. , Parker D. , Gordon C. L.
Published: April 2011

The relationships between whole-body and lumbar spine bone mineral content and density, and measures of chronologic age, body composition, physical activity, cardiorespiratory and strength fitness, gynecologic attributes, sexual maturity, and endocrine status were studied in 35 healthy menarcheal girls (14–18 years of age). Body mass (0.464 < r < 0.704), growth hormone (−0.34 < r < −0.42), and one-repetition maximum double-leg press strength (0.343 < r < 0.467) were significantly (p < 0.05) correlated with each of the five bone mineral measures. Multiple regression analysis indicated that body mass accounted for the largest significant proportion of the explained variance (30.2–68.2%) in each of the five bone mineral measures. Age at first menses accounted for a smaller but still significant proportion of the variance in whole-body bone mineral content (4.05%) and lumbar spine bone mineral content (8.06%). Growth hormone entered the regression model as an important predictor of whole-body bone mineral content, accounting for 3.51% of the explained variance in this variable. Age, cardiorespiratory fitness, level of habitual activity, and strength did not contribute significantly to the explained variance in any of the bone mineral measures. Body mass appears to be the single most important determinant of bone mineral among females during this developmental period.Key words: bone density, adolescent girls, body composition, physical fitness, gynecologic characteristics, endocrine factors.
Release of fatty acid binding protein and lactate dehydrogenase from isolated rat heart during normoxia, low-flow ischemia, and reperfusion
Authors: Vork Michaël M. , Glatz Jan F. C. , Surtel Don A. M. , Vusse Ger J. Van der
Published: April 2011

The present study was performed to monitor the effect of low-flow ischemia and reperfusion on changes in the protein permeability of the cardiomyocyte cell membrane and the endothelial cell layer for two cytoplasmic proteins, i.e., fatty acid binding protein (FABP) and lactate dehydrogenase (LDH), which differ appreciably with respect to physicochemica¡ characteristics. To accomplish this, isolated rat hearts were Langendorff perfused with separate collection of vascular and interstitial effluents. Control hearts were perfused normoxically for 300 min, whereas experimental hearts were subjected to 60 min normoxia (N), 180 min low-flow ischemia (I), and finally 60 min normoxic reperfusion (R). Protein release was measured in 15 min interval fractions. During the first 240 min of perfusion 0.2% of total tissue FABP and 1.1% of total tissue LDH were detected in the effluents in both groups. Moreover, in each case 80% of released FABP and LDH was found in the interstitial effluent. During R, following I in the experimental group, appreciable amounts of both proteins were released (2.2 and 5.1% of total tissue contents for FABP and LDH, respectively). During this period the percentage of protein released in the vascular effluent increased significantly for both proteins. It is concluded that the combination of low-flow ischemia and reperfusion increases the protein permeability of both the cardiomyocyte cell membrane and the endothelial barrier. Since the release patterns of FABP and LDH with respect to time were similar during the entire perfusion protocol, it is tempting to state that protein release from tissue is a nonspecific effect of a noxious intervention. However, because the release of LDH was 6-fold higher during low-flow ischemia and 2- to 3-fold higher during reperfusion than that of FABP, it is most likely that protein release from tissue depends on a number of physicochemical properties of both the protein and the (intra)cellular environment.Key words: isolated rat heart, Langendorff perfusion, low-flow ischemia, reperfusion, protein release.
Early incidence of adriamycin treatment on cardiac parameters in the rat
Authors: Cottin Yves , Ribugt Christophe , Maupoil Véronique , Godin Diane , Arnould Laurent , Brunotte François , Rochette Luc
Published: April 2011

To evaluate the early effect of low doses of adriamycin (ADR) on cardiac parameters, male Wistar rats were injected with ADR (1 mg∙kg−1∙day−1) or saline for 10 days. Seven days later, T1 and T2 relaxation times were determined in left ventricular (LV) free wall, septum, and thigh muscle samples. In another experiment, performed on isolated working hearts of rats pretreated with ADR, LV performance was determined along with an index of myocardial lipid peroxidation in this tissue. Lipid peroxidation was enhanced (p < 0.05). This change was not associated with a reduced LV performance, since both aortic and cardiac flows measured in working heart preparations were similar between control and treated rats. However, the coronary flow was significantly reduced (control group, 21 ± 1 mL∙min−1∙g−1, ADR group, 15 ± 1 mL∙min−1∙g−1; p < 0.001). T1 increased in the LV free wall (665 ± 3 to 696 ± 5 ms, p < 0.001) and in the septum (657 ± 3 to 696 ± 5 ms, p < 0.01), while T2 increased only in the LV free wall (50.8 ± 0.9 to 53.1 ± 0.6 ms, p < 0.05). Myocardial water content was also significantly increased. No modification was observed in the thigh muscle samples. Thus, modifications of T1 and T2 relaxation times following ADR treatment are associated with biochemical changes implicating lipid peroxidation. These changes in relaxation times appeared earlier than hemodynamic deterioration and could provide a basis for the application of proton nuclear magnetic resonance imaging in the early detection of cardiac ADR toxicity.Key words: adriamycin cardiotoxicity, malondialdehyde, proton nuclear magnetic resonance, rats, working heart.
Atrial natriuretic peptide release from the ventricles in response to exercise in dogs with atrioventricular block
Authors: Béliveau Louise , Péronnet François , Bichet Daniel G. , Nadeau Réginald
Published: April 2011

The purpose of this study was to examine atrial natriuretic peptide (ANP) secretion at rest and in response to moderate treadmill exercise (10 min, 4 km/h, 26% slope) in control dogs (n = 17) and in dogs (n = 14) with complete atrioventricular block produced by electrocauterization of the His bundle. Atrial rates were similar in both groups (103 ± 13 vs. 102 ± 9 beats/min at rest and 162 ± 10 vs. 160 ± 17 beats/min at exercise in control dogs and in dogs with atrioventricular block, respectively; mean ± SE), but ventricular rate was markedly lower in dogs with atrioventricular block (47 ± 9 and 61 ± 10 beats/min at rest and exercise, respectively). The lower ventricular rate was associated with an increased cardiac preload, as evidenced by the higher right atrial pressure in dogs with atrioventricular block at rest (2.2 ± 1.4 vs. 1.1 ± 0.9 mmHg; p < 0.05) and exercise (7.6 ± 3.1 vs. 4.2 ± 1.7 mmHg; p < 0.05). Arterial plasma ANP concentrations were markedly higher at rest (151 ± 21 vs. 36 ± 10 pg/mL; p < 0.05) and exercise (353 ± 31 vs. 72 ± 17 pg/mL; p < 0.05) in dogs with atrioventricular block. This observation supports the hypothesis that atrial wall stretching is a major stimulus for ANP release at rest and exercise. Ventricular release of ANP could also contribute to the higher plasma ANP concentrations observed both at rest and during exercise in dogs with complete atrioventricular block. Indeed, a large ANP concentration gradient was measured between the aorta and the distal part of the coronary sinus in these dogs at rest (227 ± 55 pg/mL) and exercise (240 ± 57 pg/mL) but not in control dogs. Changes in heart rate and in vasopressin and catecholamine concentrations do not appear to play a major role in the control of ANP release. Finally, the higher arterial ANP concentrations in dogs with complete atrioventricular block do not modify the activity of the renin–angiotensin–aldosterone system at rest, nor its response to exercise.Key words: catecholamines, aldosterone, vasopressin, natriuretic peptide.
Reduced responses of retinal vessels of the newborn pig to prostaglandins but not to thromboxane
Authors: Abran Daniel , Varma Daya R. , Li Ding-You , Chemtob Sylvain
Published: April 2011

The upper blood pressure limit of retinal blood flow autoregulation is lower in the newborn than in the adult; this suggests an insufficient vasoconstrictor response in the newborn when perfusion pressure is increased. Because prostaglandins (PGs) have an important role in autoregulation of retinal blood flow, we compared the effects of PGE2, PGF2α, carbacyclin (PGI2 analogue), and U46619 (thromboxane analogue), as well as that of agonists for the three different PGE2 receptor subtypes, 17-phenyl trinor PGE2 (EP1), butaprost (EP2), and M&B 28,767 (EP3), on the retinal vasculature of newborn and adult pigs, using isolated eyecup preparations. PGF2α and PGE2 caused a markedly greater constriction of retinal arteries and veins of the adult than of the newborn animals. Further analysis of the response to PGE2, using receptor subtype agonists, revealed that the EP1 receptor agonist, 17-phenyl trinor PGE2, and the EP3 receptor agonist, M&B 28,767, caused a significant constriction of adult arteries and veins but produced minimal effects on newborn vessels; the EP2 receptor agonist, butaprost, caused a small and comparable dilation of newborn and adult arteries and veins. The PGI2 analogue, carbacyclin, caused a greater dilation of the adult than of the newborn arteries, but produced comparable dilation of veins from both newborn and adult animals. In contrast to the effects of PGF2α and PGE2, the thromboxane analogue, U46619, as well as the α1-adrenoceptor agonist, phenylephrine, significantly constricted newborn arteries and veins, and this effect was comparable with that observed on retinal vessels of the adult. Our findings indicate that the retinal vasculature of the newborn responds minimally to prostaglandins, primarily PGF2α and PGE2, compared with the adult, but constricts effectively to thromboxane. Since prostaglandins play an important role in the autoregulation of retinal blood flow, our observations provide an explanation for the inability of the newborn to limit blood flow when perfusion pressure is raised.Key words: retinal vascular responses, prostaglandins, thromboxane, PGE2 receptor subtypes.
Effects of dietary zinc deficiency on the hepatic microsomal cytochrome P450 2B in rats
Authors: Xu Zhaoming , Squires E. James , Bray Tammy M.
Published: April 2011

This study was conducted to investigate whether the effects of zinc deficiency on the in vitro and in vivo drug metabolism in rats results from an altered expression of hepatic microsomal P450, particularly P450 2B (2B), in rats. Three-week-old, male Wistar rats were randomly assigned to three groups: a zinc-adequate ad libitum (ZnAL), zinc-adequate pair-fed (ZnPF), and zinc-deficient (ZnDF) group. After 3 weeks on the diet, each dietary group was further divided into drug control and phenobarbital (PB, 100 mg/kg, 3 days, ip) group. Within the drug control group, total microsomal P450 concentration was lower in both ZnPF and ZnDF than in ZnAL. Zinc deficiency resulted in a decreased aminopyrine N-demethylase (AD) activity expressed per milligram protein, with no effect on benzphetamine N-demethylase (BD) activity. The constitutive level of 2B protein and mRNA was not affected by dietary treatments. The level of NADPH–P450 reductase in ZnDF was significantly higher than in ZnAL and ZnPF. PB treatment significantly induced total microsomal P450 concentration, AD and BD activities expressed per milligram protein, 2B protein and mRNA levels, and NADPH–P450 reductase level in all dietary groups. In summary, the constitutive level of AD activity, but not BD activity, was decreased in dietary zinc deficient rats. The constitutive levels of 2B protein and mRNA were not affected by dietary zinc deficiency. PB-induced expression of 2B, both transcriptionally and translationally, and the induction of AD and BD activity by PB were not affected by zinc deficiency in rats. Severe feed restriction had no effect on the levels of both constitutively and inductively expressed AD and BD activities, 2B protein, and 2B mRNA.Key words: dietary zinc deficiency, 2B protein and mRNA, 2B activity, induction of 2B, phenobarbital.
Cytochrome P4S0 during ontogenic developments occurrence in the ductus arteriosus and other tissues
Authors: Coceani Flavio , Kelsey Lois , Ackerley Cameron , Rabinovitch Marlene , Gelboin Harry
Published: April 2011

Our previous investigations have implicated a cytochrome P450 mechanism in the oxygen contraction of the ductus arteriosus and, by extension, in the closure of the vessel at birth. This study was undertaken in fetal and newborn sheep to characterize the ductal cytochrome and gather insight into its operation. Other tissues, vascular and extravascular, were used as a reference. Benzo[a]pyrene hydroxylation (a marker for the 3-methylcholanthrene-inducible isozyme) and aminopyrine N-demethylation (a marker for the glucocorticoid-inducible isozyme) had insignificant activity in the ductus and aorta from fetal sheep, and no increase was noted after exposing the animal in utero to β-naphthoflavone or dexamethasone, both alone and in combination with phenobarbital. However, dexamethasone and, particularly, dexamethasone plus phenobarbital produced a variable constriction of the fetal ductus. No monooxygenase activity was found in the naturally closing ductus of the newborn. Conversely, both enzyme reactions were measurable in the fetal liver, and they became more active after treatment with the inducers or at birth. Scanning immunoelectron microscopy of cultured endothelial and muscle cells from both ductus and aorta showed specific gold labelling for the glucocorticoid-inducible cytochrome P450 only in ductal muscle. By transmission electron microscopy, this immunoreactivity was located along the sarcolemma and in the sarcoplasmic reticulum. These findings indicate the presence in the ductus arteriosus of a cytochrome P450 belonging to the 3A subfamily. However, considering the uneven action of the inducers on enzyme activity in ductal tissue and muscle tone, the role of this cytochrome in closure of the vessel at birth remains to be ascertained.Key words: ductus arteriosus closure, oxygen, cytochrome P450.
Transient benzodiazepine – GABAA receptor increase after a passive avoidance learning in synaptosomal membranes from chick forebrain
Authors: Martijena I. D. , Arce A.
Published: April 2011

One-day-old chicks were exposed to a one-time passive avoidance learning task. After chicks peck a bead dipped in a bitter-tasting liquid, they learn to stop pecking the bead. Radioligand binding analysis of [3H]flunitrazepam was performed on crude synaptosomal membranes from forebrains, at 10, 30, and 60 min post-training. Water-trained chicks (control) pecked a bead dipped in water, and they did not learn to stop pecking the bead. The water control was complemented with a methyl anthranilate fed control chick to demonstrate that taste per se does not affect the [3H]flunitrazepam binding. At 30 min in relation to 10 min post-training, the Bmax increased 31% in water-trained chicks and 56% in taste-trained chicks, with Bmax of the taste-trained chicks reaching a value 22% higher than that in water-trained chicks. The difference, attributable to the learning, disappeared at 60 min post-training, and at all times the affinity remained unchanged. The Bmax increase in water-trained chicks might be attributable to psychological stress accompanying the task and the Bmax increase in taste-trained chicks attributable to the learning in addition to the stress accompanying the task. The results suggest that the receptor increase associated with learning is involved in early stages of memory formation.Key words: chick learning, stress, chick forebrain, flunitrazepam binding.
Platelets, vascular disease, and diabetes mellitus
Authors: Winocour Peter D.
Published: April 2011

Diabetes is associated with increased risk for atherosclerosis and its thromboembolic complications. Theories about mechanisms of atherosclerosis in diabetes are similar to those in the nondiabetic population. Platelets contribute to atherosclerosis through effects on vessels by materials released from the platelets, which interact with injured or altered vessels. In diabetes, platelets could contribute to enhanced atherosclerosis through hypersensitivity to agonists at sites of vessel injury and increased release of materials from adherent platelets. Diabetic platelets are hypersensitive to agonists in vitro, and alterations in a number of mechanisms involved in platelet activation occur in these platelets, which could contribute to the hypersensitivity. These alterations include increased presence of glycoprotein receptors for agonists and adhesive proteins on the platelet surface, increased fibrinogen binding, decreased membrane fluidity, enhanced arachidonate pathway activation with increased thromboxane A2 formation, and increased phosphoinositide turnover leading to increased inositol trisphosphate production, Ca2+ mobilization, and protein phosphorylation. There is some evidence for increased platelet activity in vivo in diabetes, but it is unclear whether this reflects platelet hypersensitivity or increased platelet turnover on already diseased vessels. Studies in diabetic animals indicate greater interaction of platelets with injured vessels and incorporation into experimentally induced thrombi, but it is unclear if this reflects changes in platelets or other factors. These changes could be contributing to the enhanced atherosclerosis and its clinical complications in diabetic patients.Key words: platelets, vascular disease, diabetes mellitus.
Extrasynaptic effects of GABA (γ-aminobutyric acid) agonists on myelinated axons of peripheral nerve
Authors: Liske S. , Morris M. E.
Published: April 2011

Effects of the inhibitory neurotransmitter, GABA (γ-aminobutyric acid) on the excitability of myelinated fibers of isolated amphibian sciatic nerves and their dorsal and ventral spinal roots have been compared with those of a GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), and the GABAB agonist baclofen. Graded, prolonged increases in the amplitude of A-fiber half-maximal compound action potentials of Rana ballenderi sciatic nerves were evoked by GABA (Rmax = 49%, EC50 = 0.1 mM); responses to THIP were smaller (Rmax = 34%, EC50 = 1.1 mM) and with a different, distinctly biphasic recovery phase. In studies of Rana catesbeiana nerves and their attached spinal roots, excitability increases produced in fibers of the ventral roots by GABA were smaller than those of the dorsal roots. Peak changes evoked by THIP in both roots were similar to the effects of GABA on the ventral root; however, THIP's ventral root response showed much less sensitivity and was followed by a rapid recovery phase, undershoot, and secondary, prolonged enhancement. Bicuculline methiodide antagonized agonist-induced increases, and revealed the presence of significant decreases in excitability of the ventral root fibers at concentrations of GABA or THIP < 3 mM. Baclofen evoked inconsistent changes in the excitability of whole nerve and root fibers; small increases occurred with lower doses and secondary, delayed decreases with higher doses. The high concentration (≥ 0.1 mM) of the active isomer needed to cause a small response suggests a limited contribution and (or) presence of GABAB receptors. GABA and its agonists evoke complex, multiphasic excitability changes in the myelinated axons of the spinal roots and peripheral nerve. Contributions of different phases of increase and directions of change signify the participation of multiple receptors and (or) mechanisms. Responses of the dorsal root appear to reflect mainly GABAA-mediated increases in excitability; those of the ventral root include an additional or greater decrease, which may reflect a hyperpolarizing component mediated by a GABAC-like or bicuculline methiodide insensitive GABAA receptor. The large, prolonged responses of the sensory axons to GABA may be linked to their greater K+ channel conductance and related to the inhibitory transmitter's depolarizing action at the more proximal site of their central presynaptic terminals.Key words: dorsal and ventral roots, amphibian, excitability, GABAA, GABAB, GABAC.
Renal vascular effects of epinephrine infusion in the halothane-anesthetized piglet
Authors: Harrington Keith J. , Allen Robert G. , Dewald Jay W.
Published: April 2011

The objective of this study was to determine the dose–response effects of epinephrine, given by systemic intravenous infusion to the halothane-anesthetized newborn piglet, on renal blood flow, mean arterial blood pressure, and renal vascular resistance. Seven newborn piglets were acutely instrumented. A transit-time ultrasound flow probe was placed around the renal artery and a femoral arterial catheter was placed for blood pressure monitoring. Epinephrine was infused in doubling doses from 0.2 to 3.2 μg∙kg−1∙min−1. Mean arterial blood pressure increased from 54 mmHg (1 mmHg = 133.3 Pa) to an average of 96 mmHg at 3.2 μg∙kg−1∙min−1 of epinephrine. Renal blood flow increased from 165 mL∙min−1∙100 g−1 at baseline to 185 mL∙min−1∙100 g−1 at a dose of 0.2 μg∙kg−1∙min−1 and increased further at 0.4 and 0.8 μg∙kg−1∙min−1 to reach 261 mL∙min−1∙100 g−1. Renal blood flow began to fall at a dose of 3.2 μg∙kg−1∙min−1, remaining however, significantly above baseline (211 mL∙min−1∙100 g−1). Consequently, calculated renal vascular resistance fell as the dose was increased from 0.2 to 0.8 μg∙kg−1∙min−1 and then rose again at 1.6 and 3.2 μg∙kg−1∙min−1, being significantly above baseline at 3.2 μg∙kg−1∙min−1. These results demonstrate that epinephrine when given by systemic infusion to the halothane-anesthetized newborn pig is a renal vasodilator at low doses and causes renal vasoconstriction at moderate to high doses. Renal blood flow remained above baseline at all doses tested, and thus, within the dosage range tested, epinephrine infusion should not cause renal ischemia.Key words: epinephrine, kidney blood flow, piglet, renal vascular resistance.
Selectlve desensitization of 5-hydroxytryptamine 2A receptor mediated contraction in guinea pig trachea
Authors: Watts Stephanie W. , Schenck Kathryn W. , Cohen Marlene L.
Published: April 2011

5-Hydroxytryptamine (serotonin, 5-HT) contracts the guinea pig trachea through stimulation of 5-HT2A receptors, an effect previously reported to rapidly desensitize. The present studies were designed to examine further the putative desensitization to serotonin. In vitro studies investigating functional desensitization of the guinea pig tracheal 5-HT2A receptor documented that 5-HT (3 × 10−7 M) significantly (50%) but incompletely reduced subsequent tracheal maximal contraction to 5-HT. In contrast, an equieffective concentration of carbamylcholine (3 × 10−8 M) did not reduce guinea pig tracheal contraction to 5-HT. Furthermore, 5-HT (3 × 10−7 M) did not diminish tracheal contraction to carbamylcholine. These data indicate that 5-HT can selectively desensitize guinea pig tracheal contraction to 5-HT. In addition, 5-HT-induced contraction but not carbamylcholine-induced contraction in guinea pig trachea declined over time, an effect that was more pronounced at high concentrations of 5-HT (1 × 10−6 and 1 × 10−5 M). Inhibitors of mechanisms that oppose contractility to 5-HT (5-HT-induced relaxation, uptake of 5-HT, or metabolism of 5-HT) did not reverse the decline in contraction to 5-HT (1 × 10−5 M). The decline in 5-HT-induced contraction was most rapid in the guinea pig trachea and less so in the rat jugular vein and rat aorta, two preparations in which 5-HT induced contraction also occurred via activation of 5-HT2A receptors. These studies suggest that 5-HT can functionally and selectively desensitize the 5-HT2A receptor in guinea pig trachea, an effect not likely to be related to opposing actions of 5-HT or reduction in concentration of 5-HT.Key words: phosphatidylinositol hydrolysis, receptor desensitization, smooth muscle.
Glucose transporters (GLUTs 1–4) and their mRNAs in regions of the rat brain: insulin-sensitive transporter expression in the cerebellum
Authors: Rayner D. V. , Thomas Moira E. A. , Trayhurn Paul
Published: April 2011

Major regions of the rat brain have been examined for the presence of glucose transporters (GLUTs 1–4) and their mRNAs. Both the mRNA and immunoreactive protein for GLUT1 and GLUT3 were found in each brain region (medulla, pons, cerebellum, midbrain, hypothalamus, thalamus, hippocampus, parietal cortex). The mRNA and protein for GLUT4 were identified in the cerebellum, but not elsewhere in the brain. GLUT2 protein and mRNA were not detected in any region of the brain. Although GLUT1 and GLUT3 are the major brain glucose transporters, the presence of GLUT4 in the cerebellum suggests that insulin-sensitive glucose uptake may occur in a specific part of the brain.Key words: glucose transporters, GLUT4, brain, cerebellum, digoxigenin-labelled oligonucleotide.
Central Neural Mechanisms of Prehension
Authors: Lawrence Donald G.
Published: April 2011

The digital dexterity seen in man and macaque monkeys but not present in other primates, such as the squirrel monkey, occurs without anatomical specialization of the hand. The central nervous system apparatus essential to such dexterity resides in the motor cortex and its outflow to lower centres. Areas other than the motor cortex are involved in the initiation and execution of complex sequential movements, including those of the fingers and hand. These include the supplementary motor and premotor areas of the cerebral cortex and the lateral parts of the cortex and the deep nuclei of the cerebellum.Key words: motor cortex, corticomotoneuronal projections, supplementary motor area, premotor area, cerebellum.
Doxorubicin-induced changes in intracellular Ca2+ transients observed in cardiac myocytes isolated from guinea-pig heart
Authors: Jiang Jiahua , Temma Kyosuke , Akera Tai
Published: April 2011

Effects of doxorubicin on intracellular Ca2+ concentrations ([Ca2+]i) were examined using myocytes isolated from guinea-pig heart and loaded with fura 2. Changes in twitch contractions were assessed from the motion of myocytes. Ca2+ transients and contractions were triggered by electrical-field stimulation. Exposure of myocytes to doxorubicin depressed Ca2+ transients and contractions. The time to peak Ca2+ transient was prolonged, and Ca2+ sequestration was delayed. In myocytes treated with doxorubicin, an increase in external CaCl2 concentration from 1.2 to 3.6 mM increased the resting and peak [Ca2+]i and enhanced twitch contraction. In the presence of 3.6 mM CaCl2, isoproterenol failed to enhance Ca2+ transients or contractions of doxorubicin-treated myocytes. Effects of doxorubicin were compared with those of agents known to alter Ca2+ handling by myocytes. Caffeine enhanced the peak and resting [Ca2+]2 and contraction. Verapamil caused a rapid decrease in Ca2+ transients and twitch contractions. The effects of verapamil were reversed by isoproterenol in the presence of 3.6 mM CaCl2. Ryanodine alone and combined with doxorubicin depressed contractions and Ca2+ transients and elevated resting [Ca2+]i. Resting [Ca2+]i was further elevated by an increase in CaCl2 concentration and the addition of isoproterenol. The combination of verapamil and ryanodine inhibited Ca2+ transients and contractions. In the presence of verapamil and ryanodine, an increase in extracellular CaCl2 concentration increased resting and peak [Ca2+]i. Isoproterenol further elevated resting and peak [Ca2+]i and increased twitch contractions. These results indicate that doxorubicin alters cellular Ca2+ handling. The actions of doxorubicin are not mimicked by caffeine, verapamil, ryanodine, or the combination of verapamil and ryanodine. Among these agents, ryanodine produced effects that were closest to those observed with doxorubicin.Key words: doxorubicin cardiotoxicity, intracellular calcium, myocytes, ryanodine, verapamil, caffeine, isoproterenol, fura 2, guinea pig.
Oxytocin induces an inward current in pregnant rat myometrial cells
Authors: Shimamura Keiichi , Kusaka Masumi , Sperelakis Nicholas
Published: April 2011

The effects of oxytocin (OT) on holding current were studied in uterine smooth muscle cells freshly isolated from the longitudinal layer of 18–20 day pregnant rats, using the nystatin method of whole-cell voltage clamp. As we previously reported, the voltage-dependent Ca2+ current (L type) was partially inhibited by OT (about 30% inhibition at 1 μM). When the cells were held at the holding potential (HP) of −60 mV and the holding current was monitored, OT induced an inward current. The amplitude of this OT-induced current was 72 ± 26 pA (n = 27). When the cell was held at more positive potentials (HP 0 or +40 mV), the OT-induced current reversed direction, becoming outward. This current usually was long lasting (74% of cells responding to OT); a transient current was observed in 26% of the cells. In the absence of either Na+ or Ca2+ in the bath solution, OT induced an inward current (at HP −60 mV). However, the OT-induced current was absent when both of these ions were omitted from the bath. These results suggest that OT induces an inward current through receptor-activated nonselective cation channels. The resulting increase of intracellular Ca2+ may contribute to the inhibition of voltage-dependent Ca2+ current produced by OT. This OT-induced current may also play an important role for membrane depolarization and accompanying contraction produced by OT in pregnant rat myometrium.Key words: oxytocin receptor activated channel, uterine smooth muscle, pregnant rat myometrium, holding current, whole-cell voltage clamp.
Fructose loading induces cardiovascular and metabolic changes in nondiabetic and diabetic rats
Authors: Dai Soter , Todd Mary E. , Lee Stephanie , McNeill John H.
Published: April 2011

The effects of fructose loading on the integrated cardiovascular function in vivo, glycemic control, glucose tolerance, and plasma lipid levels in nondiabetic and streptozotocin (STZ) diabetic rats were investigated. Endothelial morphology of the thoracic aorta was also assessed with scanning electron microscopy. Fructose-loaded nondiabetic rats exhibited elevated blood pressure and pulse rate, and signs of arterial atherogenesis, such as focal adherence of leukocytes and fibrin to the endothelium. Intraperitoneal glucose tolerance tests revealed a greater increase in plasma insulin in response to glucose challenge in these animals than in the control. Compared with the untreated STZ-diabetic animals, fructose-loaded diabetic rats had significantly greater hyperglycemia, glucose intolerance, and hyperlipidemia and higher, blood pressure, but had a similar degree of hypoinsulinemia, cardiac dysfunction, and cardiac enlargement. They also showed signs of early atherogenesis. The central venous pressure and the susceptibilities of the rats to the induction of ventricular arrhythmias by intravenous infusion of aconitine were not significantly affected by either STZ injection or fructose loading. It is concluded that prolonged intake of an excessive amount of fructose has detrimental effects on the cardiovascular system, glucose metabolism, and plasma lipid levels in both nondiabetic and STZ-diabetic rats.Key words: fructose, diabetes, hypertension, myocardial dysfunction, endothelial morphology.
α1-Adrenoceptor subtypes mediating contraction of the femoral artery in spontaneously hypertensive rats
Authors: Fujimoto Seigo
Published: April 2011

α1-Adrenoceptors (ARs) were divided into α1H and α1L subtypes by their different affinities for bunazosin or prazosin. α1H-ARs were further subdivided into α1A, α1B, and α1C subtypes. Therefore, this study was undertaken to determine which α1-AR subtypes were involved in the activation of femoral artery preparations by α1-AR agonists in spontaneously hypertensive rats (SHR). For comparison, aortic strips were also incorporated in the present study. In the presence of propranolol, deoxycorticosterone, and desipramine, norepinephrine (NE) contracted the vascular strips in a dose-dependent manner. Negative log EC50 values and maximum responses of NE-induced contraction of the SHR femoral artery were unchanged and increased, respectively, compared with those of Sprague–Dawley and Wistar–Kyoto rats (WKY). Contractile responses of the SHR aortae to NE were similar to those of the normotensive tissues. Schild plot data for α1-AR antagonists indicated that α1-AR subtypes mediating contraction of the aorta were homogeneous and had high affinities for bunazosin (pA2 9.4, α1H subtype) and WB 4101 (pA2 9.3) and a low affinity for 5-methylurapidil (pA2 7.7). In the femoral artery, because Schild plots for bunazosin had slopes of less than 1.0, there were α1H and α1L subtypes. Bunazosin, at 10−9 M, which could mask the α1H subtype, yielded a Schild plot for bunazosin with a slope not different from unity and decreased the pA2 value for bunazosin (pA2 9.4 vs. 8.5). Chlorethylclonidine inhibited the response of the aortic and femoral preparations to NE but did not change Schild plot data for 5-methylurapidil. It was suggested that in the rat femoral artery, α1C and α1L subtypes mediated the contractile response to NE. The α1-AR subtype in the aorta was essentially identical with the α1H subtype in the femoral artery. α1-AR subtypes mediating contraction in the SHR blood vessels were identical with those in the WKY tissues.Key words: α1-adrenoceptor subtype, blood vessels, spontaneously hypertensive rat.