bluuebunny/crossref_metadata_2025 huggingface dataset:
Seed abundance versus substrate limitation of seedling recruitment in northern temperate forests of British Columbia
Authors: LePage Philip T , Canham Charles D , Coates K Dave , Bartemucci Paula
Published: April 2011

We examine the influence of (i) the spatial distribution and abundance of parent trees (as seed sources) and (ii) the abundance and favourability of seedbed substrates, on seedling recruitment for the major tree species in northwestern interior cedar-hemlock forests of British Columbia, under four levels of canopy openness (full canopy, partial canopy, large gap, and clearcut). Substrate distribution varied with canopy openness, and substrate favourability was a function of both canopy openness and seedling species. Lack of suitable substrates was the predominant factor limiting seedling density under full canopies. Partial canopy and gap sites provided a broad range of favourable substrates in close proximity to parent trees, resulting in the highest observed seedling densities. There was much higher effective dispersion of seedlings away from parent trees in gaps than in the partially cut stands. Seedling dispersion to clearcut sites was poor with seedlings being tightly restricted to a narrow band along the forest edge. Thus, seedling recruitment in these forests was a reflection of the interaction between the abundance of seed and substrate favourability, and the relative importance of these factors varied significantly with canopy structure.
Physical properties of water in relation to stemflow leachate dynamics: implications for nutrient cycling
Authors: Levia Jr. Delphis F , Herwitz Stanley R
Published: April 2011

Stemflow leachate chemistry from a deciduous canopy tree species monitored during late winter and early spring precipitation events demonstrated significant chemical enrichment. By considering stemflow volume and chemical concentration in relation to the quantity that would be expected in a rain gage occupying an area equivalent to the trunk basal area, manganese was found to be enriched by a mean factor of 1450 and potassium by a mean factor of 580. The most pronounced enrichment was documented during a late winter rain-on-snow event characterized by temperature oscillations near the freezing point. During this event, manganese was enriched by a factor of 4400 and potassium by 1715. We conclude that mixed precipitation events with multiple freeze-melt cycles can generate significantly more leachate than spring rainfall events because of lower air temperatures and increased kinematic viscosity and surface tension of stemflow drainage. These physical properties lengthen the residence time of intercepted precipitation on the woody frame of the tree and promote its funneling from inclined branches. Stemflow represents a spatially localized and enriched point input that may affect tree vigor in early spring. The influence of localized aqueous chemical fluxes to the forest floor on forest biogeochemistry and ecophysiological functioning are discussed.
Reconstructing structural development of even-aged larch stands in Siberia
Authors: Osawa Akira , Abaimov Anatoly P , Zyryanova Olga A
Published: April 2011

A method was proposed for quantitatively reconstructing structural development over time of even-aged monospecific forests and was applied to a larch (Larix gmelinii (Rupr.) Rupr.) stand in Siberia. It relies on samples obtained at one-time observation and some simple assumptions considered general in even-aged stands. Tree-ring data taken from breast height of a group of the largest trees and those measured at various stem heights of several individuals representing the range of tree sizes in the plot are used for the estimation. Stand density and parameters of stem volume distribution at a given time in the past were calculated with the "stem slenderness index," and with an assumption of the -3/2 power distribution for the distribution function of stem size, respectively. By developing time-dependent allometric relationships for individual tree attributes, the whole-stand values of stem volume and its increment were reconstructed for several decades of stand development. Estimated history of the changes in stand density, total stem volume, and stem volume growth for the dense larch stand examined, mostly agreed with a separate estimation by the self-thinning assumption.
Effect of nitric oxide synthase inhibition on cardiovascular and hormonal regulation during pregnancy in the rat
Authors: Zhang Yunlong , Kaufman Susan
Published: April 2011

Recent studies have shown that nitric oxide (NO) biosynthesis increases in pregnancy and that inhibition of nitric oxide synthase (NOS) induces some pathological processes characteristic of preeclampsia. The current project sought to study the effect of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10 µg·min-1, sc for 7 days) on plasma volume, plasma atrial natriuretic factor (ANF), plasma endothelin-1 (ET), and plasma renin activity (PRA) during gestation in conscious rats. NOS inhibition caused mean arterial pressure to increase in both virgin and 21-day pregnant rats. Plasma volume fell in the pregnant rats [L-NAME, 4.5 ± 0.3 mL·100 g-1 body wt. (n = 7) vs. D-NAME, 6.8 ± 0.2 mL·100 g-1 body wt. (n = 10); P < 0.05] but not in the virgin rats [L-NAME, 4.3 ± 0.1 mL·100 g-1 body wt. (n = 6) vs. D-NAME, 4.8 ± 0.2 mL·100 g-1 body wt. (n = 8)]. There was no effect of NOS inhibition on plasma ANF levels or PRA in either the virgin or pregnant rats. However, L-NAME did decrease plasma ET levels in the pregnant rats [L-NAME, 19.6 ± 1.6 pg·mL-1 (n = 8) vs. D-NAME, 11.6 ± 2.5 pg·mL-1 (n = 9); P < 0.05]. Our results confirm that NO is involved in cardiovascular homeostasis in pregnancy; NOS inhibition selectively reduces plasma volume in pregnant rats, thus mimicking a major pathophysiological perturbation of preeclampsia. However, it does not induce the hormonal changes characteristic of preeclampsia, namely the decrease in PRA and increase in plasma ET and ANF levels.

Key words: plasma volume, preeclampsia, endothelin, atrial natriuretic factor, plasma renin activity.
Tetracaine stimulates insulin secretion through the mobilization of Ca2+from thapsigargin- and IP3-insensitive Ca2+reservoir in pancreatic β-cells
Authors: Bosqueiro José Roberto , Carneiro Everardo Magalhães , Bordin Silvana , Boschero Antonio Carlos
Published: April 2011

The effect of tetracaine on45Ca efflux, cytoplasmic Ca2+concentration [Ca2+]i, and insulin secretion in isolated pancreatic islets and β-cells was studied. In the absence of external Ca2+, tetracaine (0.1-2.0 mM) increased the45Ca efflux from isolated islets in a dose-dependant manner. Tetracaine did not affect the increase in45Ca efflux caused by 50 mM K+or by the association of carbachol (0.2 mM) and 50 mM K+. Tetracaine permanently increased the [Ca2+]iin isolated β-cells in Ca2+-free medium enriched with 2.8 mM glucose and 25 µM D-600 (methoxiverapamil). This effect was also observed in the presence of 10 mM caffeine or 1 µM thapsigargin. In the presence of 16.7 mM glucose, tetracaine transiently increased the insulin secretion from islets perfused in the absence and presence of external Ca2+. These data indicate that tetracaine mobilises Ca2+from a thapsigargin-insensitive store and stimulates insulin secretion in the absence of extracellular Ca2+. The increase in45Ca efflux caused by high concentrations of K+and by carbachol indicates that tetracaine did not interfere with a cation or inositol triphosphate sensitive Ca2+pool in β-cells.
Vascular β-adrenoceptor function in hypertension and in ageing
Authors: Werstiuk Eva S , Lee Robert MKW
Published: April 2011

Functional β-adrenoceptors (β-AR) have been identified and characterized in blood vessels under in vivo conditions as well as in vascular smooth muscle cells (SMC) grown in culture. Agonist occupancy of β-AR activates adenylyl cyclase (AC) via the stimulatory guanine nucleotide-binding protein (Gs) and leads to elevations in intracellular adenosine 3',5'-cyclic monophosphate levels (cAMP). Increased cAMP activates the cAMP-dependent protein kinase (PKA), with subsequent phosphorylation of various target proteins. This β-AR pathway interacts with several other intracellular signalling pathways via cross-talk, so that activation by β-AR agonists may also modulate other second messengers and protein kinases. SMC β-AR play an important role in SMC function. In intact blood vessels they mediate SMC relaxation by various intracellular mechanisms, ultimately causing a decrease in intracellular Ca2+levels. In cultured SMC, activation of the β-AR pathway results in inhibition of cellular proliferation, the development of SMC polyploidy, and SMC apoptosis. Blood vessels from hypertensive animals are characterized by an increase in SMC cell mass, a greater incidence of SMC polyploidy in the aorta, and an impairment in the β-agonist-mediated SMC relaxation. Some of these changes may result from an attenuation of β-AR function due to agonist-induced receptor desensitization caused by the uncoupling of receptors from the Gs-AC system. The phosphorylated β-AR may in turn trigger new signals and activate different intracellular pathways. However, the details of these mechanisms are still unresolved. Since functional β-AR play such a prominent and multi-faceted role in SMC function, it is important to understand how these diverse physiological effects are mediated by this receptor system, and how they contribute to the development of hypertension. With ageing, a decrease in β-AR-Gs-AC coupling is observed, and this is implicated in the reduced responsiveness of SMC. The similarities in SMC β-AR functional changes in hypertension and in ageing suggest that the underlying mechanisms are also analogous.Key words: smooth muscle, β-adrenoceptors, cyclic AMP, protein kinase A, cell proliferation, polyploidy, relaxation, apoptosis, hypertension, ageing.
Late gestational changes in sympathomimetic sensitivity in primagravid rabbit ligaments
Authors: McDougall Jason J , Bray Robert C , Hart David A
Published: April 2011

The adrenoceptor profile of blood vessels supplying the medial collateral ligament (MCL) of virgin and primagravid (day 29 of pregnancy) rabbit knees was examined. Topical bolus administration of the α1-adrenoceptor agonists methoxamine and phenylephrine, and the α2-adrenoceptor agonist clonidine, to exposed knee joints resulted in a dose-dependent vasoconstriction of ligamentous vessels. The rank order of potency for the α-agonists was found to be phenylephrine > methoxamine > clonidine. Dobutamine, which acts on β1-adrenoceptors, and ritodrine, which is a β2-agonist, imparted a mild vasodilatatory effect on MCL blood vessels with the efficacy of ritodrine being greater than that of dobutamine. In primagravid rabbits, the constrictor effects of methoxamine and phenylephrine were significantly attenuated compared with virgin control animals (P < 0.0001), whereas clonidine-mediated vasoconstriction was unaltered in the gravid animal (P = 0.3957). With respect to β-adrenoceptor activity, the dilatational effect of dobutamine was the same as in controls (P = 0.5294), while ritodrine vasoactivity was completely abolished in primagravid knees (P < 0.005). These findings suggest that the adrenergic control of rabbit MCL blood flow is predominantly mediated by postjunctional α1 and β2-adrenoceptors. Pregnancy leads to either downregulation and (or) desensitisation of α1 and β2-adrenoceptors in the ligament which could disrupt normal joint homeostasis.Key words: knee joints, blood flow, pregnancy, adrenoceptors, ligaments.
Skeletal and heart muscle protein turnover during long-term exposure to high environmental temperatures in young rats
Authors: Samuels S E , McAllister T A , Thompson J R
Published: April 2011

A study was undertaken to determine the long-term effects of a hot environment on protein turnover in skeletal and cardiac muscles of young homeothermic animals. Three groups of 36 male 28 day old rats were housed at 35°C (hot group), 25°C (control group), or 25°C but pair-fed to the intake of the hot group (pair-fed group). Rates of protein synthesis and degradation were measured in vivo on days 5, 10, 15, and 20. By day 20, soleus and gastrocnemius (skeletal muscle) protein masses were 7 and 14% lower in the hot group and 31 and 21% lower in the pair-fed group compared with the control group (P < 0.05). The fractional rate of protein synthesis (ksyn) was on average 11% lower (P < 0.05) in the hot group compared with control rats and was not different from pair-fed rats. The fractional rate of skeletal muscle protein degradation (kdeg) in hot rats was slightly lower than in control rats; kdegwas on average 18% higher (P < 0.05) in the pair-fed group compared with the hot group and this difference appeared to be most prominent on day 5. In heart, by day 20, protein mass was 30% lower in the hot group and 40% lower in the pair-fed group compared with control rats (P < 0.05). ksynwas on average 19% lower (P < 0.05) in the hot group compared with the control group, but not different from pair-fed rats. In the heart there were no differences in kdegamong treatments. Plasma triiodothyronine (T3) concentration was lower in the hot group, but not in the pair-fed group, compared with controls. In conclusion, chronic exposure to hot environments was associated with lower skeletal and cardiac muscle mass and protein turnover; lower protein mass in this tissue was due to decreased ksyn; this is consistent with lower plasma T3concentrations. In pair-fed rats, ksynwas also reduced, but interestingly kdegwas not, resulting in a greater loss of skeletal muscle mass. These results suggest that heat exposure invokes physiological adaptations to preserve skeletal muscle mass despite decreased food intake. In the heart, loss of protein was a result of decreased ksyn, which can be primarily ascribed to lower food intake.Key words: protein synthesis, protein metabolism, acclimation, heat stress.
Effect of maternal nutrient restriction in early to mid gestation and thyrotrophin-releasing hormone on lamb survival following Caesarean section delivery near to term
Authors: Heasman L , Clarke L , Stephenson T , Symonds M E
Published: April 2011

We investigated the influence of restricted maternal nutrition between 28 and 77 days gestation on survival and thermoregulatory adaptation following Caesarean section delivery near to term. This study was designed to examine the hypothesis that adaptation after birth would be compromised in those lambs born to nutrient restricted ewes. We further hypothesised that this would be due in part to inadequate hypothalamic-pituitary-thyroidal function. Lambs born to nutrient restricted ewes were untreated (RU) or treated with thyrotrophin-releasing hormone (TRH; RT) immediately prior to umbilical cord clamping. Single bearing ewes consumed either 6.60 MJ·day-1(controls, n = 4) or 3.00 MJ·day-1(nutrient restricted, n = 15) from 28-77 days gestation, after which all ewes consumed 7.20 MJ·day-1. All lambs born to control ewes commenced continuous breathing and began to shiver following Caesarean section delivery and survived to 6 h after birth. Only 4 out of 9 RU lambs established continuous breathing and survived to 6 h after birth compared with all RT lambs. Six hours after birth, RT lambs possessed perirenal brown adipose tissue with a higher thermogenic activity than 6 h old RU or control lambs. Lamb birth weight was similar in all groups. In conclusion, near-term lambs born to ewes nutrient restricted in early to mid gestation are at increased risk of death following Caesarean section delivery. Survival after birth can be significantly enhanced if TRH is administered to the lambs immediately before delivery.Key words: nutrition, placental weight, sheep.
Copper deficiency and cardiovascular disease: role of peroxidation, glycation, and nitration
Authors: Saari Jack T
Published: April 2011

Dietary copper deficiency causes a variety of cardiovascular deficits. Systemic effects include high blood pressure, enhancement of inflammation, anemia, reduced blood clotting, and possibly arteriosclerosis. Effects on specific organs or tissues include weakened structural integrity of the heart and blood vessels, impairment of energy use by the heart, reduced ability of the heart to contract, altered ability of blood vessels to control their diameter and grow, and altered structure and function of circulating blood cells. In some instances, the cause of a defect can be directly attributed to reduced activity of a specific copper-dependent enzyme. However, three nonspecific mechanisms of damage have been implicated in cardiovascular defects of copper deficiency. They are peroxidation, the interaction of oxygen-derived free radicals with lipids and proteins (possibly DNA); glycation, the nonenzymatic glycosylation of proteins; and nitration, the interaction of nitric oxide and its metabolites with peptides and proteins. Though independently these mechanisms present great potential for damage, the possibility that they may interact presents an added reason for concern. Furthermore, the fact that at least two of these mechanisms are associated with diabetes and aging suggests that copper deficiency may exacerbate deficits associated with these two conditions.Key words: copper, heart, circulation, peroxidation, glycation, nitric oxide.
On your mark, get set: Brainstem circuitry underlying saccadic initiation
Authors: Munoz D P , Dorris M C , Paré M , Everling S
Published: April 2011

Saccades are rapid eye movements that are used to move the visual axis toward targets of interest in the visual field. The time to initiate a saccade is dependent upon many factors. Here we review some of the recent advances in our understanding of the these processes in primates. Neurons in the superior colliculus and brainstem reticular formation are organised into a network to control saccades. Some neurons are active during visual fixation, while others are active during the preparation and execution of saccades. Several factors can influence the excitability levels of these neurons prior to the appearance of a new saccadic target. These pre-target changes in excitability are correlated to subsequent changes in behavioural performance. Our results show how neuronal signals in the superior colliculus and brainstem reticular formation can be shaped by contextual factors and demonstrate how situational experience can expedite motor behaviour via the advanced preparation of motor programs.Key words: superior colliculus, reticular formation, eye movement, saccade, motor preparation, motor control.
Acquisition and development of monkey tool-use: behavioral and kinematic analyses
Authors: Ishibashi Hidetoshi , Hihara Sayaka , Iriki Atsushi
Published: April 2011

Four Japanese macaques were trained in the use of a T-shaped rake. Use the tool and development of the level of the skill of tool-use took place in three distinct stages. During stage 1, two of the monkeys seemed to use insight for initial solution, while fortuitous experiences led the other two monkeys to the solution. All the monkeys used the tool in a stereotyped manner and could retrieve food only when the tool was placed close to the food. At stage 2 the monkeys became able to manipulate the tool in various ways and became able to retrieve the food regardless of its position. By stage 3 they had developed the level of skill required for efficient retrieval. Further experiments revealed that the monkeys attempted to use unfamiliar objects which were similar to the original tool in shape, but not spherical or ring-shaped objects, to rake in the food.Key words: tool-use, macaque monkey, flexibility, biomechanics.
Sulfur-centered reactive intermediates derived from the oxidation of sulfur compounds of biological interest
Authors: Abedinzadeh Z
Published: April 2011

Sulphur compounds play a central role in the structure and activity of many vital systems. In the living cell, sulfur constitutes an essential part of the defense against oxidative damage and is transformed into a variety of sulfur free radical species. Many studies of the chemistry of sulfur-centered radicals using pulse radiolysis and photolysis techniques to detect and measure the kinetics of these radicals have been published and reviewed. This paper discusses the present state of research on the formation and reactivity of certain sulfur-centered radicals [RS·, RSS·, RS·+, (RSSR)·+] and their implications for biological systems.Key words: sulfur-centered radicals, thiylradicals, sulfur-centered radical cation, cation radicals.
Total Ca2+ handling for E-C coupling in the whole heart: An integrative analysis
Authors: Araki Junichi , Mohri Satoshi , Iribe Gentaro , Shimizu Juichiro , Suga Hiroyuki
Published: April 2011

We assessed total Ca2+ handling (transport, flux) in excitation-contraction (E-C) coupling in a beating left ventricle (LV). We developed a new integrative analysis method that utilizes the internal Ca2+ recirculation fraction (RF), O2 consumption ([Formula: see text]o2) for Ca2+ handling, and O2 cost of Emax (contractility index) of the LV. We obtained the RF from the beat constant of the exponential decay component of the postextrasystolic potentiation, and the O2 cost of Emax from [Formula: see text]o2measured at different Emax. Our equation calculated the unknown total Ca2+ handling, futile Ca2+ cycling, and Ca2+ reactivity of Emax from the RF and Ca2+ handling [Formula: see text]o2. The calculated total Ca2+ handling fell between 30 and 110 µmol/kg, depending on Emax and pathological conditions. Our method also allowed an assessment of futile Ca2+ cycling and Ca2+ reactivity of Emax in a beating LV. These data are not available using conventional methods. Our method can be used to better understand the pathophysiology of total Ca2+ handling in a beating heart.Key words: excitation-contraction coupling, myocardial Ca2+, contractility, cardiac O2 consumption.
Hemodynamic and histomorphometric characteristics of dilated cardiomyopathy of Syrian hamsters (Bio TO-2 strain)
Authors: Goineau Sonia , Pape Danielle , Guillo Pascal , Ramée Marie-Paule , Bellissant Eric
Published: April 2011

The natural history of the disease of the dilated strain Bio TO-2 of cardiomyopathic hamsters (CMH) is not totally characterized. We investigated its hemodynamic and histomorphometric characteristics at 140, 180, 220, 260, and 300 days of age. Forty CMH and 40 controls were investigated (8 at each stage). Mean arterial pressure (MAP, carotid artery catheter) and cardiac output and femoral blood flow (CO, FBF, transit time method) were measured in anesthetized animals. Systemic (SVR) and femoral (FVR) vascular resistances were calculated. Atria, left and right ventricles (LV, RV), lungs, and liver were weighed. LV cavity area, LV and RV wall thicknesses and collagen densities were determined (computer-assisted image analyzer). Pulmonary and hepatic congestion were assessed (arbitrary scales). Compared with controls, MAP, CO and FBF were significantly lower in CMH throughout the study (on average: 22%, 34%, 33%, respectively), FVR was significantly increased (+15%), but SVR was not significantly modified. Concerning histomorphometric characteristics, differences between groups significantly increased with age for most variables: at 300 days, atria (+292%), RV (+13%), lungs (+44%), and liver (+23%) weights, LV cavity area (+130%), LV (+364%) and RV (+181%) collagen densities were significantly increased in CMH vs controls, whereas LV (40%) and RV (23%) wall thicknesses were significantly decreased. At 260 and 300 days, CMH showed significant pulmonary congestion without hepatic alteration. Bio TO-2 CMH progressively develop an alteration of cardiac function leading to decreased MAP and musculo-cutaneous blood flow associated with cardiac remodeling including atria hypertrophy and LV dilation, wall thinning and a rise in collagen density.Key words: cardiomyopathy, heart failure, regional blood flow, remodeling.
Preconditioning in the absence or presence of sustained ischemia modulates myocardial Cx43 protein levels and gap junction distribution
Authors: Daleau Pascal , Boudriau Sophie , Michaud Monia , Jolicoeur Christine , Kingma Jr John G
Published: April 2011

In the heart, brief repeated episodes of ischemia prior to a sustained occlusion (ischemic preconditioning; PC) significantly delay the onset of necrosis and arrhythmogenesis. Ischemia has been reported to influence gap junction organization and connexin43 (Cx43) content, but whether PC affects these structures is not known. We investigated the effect of PC (2 cycles of 5-min ischemia plus 10-min reperfusion) followed by prolonged reperfusion without concomitant regional coronary occlusion on the myocardial Cx43 content and its spatial distribution in rabbit hearts. We also compared the effect of sustained ischemia with or without PC on Cx43 spatial distribution. In experiments with PC only, there was an initial decrease in Cx43 levels within the ischemic zone followed by a progressive increase after 48 h reperfusion. Endtoend immunolabeling of Cx43 was augmented in the ischemic region between 24 and 48 h reperfusion; labeling was not uniquely confined to myocyte abutments, but was also dispersed along the sarcolemma. Cx43 immunolabelling was more intense and diffuse in hearts subjected to PC before sustained coronary occlusion (compared to non-PC). These data indicate that gap junctions are significantly altered during brief episodes of ischemia. Reorganization of the gap junction complex could contribute to PC-mediated reductions in cardiac arrhythmias.Key words: ischemic preconditioning, connexin43, gap junction, reperfusion, heart.
Pathophysiological significance and clinical application of ANP and BNP in patients with heart failure
Authors: Yoshimura Michihiro , Yasue Hirofumi , Ogawa Hisao
Published: April 2011

Plasma levels of ANP and BNP increase in accordance with the severity of the heart failure. In severe cases, the amount of BNP secreted surpasses that of ANP. The main secretion site of BNP is the ventricles, and that of ANP is the atria. However, ANP is also secreted from the ventricles as heart failure advances, and thus the ventricles are important sites for both BNP and ANP. It is well known that myocardial stretch is a key factor in the stimulation of the secretion of ANP and BNP, although neurohumoral factors also play a role in the secretion mechanism. The major physiological effects of ANP and BNP are vasodilation, natriuresis, and inhibition of the renin-angiotensin-aldosterone (RAA) and the sympathetic nervous systems; all of which are supposed to suppress the progression of heart failure. The inhibitory action of ANP and BNP on the RAA system has been considered to be an extra-cardiac effect. We recently reported the activation of an angiotensin-converting enzyme and aldosterone production in failing human hearts. ANP and BNP, however, would inhibit aldosterone production, not only in the adrenal cortex but also in cardiac tissue. ANP, and especially BNP, are useful markers of the heart's status during treatment for heart failure. The infusion of synthetic ANP (hANP) or BNP (Nesiritide®) is effective in the treatment of acute heart failure. In Japan, BNP occupies an important position in the diagnosis of chronic heart failure, as ANP does in the treatment of acute heart failure.Key words: natriuretic peptide, heart failure, myocardial infarction, cardiomyopathy, aldosterone.
Thiocyanate as a probe of the cystic fibrosis transmembrane conductance regulator chloride channel pore
Authors: Linsdell Paul
Published: April 2011

Immediately following exposure to thiocyanate (SCN)-containing solutions, the cystic fibrosis conductance regulator Cl channel exhibits high unitary SCN conductance and anomalous mole fraction behaviour, suggesting the presence of multiple anion binding sites within the channel pore. However, under steady-state conditions SCN conductance is very low. Here I show, using patch clamp recording from CFTR-transfected mammalian cell lines, that under steady-state conditions neither SCN conductance nor SCN permeability show anomalous mole fraction behaviour. Instead, SCN conductance, permeability, and block of Cl permeation can all be reproduced by a rate theory model that assumes only a single intrapore anion binding site. These results suggest that under steady-state conditions the interaction between SCN and the CFTR channel pore can be understood by a simple model whereby SCN ions enter the pore more easily than Cl, and bind within the pore more tightly than Cl. The implications of these findings for investigating and understanding the mechanism of anion permeation are discussed.Key words: chloride channel, permeation, anion binding, multi-ion pore behaviour, rate theory model.
Apparent B-type natriuretic peptide selectivity in the kidney due to differential processing
Authors: Kishimoto Ichiro , Hamra F Kent , Garbers David L
Published: April 2011

Two natriuretic peptides, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), are found principally in the heart. In preliminary experiments with mouse kidney cells or slices, we found mouse BNP1-45 much more potent than ANP1-28 in causing elevations of cGMP (>50-fold). The guanylyl cyclase-A (GC-A) receptor has been suggested to represent the primary means by which both peptides signal. In cultured cells overexpressing GC-A, BNP and ANP were almost equivalent in potency, suggesting that a receptor unique for BNP exists in the kidney. However, in mice lacking the GC-A gene, neither BNP nor ANP significantly elevated cGMP in kidney slices. Phosphoramidon, a neutral endopeptidase inhibitor, shifted the apparent potency of ANP to values equivalent to that of BNP, suggesting these kidney cell/slices rapidly degrade ANP but not BNP. Mass spectroscopic analysis confirmed that ANP is rapidly cleaved at the first cysteine of the disulfide ring, whereas BNP is particularly stable to such cleavage. Other tissues (heart, aorta) failed to significantly degrade ANP or BNP, and therefore the kidney-specific degradation of ANP provides a mechanism for preferential regulation of kidney function by BNP independent of peripheral ANP concentration.Key words: guanylyl cyclase-A, atrial natriuretic peptide, B-type natriuretic peptide, neutral endopeptidase.
Cardiorespiratory effects of prolonged angiotensin II block in resting conscious dogs
Authors: Jennings Donald B
Published: April 2011

Intravenous (iv) infusion of the angiotensin II (ANG II) receptor blocker saralasin in resting conscious dogs during physiological pertubations, such as hypotension and prolonged hypoxia, indicates the presence of an ANG II drive to increase respiration and decrease the arterial partial pressure of CO2 (PaCO2). In contrast, in eupneic resting dogs on a regular chow diet, iv infusion of saralasin for short periods (up to 30 min) provides no evidence of a tonic effect of circulating levels of ANG II on acid-base balance, respiration, metabolism, or circulation. However, ANG II influences physiological processes involving salt, water, and acid-base balances, which are potentially expressed beyond a 30 min time period, and could secondarily affect respiration. Therefore, we tested the hypothesis that blocking ANG II with iv saralasin would affect respiration and circulation over a 4-h period. Contrary to the hypothesis, iv infusion of saralasin in resting conscious eupneic dogs on a regular chow diet over a 4-h period had no effects on plasma strong ions, osmolality, acid-base balance, respiration, metabolism, or circulation when compared with similar control studies in the same animals. Thus, ANG II does not play a tonic modulatory role in respiratory control under "normal" physiological conditions.Key words: acid-base balance, arginine vasopressin, saralasin, strong ions, strong ion difference.
Coexisting independent sodium-sensitive and sodium-insensitive mechanisms of genetic hypertension in spontaneously hypertensive rats (SHR)
Authors: Wells Ibert C , Blotcky Alan J
Published: April 2011

Some essential hypertensive patients and genetic hypertensive rat strains have less than the normal levels of Mg2+ tightly bound to the plasma membranes of their erythrocytes and other cells, i.e., the magnesium binding defect (MgBD). This binding defect appears to cause increased passive permeability of the membrane to Na+ and thereby its increased intracellular concentration, particularly if the Na+-extrusion enzyme systems of the cell are also defective. The Na+-Ca2+ exchange system in the cell membrane exports Na+ and imports Ca2+, increasing the tone of the smooth muscle cell and thus producing hypertension (HTn). This HTn is Na+-sensitive. Evidence supporting this postulate was obtained by determining the intraerythrocyte total concentrations of Na+, Ca2+, K+, and Mg2+ in two strains of spontaneously hypertensive rats (SHR and SS/Jr rats, having the MgBD together with the other requisites of the Na+-sensitive pathway) and their respective controls (WKY and SR/Jr rats, in which this complete pathway is absent). The Na+ and Ca2+ concentrations in the hypertensive rats were increased, and that of K+ was decreased. The concentrations of these cations were very similar in the two hypertensive strains. The level of membrane tightly bound Ca2+ in SHR erythrocyte membranes was significantly higher than those in the other three rat strains, which were not statistically different from each other. These results support previously reported evidence of the existence of a novel HTn-generating mechanism in the SHR rat, in which the intracellular Ca2+ concentration is increased as the result of the enhanced diffusion of this ion into the cell and the accompanying deficiency of the Ca2+ extrusion enzyme systems. This pathway is therefore Na+-insensitive, i.e., Ca2+-sensitive.Key words: essential hypertension, Na+-sensitive hypertension, Na+-insensitive hypertension, Ca2+-sensitive hypertension.
Hepatocyte [3H]-palmitate uptake: effect of albumin surface charge modification
Authors: Burczynski F J , Wang G Q , Elmadhoun B , She Y M , Roberts M S , Standing K G
Published: April 2011

The role of plasma proteins on the cellular uptake of lipophilic substrates has perplexed investigators for many years. We tested the hypothesis that an ionic interaction between the proteinligand complex and hepatocyte surface may be responsible for supplying more ligand to the cell for uptake. The surface-charged groups on albumin were modified to yield proteins having a range of isoelectric points (ALB, ALBs, ALBm, ALBe had values of 4.85.0, 4.54.7, 3.03.5, 8.48.6, respectively). [3H]-Palmitate uptake studies were performed with adult rat hepatocyte suspensions using similar unbound ligand fractions in the presence of the different binding proteins. Mass spectrometry, isoelectric focusing (pI), and heptane : water partitioning were used to determine protein molecular weight, pI, and protein-palmitate equilibrium binding constant, respectively. Hepatocyte [3H]-palmitate clearance in the presence of ALBs and ALBm were significantly lower (p < 0.05) than ALB, whereas [3H]-palmitate clearance in the presence of ALBe was significantly higher (p < 0.05) than ALB. The data were consistent with the notion that ionic interactions between extracellular proteinligand complexes and the hepatocyte surface facilitate the uptake of long-chain fatty acids.Key words: uptake, long-chain fatty acid, hepatic, protein, albumin, surface charge, facilitation, ionic interaction.
Further characterization of β3-adrenoceptors in the guinea pig gastric fundus: stereoselectivity, β-adrenoceptor alkylation, and structure-activity relationship
Authors: Horinouchi Takahiro , Koike Katsuo
Published: April 2011

The stereoselectivity of β3-adrenoceptors, the effect of a β-adrenoceptor alkylating agent, and the structureactivity relationship at β3-adrenoceptors were investigated on the guinea pig gastric fundus. Isomeric activity ratios ((+)/()) for isomers of isoprenaline and noradrenaline were 20.9-fold and 43.7-fold, respectively, and were less than those obtained for activation of β1- and β2-adrenoceptors in the guinea pig atria and trachea, respectively. The concentrationresponse curves to the catecholamines (()-isoprenaline, ()-noradrenaline, and ()-adrenaline), the selective β3-adrenoceptor agonist BRL37344 ((R*,R*)-(±)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxyacetic acid sodium), and the nonconventional partial β3-adrenoceptor agonist (±)-CGP12177A ((±)-[4-[3-[(1,1-dimethylethyl) amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride) were resistant to blockade by (±)-pindobind (10 µM), the β-adrenoceptor alkylating agent. Furthermore, (±)-nadolol, which belongs to the aryloxy propanolamine class and has β1- and β2-adrenoceptor antagonistic characteristics, displays agonistic activity at β3-adrenoceptors. These results indicate that pharmacological characteristics of the β3-adrenoceptors of guinea pig gastric fundus differ from those of β1- and β2-adrenoceptors. ()-Noradrenaline and ()-adrenaline were more potent than dopamine and ()-phenylephrine, respectively. In addition, dobutamine was 22-fold more potent than dopamine. These results suggest that the 4-hydroxyl group at the catechol ring and the β-hydroxyl group and the large moiety on the alkylamine chain characterized efficacy at β3-adrenoceptors.Key words: β3-adrenoceptor, stereoselectivity, β-adrenoceptor alkylating, structureactivity relationship, guinea pig gastric fundus.
An integrative, in situ approach to examining K+ flux in resting skeletal muscle
Authors: Lindinger Michael I , Hawke Thomas J , Vickery Lisa , Bradford Laurie , Lipskie Shonda L
Published: April 2011

The contributions of Na+/K+-ATPase, K+ channels, and the NaK2Cl cotransporter (NKCC) to total and unidirectional K+ flux were determined in mammalian skeletal muscle at rest. Rat hindlimbs were perfused in situ via the femoral artery with a bovine erythrocyte perfusion medium that contained either 86Rb or 42K, or both simultaneously, to determine differences in ability to trace unidirectional K+ flux in the absence and presence of K+-flux inhibitors. In most experiments, the unidirectional flux of K+ into skeletal muscle (JinK) measured using 86Rb was 810% lower than JinK measured using 42K. Ouabain (5 mM) was used to inhibit Na+/K+-ATPase activity, 0.06 mM bumetanide to inhibit NKCC activity, 1 mM tetracaine or 0.5 mM barium to block K+ channels, and 0.05 mM glybenclamide (GLY) to block ATP-sensitive K+ (KATP) channels. In controls, JinK remained unchanged at 0.31 ± 0.03 µmol·g1·min1 during 55 min of perfusion. The ouabain-sensitive Na+/K+-ATPase contributed to 50 ± 2% of basal JinK, K+ channels to 47 ± 2%, and the NKCC to 12 ± 1%. GLY had minimal effect on JinK, and both GLY and barium inhibited unidirectional efflux of K+ (JoutK) from the cell through K+ channels. Combined ouabain and tetracaine reduced JinK by 55 ± 2%, while the combination of ouabain, tetracaine, and bumetanide reduced JinK by 67 ± 2%, suggesting that other K+-flux pathways may be recruited because the combined drug effects on inhibiting JinK were not additive. The main conclusions are that the NKCC accounted for about 12% of JinK, and that KATP channels accounted for nearly all of the JoutK, in resting skeletal muscle in situ.Key words: sodium potassium chloride cotransporter, NKCC, Na+/K+-ATPase, potassium channels, potassium transport, in situ rat hindlimb.
Changes in adiponectin expression in acute myocardial infarction rats and the significance of bisoprolol intervention
Authors: Zhang Song , He Ben , Goldstein Steven , Ge Junbo , Wang Zuyue , Ruiz George
Published: April 2011

The aims of this study were to explore the changes in expression of myocardial adiponectin (APN), changes in serum APN, and the significance of bisoprolol intervention in acute myocardial infarction (AMI) rats. An AMI rat model was established for the purposes of this study and was used for analysis of serum APN as determined by ELISA. Changes in expression of myocardial APN mRNA and APN protein in AMI rats were determined via reverse transcriptase (RT)–PCR and immunohistochemistry. Serum APN concentration and APN protein expression of the myocardium decreased significantly in the AMI groups compared with the sham operation group, with the lowest serum APN and APN protein expression on day 7 after AMI. On days 7 and 10 after AMI, the expression of myocardial APN mRNA in the AMI groups decreased significantly compared with the sham operation group. However, the APN mRNA increased on day 10 compared with that on day 7. Notably, there was an increase in levels of serum APN and myocardial APN expression after bisoprolol intervention. The expression of myocardial APN and serum APN decreased in AMI rats. APN may be an important protective factor against AMI. Bisoprolol can also protect against AMI because it increases APN expression.
Apoptosis-inducing factor contributes to epithelial cell apoptosis induced by enteropathogenic Escherichia coli
Authors: Flynn Andrew N. , Wang Arthur , McKay Derek M. , Buret Andre G.
Published: April 2011

The mechanisms by which enteropathogenic Escherichia coli (EPEC) causes intestinal epithelial cell apoptosis remain unclear. We tested the hypothesis that apoptosis-inducing factor (AIF) is involved in apoptosis induced by EPEC. Infection of intestinal epithelial cells in vitro with EPEC led to the mitochondrial and cytosolic accumulation of AIF. This effect was partially dependent on caspase activity. Knockdown of AIF with siRNA blocked cellular apoptosis in response to EPEC infection, as assessed by poly(ADP-ribose) polymerase cleavage and oligonucleosome formation. Taken together, these data suggest that caspase-dependent mobilization of AIF contributes to EPEC-induced epithelial cell apoptosis.
SIALIC ACID CONTENT OF NORMAL RAT LIVER AND OF DAB-INDUCED HEPATOMATA
Authors: Kalant H. , Mons Wilhelmina , Guttman Marta
Published: April 2011

Total sialic acid content of rat livers and tumors was determined by acid hydrolysis of tissue samples, isolation on Dowex-2 columns, and reaction with thiobarbituric acid. Normal rat liver was found to contain 465 μg of neuraminic acid per g of fresh tissue. In rats bearing hepatomata induced by the feeding of p-dimethylaminoazobenzene, the tumors contained an average of 1162 μg/g, while the surrounding liver contained 587 μg/g. Treatment of tissue sections with purified neuraminidase liberated only 27–28% of the sialic acid from liver tissue, but 49% of that in the hepatomata. Paper chromatographic analysis indicated a difference between normal liver and hepatomata with respect to the types of sialic acid present.
THE EFFECT OF TERTIARY AND QUATERNARY ATROPINE ON CORTICAL ACETYLCHOLINE OUTPUT AND ON THE ELECTROENCEPHALOGRAM IN CATS
Authors: Szerb John C.
Published: April 2011

Application of diisopropylfluorophosphate (DFP) to the cortex of non-anesthetized cats resulted in a low output of acetylcholine (ACh) and the appearance of spikes. Intravenous administration of 1 mg/kg atropine sulphate increased ACh output threefold and caused high voltage electroencephalographic (EEG) patterns. While atropine methylbromide given intravenously was 10–20 times less effective than atropine sulphate in producing high voltage EEG, it was only 2–4 times less active in increasing ACh output. Small quantities (0.2 μg/ml) of atropine locally applied also increased ACh output without producing high voltage EEG, but the spikes previously present disappeared. Acetylcholine applied locally following DFP also abolished the spikes. It is concluded that atropine raises ACh output by a direct action on the area of ACh release, independently of EEG effects, and that the site on which cholinergic blocking agents act to raise ACh output is more accessible from the bloodstream than the site responsible for the EEG effects. The exact mechanism by which atropine increases ACh output could not, however, be established.
GLYCYL-PROLINE IN URINE OF HUMANS WITH BONE DISEASE
Authors: Scriver Charles R.
Published: April 2011

An unknown ninhydrin-reacting substance has been found in the urine of three human subjects with rickets. A sample of the substance separated from urine by elution chromatography was hydrolyzed in acid, and equimolar amounts of glycine and proline were released. The DNP reaction applied to the substance resulted in DNP-glycine and free proline. The isolated unknown substance and glycyl-L-proline cochromatographed and coelectrophoresed in a number of solvent and buffer systems. The substance was therefore identified as glycyl-proline.Glycyl-proline is apparently excreted from plasma into urine; it is poorly absorbed by the kidney and its transport is independent of either the glycine or the L-proline transport mechanisms.Glycyl-proline was not excreted by normal subjects. It was found only in patients with severe active rickets. Glycyl-proline excretion paralleled that of total bound hydroxyproline, both diminishing as the rickets healed. Bone collagen appears to be the likely source for glycyl-proline in these patients.
EFFECTS OF RESERPINE AND ADRENALINE ON ATRIAL FIBRILLATION
Authors: Lavallée M. , Tremblay G. , Beaulnes A.
Published: April 2011

The resistance of isolated rabbit atria to arrhythmic factors such as low potassium medium, acetylcholine, and electrical stimulation was determined before and after contact with reserpine and following administration of large doses of adrenaline. Animals pretreated with reserpine were found more sensitive to arrhythmic factors than untreated controls. Moreover, adrenaline was shown, in most cases, to abolish the induced arrhythmias or to lower the frequency of the atrial firing rate. As already suggested by Burn, this antiarrhythmic property of adrenaline at the atrial level is considered to be the result of an antagonism with acetylcholine, presumably through a lengthening of the duration of the action potential.
THE EFFECT OF ACETYLCHOLINE ON ADRENALINE-INDUCED SUBATRIAL RHYTHMS IN THE SENSITIZED CAT HEART
Authors: MacLeod Don P. , Reynolds A. K.
Published: April 2011

Acetylcholine has been shown to be an effective antiarrhythmic agent against arrhythmias induced by adrenaline in combination with the myocardial sensitizers petroleum ether, halothane, and harman methosulphate. It has also been shown that acetylcholine will reduce or prevent the increase in ventricular automaticity produced by adrenaline in the intact cat and in the isolated papillary muscle of the cat. All of these actions of acetylcholine can be blocked by atropine. Evidence from experiments in which petroleum ether inhalation was begun after an arrhythmia had been induced by adrenaline indicated that petroleum ether was causing an increase in ventricular automaticity. The results appear to support the idea that petroleum ether and possibly other sensitizers interfere with the stabilizing action of endogenous acetylcholine on the ventricle and allow the stimulating action of adrenaline to produce severe prefibrillatory rhythms by an increase in ventricular automaticity.
CAPACITY FOR FATTY ACID OXIDATION BY THE BREAST MUSCLE OF THE STARLING (STURNUS ROSEUS) IN THE PRE- AND POST-MIGRATORY PERIODS
Authors: George J. C. , Vallyathan N. V.
Published: April 2011

Studies on the capacity for fatty acid oxidation by the breast muscle homogenate of the migratory starling Sturnus roseus in the pre- and post-migratory periods were carried out, using sodium butyrate as the substrate. It was observed that the oxygen uptake due to the added butyrate in the manometric system during the premigratory period was considerably lower than that in the post-migratory period. During the premigratory period there was more oxygen uptake due to malate oxidation than in the complete system with added butyrate for fatty acid oxidation. The significance of the diminished capacity for fatty acid oxidation in the premigratory period is discussed.