bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of fasting on glucose and palmitate metabolism of perfused rat heart
Authors: Opie Lionel H. , Evans John R. , Shipp Joseph C.
Published: December 2017

The metabolism of glucose U-C14, 5 mm, and palmitate 1-C14, 0.75 mm (complexed to 0.5% albumin), was studied in isolated perfused hearts taken from three groups of rats: fed ad libitum, fasted overnight, or fasted 4 days. The changes in glucose metabolism associated with fasting were: decreased glucose uptake, decreased C14O2 formation, decreased lactate/pyruvate ratio, and decreased incorporation of glucose carbon into glycogen. In contrast, the uptake of palmitate and incorporation of label into C14O2 and tissue fatty acids were similar in the three groups. When the perfusate contained both glucose and palmitate, glucose oxidation was reduced in both fed and fasted states, but palmitate oxidation was virtually unaltered. It is concluded that the nutritional state of the donor rat markedly affects glucose but not palmitate metabolism of the isolated rat heart, and that palmitate is preferentially oxidized in both fed and fasted states. The possible mechanisms involved are discussed.
Inhibition of tonic cardiac sympathetic activity by stimulation of brain septal region
Authors: Manning John W. , Charbon Gerard A. , Cotten Marion deV.
Published: December 2017

Low-intensity electrical stimulation in the region of the medial or lateral septal nuclei of the brain significantly decreased right ventricular contractile force, heart rate, and systemic blood pressure in each of 46 anesthetized cats. These effects developed within 6 sec after onset of stimulation and persisted for about 5 min after cessation of the 10- to 40-sec periods of stimulation. The depressor responses could be elicited repeatedly and were unaffected by bilateral vagotomy, by large doses of cholinergic blocking drugs, or by the antihistamine, diphenhydramine. The decreases in contractile force and heart rate induced by septal stimulation were abolished by extirpation of the stellate ganglia, by tetraethylammonium (TEA) and by the beta adrenergic blocking drug, dichloroisoproterenol (DCI). The characteristic fall in blood pressure induced by septal stimulation was unaffected by stellate ganglionectomy or by DCI. Both TEA and the alpha adrenergic blocking drug, phenoxybenzamine, decreased blood pressure to levels lower than those produced by septal stimulation, and stimulation of the septal nuclei after TEA or phenoxybenzamine did not reduce pressure further. Unlike TEA, phenoxybenzamine had no influence on the decreases in force and rate induced by septal stimulation. The reductions in force and rate were not secondary to hypotension for they were still obtained when aortic pressure was kept constant. These findings suggest that the reductions in contractile force, heart rate, and blood pressure induced by septal stimulation are the result of a decrease in sympathetic tone to the heart and blood vessels.
Calcium and the contractility of arterial smooth muscle
Authors: Hinke J. A. M. , Wilson M. L. , Burnham S. C.
Published: December 2017

The contraction of an isolated arterial segment (500 µ o.d.) was measured as a reduction in flow through its lumen at a constant perfusing pressure. The stimulating agents used to induce contraction were high K+, norepinephrine, and Pitressin. Contraction due to these agents was first abolished after 15 min of perfusion with zero [Ca++]0, then it was re-established by a series of perfusions containing increasing [Ca++]0. During this procedure, high K+ contraction reappeared at 0.5 mmoles/liter [Ca++]0 and increased in proportion to [Ca++]0. Drug contraction, however, reappeared as a near maximal response between 0.5 and 0.75 mmoles/ liter [Ca++]0 and increased relatively little with larger elevations of [Ca++]0. Simultaneous reduction in [Na+]0 potentiated the re-established K+ contraction but had no effect on the re-established norepinephrine contraction. These differences in the Ca++-contractility relationship for drugs and K+ depolarization suggest Ca++ is utilized differently by the two modes of stimulation to bring about contraction.
Influence of amino acids on rat liver phenylalanine hydroxylase activity
Authors: Freedland R. A. , Krakowski M. C. , Waisman Harry A.
Published: December 2017

The influence of oral and of injected amino acids on rat liver phenylalanine hydroxylase activity has been studied in both short-term and extended experiments. Phenylalanine added to the diet in moderate amounts ordinarily causes an increase in enzyme activity, but when excess phenylalanine was included in the diet, it caused a marked decrease in the enzyme activity in rats fed ad libitum. Tryptophan or tyrosine added to the diet in the absence of added phenylalanine increased the enzyme activity in these rats. Excess tryptophan, but not tyrosine, could counteract the effect of phenylalanine on this enzyme after an 18-hr fast. There were dramatic differences in phenylalanine hydroxylase activity when various amino acids were injected. Injection of tryptophan or glycine decreased the phenylalanine hydroxylase activity in rat liver. Injections of other amino acids, notably phenylalanine and tyrosine, had no effect on the phenylalanine hydroxylase activity 5 hr after injection.
Patterns of dietary and hormonal induction of certain NADP-linked liver enzymes
Authors: Tepperman Helen M. , Tepperman Jay
Published: December 2017

Estrogen and thyroxine induction of hepatic hexosemonophosphate shunt and NADP-linked malic dehydrogenases was studied in rats on chow and on a high-fat, low-carbohydrate diet. A different enzyme pattern resulted from treatment with each of the hormones; i.e., estrogen produced a greater effect on the dehydrogenases of the pentose phosphate pathway while thyroxine showed a greater influence on the malic enzyme. Both enzymes were inducible in animals adapted to a high-fat diet, suggesting that accelerated glucose absorption from the gastrointestinal tract is not an essential feature of the mechanism of hormonal induction. However, in the case of the shunt enzymes, availability of dietary carbohydrate resulted in greater increases in enzyme activity than did induction on a high-fat diet. Refeeding a high-carbohydrate diet after a 48-hr fast resulted in a simultaneous increase in both shunt dehydrogenases and malic enzyme, a fact which disproves the hypothesis that the adaptive increase of the former is secondary to a primary increase in the latter.
Effect of fast and hexose injection on serum insulin concentrations of sheep
Authors: Boda J. M.
Published: December 2017

Immunoreactive serum insulin concentration in 15 wethers fasted 16–24 hr was 126 ± 12 µU/ml. Exogenous glucose produced a tenfold increase in serum insulin within 15 min; concentrations remained high for 1 hr and then declined. Fructose increased both blood glucose and insulin. The maximum response of the latter was delayed, in comparison with that produced by glucose injection, and coincided with a rise of blood glucose derived from fructose conversion. Galactose produced a moderate and immediate rise in insulin associated with elevated blood glucose concentrations. There was a positive relationship between the amount of insulin secreted and the utilization rate of injected glucose. Thus, insulin released by glucose loading in the sheep is both immunologically and biologically active. Prolonged fasting depressed glucose tolerance and the amount of insulin secreted following glucose injection. Certain characteristics of the sheep, such as reduced glucose tolerance and low glucose oxidation, are not due to a relative lack of circulating insulin or to an inability of hyperglycemia to mobilize insulin stores.
Accumulation of vitamin A by small intestine of the rat in vitro
Authors: Skála I. , Hrubá F.
Published: December 2017

The vitamin A accumulation by the small intestine of the rat was investigated, using the method of everted intestinal sacs as modified by the authors. For incubation, modified Krebs-Ringer bicarbonate buffer with vitamin A-acetate stabilized with human albumin was used. Vitamin A accumulates in the intestinal wall and the kinetics of this process are analogous to the Michaelis-Menten kinetics. Accumulation is inhibited by KCN and NaF. The transfer of vitamin A into the serosal contents of sacs was minimal. There were no significant differences in the accumulation of vitamin A in various parts of small intestine. It is concluded that the accumulation of vitamin A has a complex and active character.
Influence of estrogens on electrolyte and water exchanges in the ovariectomized rat
Authors: Nocenti M. R. , Cizek L. J.
Published: December 2017

Daily measurements in rats of food and water intakes, and urine and electrolyte excretion during 7 days feeding and 5 days food deprivation were made on the following groups: normal males, normal and ovariectomized females, ovariectomized receiving 10, 50, and 100 µg diethylstilbestrol (DES) or 5 µg estradiol dipropionate, and ovariectomized pair-fed to the 100 µg DES group. Only 50 and 100 µg of DES resulted in significant reductions in water and food intakes, urinary volume, sodium, potassium, chloride and Na:K ratio. Pair-fed rats had similar decreases except for the Na:K ratio which remained normal. Except for the latter, all effects of high estrogen dosages can be attributed to reduced food intake. Estrogen did not alter glomerular filtration rate or serum electrolyte concentrations. Food deprivation caused a reduction in fluid exchange and electrolyte excretion in all except the ovariectomized animals which had an initial greater fluid turnover. Thus, DES, in high dosages, depressed the Na:K ratio in the ovariectomized rat, an effect which was independent of the electrolyte intake.
Interference in localization of I131 fibrinogen in rat tumors by anticoagulants
Authors: Shaeffer Joseph R.
Published: December 2017

A transplantable tumor of the rat, the Murphy-Sturm lymphosarcoma, was found to contain 15–25% of the administered radioactive dose 18 hr after intravenous injection of I131-labeled rat fibrinogen in a rat bearing a tumor in the 2–12 g wt. range. At this time the concentration of radioactivity per gram of tumor was found to be some 4–15 times that of such vascular organs as the liver and kidney, smaller tumors (2–5 g) localizing much more of the injected radioactive dose per gram than larger tumors (8–12 g). These tumors did not concentrate radioactivity after intravenous injection of either I131 γ-globulin or inorganic NaI131. The administration of heparin or warfarin in dosages adequate to completely inhibit the blood coagulation mechanism throughout the 18-hr experimental period decreased this specific tumor localization of I131 fibrinogen by 60–80%. It is concluded that the effect of heparin and warfarin on the coagulation mechanism is probably responsible for this decrease. A possible mechanism of tumor localization of I131 fibrinogen is discussed.
Mechanism of regulation of renal bicarbonate reabsorption by plasma CO2 tension
Authors: Goodman A. David , Fuisz Robert E.
Published: December 2017

It is known that the capacity of the kidney for bicarbonate reabsorption is a function of the systemic arterial pCO2. This relationship could be due to a direct effect of the level of arterial pCO2 on the kidney, or could be mediated by an extrarenal hormone. A surgical preparation has been devised in the dog whereby the pCO2 of the blood supplying the left kidney can be increased directly without significantly raising the pCO2 of the rest of the systemic arterial blood. It was found that a selective increase in left renal arterial pCO2 led to a rise in Tmhcohco3 of the left kidney. This rise in Tmhcohco3 was 73% of that produced by an equivalent elevation in the pCO2 of the whole systemic arterial system. It is concluded that the relationship between systemic arterial pCO2 and renal bicarbonate reabsorption is due in large measure to a direct effect of the level of arterial pCO2 on the kidney.
Some effects of urease administration on laboratory animals
Authors: Dang H. C. , Visek W. J.
Published: December 2017

A total of 850 mice, rats, guinea pigs, and rabbits were employed in the evaluation of the acute and subacute effects of crystalline jack bean urease following single or repeated administrations. The acute ld50 values in units per kilogram body weight for rats and mice by route of administration were: intraperitoneal (i.p.) 50; intravenous (i.v.) 20–25; and subcutaneous 50–58. The acute i.p. and i.v. ld50 values for rabbits were 25 and 6 units, respectively. For guinea pigs the i.p. ld50 was about 35 units. Growth of urease-treated rats and mice was equal to control whereas guinea pigs failed to grow as rapidly as their saline-treated controls. Urease-treated mice and rats had higher titers of serum antiurease than guinea pigs. Ammonia concentrations and urease activity in the gastrointestinal tract plus contents were markedly reduced in rats, mice, and guinea pigs indicating that antiurease entered the gastrointestinal tract and inhibited bacterial urease(s). No histopathological effects were noted. The toxicity was not cumulative and all survivors showed normal behavior.
Chemical concentration gradients and electrical properties of gastric mucosa
Authors: Harris John B. , Edelman Isidore S.
Published: December 2017

This study explored the possibility that each surface of the gastric epithelial cell contains ion transport systems contributing to the observed transmucosal potential difference ( Vt). The model proposes that Vt arises from a K+ and Cl– diffusion potential across the submucosal face of the epithelial cells in series with the potential generated by electrogenic transport of H+ and Cl– across the mucosal face. The bio-electric effects of changes in the ionic composition of the bathing media and the tissue composition data were used to test this hypothesis. Vt varied with the log of submucosal K+ at constant Cl– and with the log of submucosal Cl– at constant K+; the sum of the slopes averaged 50 mv. Simultaneous tenfold changes in K+ and Cl– in the submucosal solutions resulted in a 53-mv change in Vt, a reasonable agreement with the theoretical value of 58 mv for a system in which the total electrical conductance is given by the sum of the K+ and Cl– conductances. Alterations in Na+ at either surface had no appreciable effect on Vt. Chemical analysis of gastric mucosae and plasma revealed the predicted pattern of K+ (mucosa) > K+ (extracellular), Na+ (mucosa) < Na+ (extracellular), and Cl– (mucosa) < Cl– (extracellular).
Regional blood flow measurement in vivo for a definable geometry
Authors: Bacaner Marvin B. , Beck James S.
Published: December 2017

A radioisotope method for measuring regional blood flow in the intestine of the dog in vivo has been favorably compared with measurement by timed collection of total venous outflow. The necessary conditions are a continuous measure of arterial concentration and cumulative regional concentration of radioisotope, an experimentally definable region, and temporary complete retention of tracer. The derivation of the relations used suggests additional applications of the method to other regions of the body.
Renal interstitial hydrostatic pressure and sodium excretion during acute volume expansion in diabetic rats
Authors: Patel Kaushik P. , Carmines Pamela K.
Published: December 2017

Experiments were performed to test the hypothesis that the renal interstitial hydrostatic pressure (RIHP) response to acute volume expansion is suppressed in diabetes mellitus. Sprague-Dawley rats received streptozotocin (STZ rats; 65 mg/kg ip) or vehicle (Sham rats). Two weeks later, RIHP and Na+ excretion responses to acute graded volume expansion with isotonic saline were quantified under Inactin anesthesia (0.1 mg/kg ip). In Sham rats, acute graded volume expansion to 10% body wt produced increases in RIHP (Δ = 12.2 ± 2.4 mmHg), urine flow (Δ = 54 ± 8 μl · min−1 · g−1), and Na+ excretion (Δ = 11.5 ± 1.9 μeq · min−1 · g−1). In STZ rats, these volume expansion-induced responses were significantly blunted (RIHP by 50%, urine flow by 81%, and Na+excretion by 76%). Renal decapsulation eliminated the differences between STZ and Sham rats with regard to volume expansion-induced increases in RIHP, urine flow, and Na+ excretion. Renal denervation normalized the RIHP response to volume expansion and improved the diuretic and natriuretic responses in STZ rats. Moreover, diuretic and natriuretic responses to direct changes in RIHP (induced by renal interstitial volume expansion) were blunted in STZ rats. We conclude that diminished alterations in RIHP, as well as a reduced impact of RIHP on Na+ excretion, contribute to the impaired diuretic and natriuretic responses to acute volume expansion during the early stage of diabetes.
Early-age heat exposure affects skeletal muscle satellite cell proliferation and differentiation in chicks
Authors: Halevy Orna , Krispin Alon , Leshem Yael , McMurtry John P. , Yahav Shlomo
Published: December 2017

Exposure of young chicks to thermal conditioning (TC; i.e., 37°C for 24 h) resulted in significantly improved body and muscle growth at a later age. We hypothesized that TC causes an increase in satellite cell proliferation, necessary for further muscle hypertrophy. An immediate increase was observed in satellite cell DNA synthesis in culture and in vivo in response to TC of 3-day-old chicks to levels that were significantly higher than those of control chicks. This was accompanied by a marked induction of insulin-like growth factor-I (IFG-I), but not hepatocyte growth factor in the breast muscle. No significant difference between treatments in plasma IGF-I levels was observed. A marked elevation in muscle regulatory factors on day 5, followed by a decline in cell proliferation on day 6together with continuous high levels of IGF-I in the TC chick muscle may indicate accelerated cell differentiation. These data suggest a central role for IGF-I in the immediate stimulation of satellite cell myogenic processes in response to heat exposure.
Role of plasma ANG II in the excretion of acute sodium load in a bird with salt glands (Anas platyrhynchos)
Authors: Heinz Myriam K. , Gray David A.
Published: December 2017

This study was designed to further examine the role of plasma ANG II in the excretion of sodium in the Pekin duck, a bird with salt glands. Renal and extrarenal (salt gland) excretion of an intravenously administered isotonic saline load was monitored over a 4-h period in a group of eight birds under two conditions: the control condition, in which isotonic saline infusion decreased endogenous plasma ANG II from 102.6 to 16.5 pg/ml, and the experimental condition, in which ANG II suppression was prevented by intravenous infusion of a 3.5 ng · kg−1· min−1dose of synthetic ANG II. ANG II infusion significantly decreased the total sodium excretion (by 15%), primarily via an inhibition of salt gland output. The results suggest that ANG II suppression facilitates the excretion of an administered sodium load in birds with salt glands.
Altered phosphorylation and calcium sensitivity of cardiac myofibrillar proteins during sepsis
Authors: Wu Li-Ling , Tang Chaoshu , Liu Maw-Shung
Published: December 2017

Altered phosphorylation and Ca2+sensitivity of cardiac myofibrillar proteins during different phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture (CLP). The results show that phosphorylation of troponin I (TnI) was increased by 268% during the early phase (9 h after CLP) but decreased by 46% during the late phase (18 h after CLP) of sepsis. Phosphorylation of C protein was increased by 76% during the early phase but decreased by 41% during the late phase of sepsis. Phosphorylation of myosin light chain-2 (MLC-2) remained unaltered during the early phase but was decreased by 38% during the late phase of sepsis. Phosphorylation of TnT was unaffected during the progression of sepsis. The increases in the phosphorylation of TnI and C protein during early sepsis were associated with the decrease in the Ca2+sensitivity of myofilaments and the increases in myocardial changes in tension development (+dP/d tmax) and cAMP level. The decreases in the phosphorylation of TnI and C protein during late sepsis coincided with the declines in the activities of myofibrillar ATPase, Ca2+sensitivity of myofilaments, myocardial ±dP/d tmax, and cAMP content. The increases and the decreases in the phosphorylation of TnI and C protein, ±dP/d tmax, and the tissue cAMP level were sensitive to isoproterenol stimulation and propranolol inhibition. These findings suggest that alterations in the phosphorylation of myofibrillar proteins, such as TnI, C protein, and MLC-2, and changes in the activities and the Ca2+sensitivity of myofibrillar ATPase may contribute to the altered cardiac function during the progression of sepsis. Furthermore, the sepsis-induced alterations in the phosphorylation and Ca2+sensitivity of cardiac myofibrillar proteins were mediated via a β-adrenergic receptor pathway.
Increased pyruvate flux capacities account for diet-induced increases in gluconeogenesis in vitro
Authors: Bizeau Michael E. , Short Chiffon , Thresher Jeffrey S. , Commerford S. Renee , Willis Wayne T. , Pagliassotti Michael J.
Published: December 2017

High-fat (HF) and high-sucrose (SU) diets increase gluconeogenesis. The present study was designed to determine the contributions of pyruvate dehydrogenase, pyruvate carboxylase, phospho enolpyruvate carboxykinase (PEPCK), and pyruvate kinase fluxes to this accelerated gluconeogenesis (GNEO) in the absence and presence of fatty acids. Male Sprague-Dawley rats were fed an HF, SU, or starch (ST) diet for 1 wk, and hepatocytes or mitochondria were isolated. In the absence of palmitate, the tracer estimated rates of GNEO (nmol · min−1· mg−1) were elevated in hepatocytes isolated from SU (32.3 ± 1.8) and HF (35.4 ± 1.8) vs. ST (22.8 ± 1.5). Pyruvate carboxylase and PEPCK flux rates (nmol · min−1· mg−1) were increased in the SU (47.5 ± 2.2 and 34.8 ± 1.5) and HF (49.4 ± 1.8 and 38.2 ± 1.8) groups compared with the ST group (32.8 ± 3.2 and 44.3 ± 2.0). Palmitate (250–1,000 μM) stimulation of these fluxes was not significantly different among groups. Bromopalmitate, an inhibitor of fat oxidation, abolished differences in GNEO, pyruvate carboxylase, and PEPCK fluxes in HF and SU vs. ST. In isolated mitochondria, pyruvate carboxylation and palmitoyl carnitine oxidation were not significantly different among groups. The results of this study suggest that the increased gluconeogenic flux observed with HF and SU diets is associated with an increased pyruvate flux through pyruvate carboxylase and PEPCK. Moreover, the ability of bromopalmitate to normalize gluconeogenic fluxes suggests that endogenous fatty acids contribute to diet-induced increases in GNEO.
Differential sympathetic nerve and heart rate spectral effects of nonhypotensive lower body negative pressure
Authors: Floras John S. , Butler Gary C. , Ando Shin-Ichi , Brooks Steven C. , Pollard Michael J. , Picton Peter
Published: December 2017

Lower body negative pressure (LBNP; −5 and −15 mmHg) was applied to 14 men (mean age 44 yr) to test the hypothesis that reductions in preload without effect on stroke volume or blood pressure increase selectively muscle sympathetic nerve activity (MSNA), but not the ratio of low- to high-frequency harmonic component of spectral power (PL/PH), a coarse-graining power spectral estimate of sympathetic heart rate (HR) modulation. LBNP at −5 mmHg lowered central venous pressure and had no effect on stroke volume (Doppler) or systolic blood pressure but reduced vagal HR modulation. This latter finding, a manifestation of arterial baroreceptor unloading, refutes the concept that low levels of LBNP interrogate, selectively, cardiopulmonary reflexes. MSNA increased, whereas PL/PH and HR were unchanged. This discordance is consistent with selectivity of efferent sympathetic responses to nonhypotensive LBNP and with unloading of tonically active sympathoexcitatory atrial reflexes in some subjects. Hypotensive LBNP (−15 mmHg) increased MSNA and PL/PH, but there was no correlation between these changes within subjects. Therefore, HR variability has limited utility as an estimate of the magnitude of orthostatic changes in sympathetic discharge to muscle.
Force reduction uncoupled from pH and H2PO 4 − in rat gastrocnemius in vivo with continuous 2-Hz stimulation
Authors: Cieslar Julie H. , Dobson Geoffrey P.
Published: December 2017

The aim of this study was to examine the effect of the products of ATP hydrolysis on the fatigue process in rat gastrocnemius in vivo. Adult male Sprague-Dawley rats (300–400 g) were anesthetized and ventilated in a custom-built cradle fitted with a force transducer that could be placed into a 7-T NMR magnet. The muscle was stimulated continuously at 2 Hz for 20 min ( n = 7). Isometric twitch force increased in the first 4 min of stimulation accompanied by changes in twitch duration (20% increase in relaxation time). Prolonged relaxation was associated with changes in cytosolic pH (6.91 to 6.58), lactate (1.8 to 12.6 μmol/g wet wt), and H2PO[Formula: see text] (7.57 to 13.99 mM). After 4 min, relaxation time, pH, lactate, and H2PO[Formula: see text] returned toward control values as twitch force progressively decreased. No correlation was found between force decline (or twitch broadening) and total phosphate (3 to 23 mM), free [ADP] (18 to 95 μM), free [Mg2+] (0.58 to 0.96 mM), or free energy of ATP hydrolysis (−65 to −55 kJ/mol). We conclude that force decline is not due to increased pH and/or H2PO[Formula: see text] but to fatigue of the fast-twitch fibers, possibly linked to glycogen depletion and/or failure of nerve impulse transmission in these fibers.
Renal effects of nitric oxide synthase inhibition in conscious water-loaded dogs
Authors: Peterson Thomas V. , Emmeluth Claus , Bie Peter
Published: December 2017

The renal effects of the nitric oxide (NO) synthase inhibitor nitro-l-arginine methyl ester (l-NAME) were investigated in conscious dogs undergoing sustained water diuresis and replacement of urinary sodium losses. Experiments were performed with and without additional extracellular volume expansion (isotonic saline, 2% body wt). l-NAME (10 μg · kg−1· min−1) infused during water diuresis decreased urine flow (2.5 ± 0.2 to 1.5 ± 0.3 ml/min), free water clearance (1.9 ± 0.2 to 1.0 ± 0.2 ml/min), and sodium excretion (4.0 ± 1.7 to 2.1 ± 0.6 μmol/min). Arterial blood pressure increased from 112 ± 2 to 126 ± 3 mmHg, but creatinine clearance did not measurably change. Plasma endothelin and vasopressin concentrations and plasma renin activity (PRA) were unchanged. Urinary endothelin concentration increased (3.4 ± 0.8 to 6.2 ± 1.7 pg/ml), but the excretion rate remained constant. l-Arginine infusion (0.6 mg · kg−1· min−1) along withl-NAME abolished the renal effects but not the blood pressure increase. Volume expansion increased urine flow (2.5 ± 0.4 to 5.7 ± 0.5 ml/min) and sodium excretion (3.8 ± 1.6 to 76.5 ± 14.5 μmol/min). l-NAME attenuated the renal effects of volume expansion: urine flow increased to 2.8 ± 0.7 ml/min and sodium excretion to 34 ± 17 μmol/min. PRA decreased with control volume expansion but not during l-NAME. Urinary endothelin levels were elevated by l-NAME, decreased with volume expansion in all series, but excretion rate remained constant. Infusion of l-arginine partially reversed these effects of l-NAME. The results demonstrate that NO synthase inhibition increases blood pressure and blunts the renal responses to water and saline loading.
The small intestine is an important source of adrenomedullin release during polymicrobial sepsis
Authors: Zhou Mian , Chaudry Irshad H. , Wang Ping
Published: December 2017

Adrenomedullin (AM), a potent vasodilatory peptide, has recently been reported to be involved in the altered cardiovascular responses under various pathophysiological conditions. Although the increase in plasma AM levels is associated with upregulation of AM gene expression in various tissues, it remains unknown whether the gut is an important source of AM release under such conditions. To determine this, adult male rats were subjected to sepsis by cecal ligation and puncture (CLP) followed by fluid resuscitation. Systemic and portal blood samples were collected simultaneously at 10 and 20 h after CLP or sham operation. A portion of the jejunum was also harvested. Plasma and tissue levels of AM were then determined by RIA. The localization of AM in the intestinal tissue was examined using immunohistochemistry. In an additional group of normal rats, synthetic rat AM (8.5 μg/kg body wt) was infused for 15 min at a constant rate via the portal vein (which produces a similar level of AM as observed during sepsis). Cardiac output, stroke volume, total peripheral resistance, and microvascular blood flow in various organs were determined before and 30 min after AM administration. The results indicate that AM levels in portal blood were significantly higher than in systemic blood at 10 and 20 h after CLP. Intestinal AM was also markedly elevated. Immunohistochemical visualization shows that AM immunostainings were localized in the mucosa, submucosa, and intestinal nerve fibers, and they were increased at 10–20 h post-CLP. Because AM-immunopositive nerve fibers increase in the gut during sepsis, a nerve pathway may be involved in the regulation of vascular reactivity by this peptide. Moreover, intraportal administration of AM increased cardiac output, stroke volume, and microvascular blood flow in the liver, kidney, small intestine, and spleen. In contrast, total peripheral resistance was significantly reduced. Thus the gut plays an important role in increasing the levels of circulating AM during the progression of sepsis. Gut-derived AM appears to be a major factor in initiating the hyperdynamic response after the onset of sepsis.
Temperature-sensitive properties of rat suprachiasmatic nucleus neurons
Authors: Burgoon Penny W. , Boulant Jack A.
Published: December 2017

The hypothalamic suprachiasmatic nucleus (SCN) contains a heterogeneous population of neurons, some of which are temperature sensitive in their firing rate activity. Neuronal thermosensitivity may provide cues that synchronize the circadian clock. In addition, through synaptic inhibition on nearby cells, thermosensitive neurons may provide temperature compensation to other SCN neurons, enabling postsynaptic neurons to maintain a constant firing rate despite changes in temperature. To identify mechanisms of neuronal thermosensitivity, whole cell patch recordings monitored resting and transient potentials of SCN neurons in rat hypothalamic tissue slices during changes in temperature. Firing rate temperature sensitivity is not due to thermally dependent changes in the resting membrane potential, action potential threshold, or amplitude of the fast afterhyperpolarizing potential (AHP). The primary mechanism of neuronal thermosensitivity resides in the depolarizing prepotential, which is the slow depolarization that occurs prior to the membrane potential reaching threshold. In thermosensitive neurons, warming increases the prepotential's rate of depolarization, such that threshold is reached sooner. This shortens the interspike interval and increases the firing rate. In some SCN neurons, the slow component of the AHP provides an additional mechanism for thermosensitivity. In these neurons, warming causes the slow AHP to begin at a more depolarized level, and this, in turn, shortens the interspike interval to increase firing rate.
Volume-activated trimethylamine oxide efflux in red blood cells of spiny dogfish (Squalus acanthias)
Authors: Koomoa Dana-Lynn T. , Musch Mark W. , Vaz MacLean Ainsley , Goldstein Leon
Published: December 2017

The aims of this study were to determine the pathway of swelling-activated trimethylamine oxide (TMAO) efflux and its regulation in spiny dogfish ( Squalus acanthias) red blood cells and compare the characteristics of this efflux pathway with the volume-activated osmolyte (taurine) channel present in erythrocytes of fishes. The characteristics of the TMAO efflux pathway were similar to those of the taurine efflux pathway. The swelling-activated effluxes of both TMAO and taurine were significantly inhibited by known anion transport inhibitors (DIDS and niflumic acid) and by the general channel inhibitor quinine. Volume expansion by hypotonicity, ethylene glycol, and diethyl urea activated both TMAO and taurine effluxes similarly. Volume expansion by hypotonicity, ethylene glycol, and diethyl urea also stimulated the activity of tyrosine kinases p72syk and p56lyn, although the stimulations by the latter two treatments were less than by hypotonicity. The volume activations of both TMAO and taurine effluxes were inhibited by tyrosine kinase inhibitors, suggesting that activation of tyrosine kinases may play a role in activating the osmolyte effluxes. These results indicate that the volume-activated TMAO efflux occurs via the organic osmolyte (taurine) channel and may be regulated by the volume activation of tyrosine kinases.
Effect of cortisol on the physiology of cultured pavement cell epithelia from freshwater trout gills
Authors: Kelly Scott P. , Wood Chris M.
Published: December 2017

Cortisol had dose-dependent effects on the electrophysiological, permeability, and ion-transporting properties of cultured pavement cell epithelia derived from freshwater rainbow trout gills and grown on cell culture filter supports. Under both symmetrical (L15 media apical/L15 media basolateral) and asymmetrical (freshwater apical/L15 media basolateral) culture conditions, cortisol treatment elevated transepithelial resistance, whereas permeability of epithelia to a paracellular permeability marker (polyethylene glycol-4000) decreased. Cortisol did not alter the Na+-K+-ATPase activity or the total protein content of the cultured preparations. During 24-h exposure to asymmetrical conditions, the net loss rates of both Na+and Cl−to the water decreased with increasing cortisol dose, an important adaptation to dilute media. Unidirectional Na+and Cl−flux measurements and the application of the Ussing flux-ratio criterion revealed cortisol-induced active uptake of both Na+and Cl−under symmetrical culture conditions together with an increase in transepithelial potential (positive on the basolateral side). Under asymmetrical conditions, cortisol did not promote active ion transport across the epithelium. These experiments provide evidence for the direct action of cortisol on cultured pavement cell epithelia and, in particular, emphasize the importance of cortisol for limiting epithelial permeability.
Estradiol impairs hyposmoregulatory capacity in the euryhaline tilapia,Oreochromis mossambicus
Authors: Vijayan Mathilakath M. , Takemura Akihiro , Mommsen Thomas P.
Published: December 2017

Freshwater (FW)-adapted tilapia ( Oreochromis mossambicus) were treated with estradiol (E2) for 4 days to stimulate protein synthesis and sampled at 0, 4, and 24 h after exposure to 50% seawater (SW). E2increased circulating vitellogenin (VTG) levels in large amounts, indicative of unusually high rates of hepatic protein synthesis. E2treatment prevented the recovery of plasma osmolality in 50% SW that was evident in the sham group. Plasma sodium concentration was significantly elevated with E2in FW, but the levels did not change in 50% SW. Gill Na+-K+-ATPase activity was significantly lower in the E2group compared with sham-injected tilapia in 50% SW. No significant differences were noted in plasma cortisol, thyroxine, triiodothyronine, or glucose concentration with E2in 50% SW. E2significantly lowered several key liver enzyme activities and also decreased gill lactate dehydrogenase and malate dehydrogenase activities over a 24-h period. Together, our results suggest that E2impairs ion regulation in tilapia, partially mediated by a decreased metabolic capacity in liver and gill. The decreased tissue metabolic capacity is likely due to E2-induced energy repartitioning processes that are geared toward VTG synthesis at the expense of other energy-demanding pathways.
Estradiol increases glucagon's satiating potency in ovariectomized rats
Authors: Geary Nori , Asarian Lori
Published: December 2017

Estradiol decreases meal size, food intake, and body weight in female rats. To investigate whether these effects of estradiol involve a change in the sensitivity of the signaling pathway through which pancreatic glucagon released during meals contributes to meal termination (satiation), glucagon or glucagon antibodies were infused via the hepatic portal vein in ovariectomized rats that were chronically treated with estradiol benzoate (2 μg/day sc) or vehicle alone (100 μl sesame oil). Infusions began at 1 h after dark onset, as rats were refed after 7 h of food deprivation. Glucagon (3 μg/min for 30 min) decreased feeding during the initial 45 min of food access in both groups of rats, but the inhibition was significantly greater in estradiol- than in oil-treated rats. Similarly, antagonism of endogenous glucagon by infusion of glucagon antibodies (a dose neutralizing 3 ng of glucagon in vitro during the first 3 min of refeeding) increased feeding significantly more in estradiol- than in oil-treated rats. These data indicate that an increase in the activity of the endogenous glucagon satiation-signaling pathway may be part of the mechanism for estradiol's inhibitory effect on feeding.
Selective effect of tempol on renal medullary hemodynamics in spontaneously hypertensive rats
Authors: Feng Ming-Guo , Dukacz Stephen A. W. , Kline Robert L.
Published: December 2017

The present study assessed the short- and long-term effect of tempol, a membrane-permeable mimetic of superoxide dismutase, on renal medullary hemodynamics in spontaneously hypertensive rats (SHR). Tempol was given in the drinking water (1 mM) for 4 days or 7 wk (4–11 wk of age), and medullary blood flow (MBF) was measured over a wide range of renal arterial pressure by means of laser-Doppler flowmetry in anesthetized rats. In addition, the response of the medullary circulation to angiotensin II (5–50 ng · kg−1 · min−1 iv) was determined in SHR treated for 4 days with tempol. Compared with control SHR, short- and long-term treatment with tempol decreased arterial pressure by ∼20 mmHg and increased MBF by 35–50% without altering total renal blood flow (RBF) or autoregulation of RBF. Angiotensin II decreased RBF and MBF dose dependently (∼30% at the highest dose) in control SHR. In SHR treated with tempol, angiotensin II decreased RBF (∼30% at the highest dose) but did not alter MBF significantly. These data indicate that the antihypertensive effect of short- and long-term administration of tempol in SHR is associated with a selective increase in MBF. Tempol also reduced the sensitivity of MBF to angiotensin II. Taken together, these data support the idea that tempol enhances vasodilator mechanisms of the medullary circulation, possibly by interacting with the nitric oxide system. Increased MBF and reduced sensitivity of MBF to angiotensin II may contribute to the antihypertensive action of tempol in SHR.
Parametric analysis of gastric distension responses in the parabrachial nucleus
Authors: Baird John-Paul , Travers Joseph B. , Travers Susan P.
Published: December 2017

The parabrachial nucleus (PBN) is regarded as an important locus for the processing and integration of sensory inputs from oral, gastrointestinal, and postabsorptive receptor sites and is thus thought to play an important role in regulating food intake. Gastric distension is an important satiation cue; however, such responses have been qualitatively characterized only over a limited area of the PBN. To more fully characterize gastric distension responses throughout the PBN, the responses of single units to gastric distension were tested using computer-controlled balloon inflation (3–18 ml air) in pentobarbital sodium- and/or urethan-anesthetized male rats. Distension-responsive neurons were indeed distributed throughout the nucleus from rostral areas typically considered to be visceral to more caudal areas associated with gustatory function, providing further anatomical support for the hypothesis that the PBN integrates taste and visceral signals that control feeding. Most PBN neurons had thresholds of 6 ml or less, similar to vagal afferent fibers. However, in contrast to the periphery, there were both excitatory and inhibitory responses. Increases in volume were associated with two distinct effects. First, as volume increased, the response rate increased; second, the duration of the response increased. In fact, in a subset of cells, responses to gastric distension lasted well beyond the stimulation period, particularly at larger volumes. Prolonged gastric distension responses are not common in the periphery and may constitute a central mechanism that contributes to satiation processes.
Naloxone's effect on meal microstructure of sucrose and cornstarch diets
Authors: Glass Michael J. , Grace Martha K. , Cleary James P. , Billington Charles J. , Levine Allen S.
Published: December 2017

The opioid receptor antagonist naloxone decreases consumption of high-sucrose diets but does not reduce cornstarch diet intake in energy-restricted rats. Sucrose-fed rats eat at a much higher rate, consuming more food than cornstarch-fed rats. We examined meal microstructure using an automated weighing system in food-restricted rats eating either a high-sucrose or high-cornstarch diet. Sucrose-fed rats exhibited a higher rate of eating during their first meal compared with cornstarch-fed rats (0.34 vs. 0.20 g/min, respectively). However, naloxone did not reduce eating rate in either group. Naloxone decreased the size of the first meal in both diet groups by shortening the length of the meal. Naloxone's anorectic effect was more potent in the sucrose-fed rats. These results indicate that naloxone's heightened anorectic effect on sucrose diet consumption is not “rate dependent.” Naloxone's anorectic actions may be modulated by two conditions, the sensory properties of food and the energy state of the animal. Thus the elevated anorectic potency of naloxone in energy-restricted sucrose-fed rats may reflect actions on neural systems that mediate orosensory and/or postingestive signals.
Behavioral thermoregulation in obese and lean Zucker rats in a thermal gradient
Authors: Maskrey Michael , Wiggins Paul R. , Frappell Peter B.
Published: December 2017

Genetically obese Zucker (Z) rats have been reported to display a body core temperature (Tb) that is consistently below that of their lean littermates. We asked the question whether the lower Tb was a result of deficits in thermoregulation or a downward resetting of the set point for Tb. For a period of 45 consecutive hours, lean and obese Z rats were free to move within a thermal gradient with an ambient temperature (Ta) range of 15–35°C, while subjected to a 12:12-h light-dark cycle. Tb was measured using a miniature radio transmitter implanted within the peritoneal cavity. Oxygen consumption (V˙o 2) was measured using an open flow technique. Movements and most frequently occupied position in the gradient (preferred Ta) were recorded using a series of infrared phototransmitters. Obese Z rats were compared with lean Z rats matched for either age (A) or body mass (M). Our results show that obese Z rats have a lower Tb[37.1 ± 0.1°C (SD) vs. 37.3 ± 0.1°C, P< 0.001] and a lower V˙o 2 (25.3 ± 1.9 ml · kg−1 · h−1) than lean controls [33.1 ± 3.7 (A) and 33.9 ± 3.9 (M) ml · kg−1 · h−1, P < 0.001]. Also, the obese Z rats consistently chose to occupy a cooler Ta [20.9 ± 0.6°C vs. 22.7 ± 0.6°C (A) and 22.5 ± 0.7°C (M), P < 0.001] in the thermal gradient. This suggests a lower set point for Tb in the obese Z rat, as they refused the option to select a warmer Ta that might allow them to counteract any thermoregulatory deficiency that could lead to a low Tb. Although all rats followed a definite circadian rhythm for both Tb and V˙o 2, there was no discernible circadian pattern for preferred Ta in either obese or lean rats. Obese Z rats tended to show a far less definite light-dark activity cycle compared with lean rats.
Ischemia-induced structural change in SR Ca2+-ATPase is associated with reduced enzyme activity in rat muscle
Authors: Tupling R. , Green H. , Senisterra G. , Lepock J. , McKee N.
Published: December 2017

In this study, we employed an in vivo model of prolonged ischemia in rat skeletal muscle to investigate the hypothesis that structural modifications to the sarcoplasmic reticulum (SR) Ca2+-ATPase can explain the alterations in Ca2+-ATPase activity that occur with ischemia. To induce total ischemia, a tourniquet was placed around the upper hindlimb in 27 female Sprague-Dawley rats weighing 256 ± 6.7 g (mean ± SE) and was inflated to 350 mmHg for 4 h. The contralateral limb served as control (C) to the ischemic limb (I), and the limbs of animals killed immediately after anesthetization served as a double control (CC). Mixed gastrocnemius and tibialis anterior muscles were sampled and used for SR vesicle preparation. Maximal Ca2+-ATPase activity (μmol · g protein−1· min−1) of C (15,802 ± 1,246) and I (11,609 ± 1,029) was 90 and 73% ( P < 0.05) of CC (17,562 ± 1,682), respectively. No differences were found between groups in either the Hill coefficient or the free Ca2+at half-maximal activity. The fluorescent probes, FITC and N-cyclohexyl- N′-(dimethylamino-α-naphthyl) carbodiimide, used to assess structural alterations in the regions of the ATP binding site and the Ca2+binding sites of the Ca2+-ATPase, respectively, indicated a 26% reduction ( P < 0.05) in FITC binding capacity (absolute units) in I (0.22 ± 0.01) compared with CC (0.29 ± 0.02) and C (0.29 ± 0.03). Our results suggest that the reduction in maximal SR Ca2+-ATPase activity in SR vesicles with ischemia is related to structural modification in the region of the nucleotide binding domain by mechanisms that are as yet unclear.
Bladder injection of “naked”hSlo/pcDNA3 ameliorates detrusor hyperactivity in obstructed rats in vivo
Authors: Christ G. J. , Day N. S. , Day M. , Santizo C. , Zhao W. , Sclafani T. , Zinman J. , Hsieh K. , Venkateswarlu K. , Valcic M. , Melman A.
Published: December 2017

The goal of these studies was to examine the potential utility of bladder instilled K+channel gene therapy with hSlo cDNA (i.e., the maxi-K channel) to ameliorate bladder overactivity in a rat model of partial urinary outlet obstruction. Twenty-two female Sprague-Dawley rats were subjected to partial urethral (i.e., outlet) obstruction, with 17 sham-operated control rats run in parallel. After 6 wk of obstruction, suprapubic catheters were surgically placed in the dome of the bladder in all rats. Twelve obstructed rats received bladder instillation of 100 μg of hSlo/pcDNA in 1 ml PBS during catheterization, and another 10 obstructed rats received 1 ml PBS (7 rats) or 1 ml PBS containing pcDNA only (3 rats). Two days after surgery cystometry was performed on all animals to examine the characteristics of the micturition reflex in conscious and unrestrained rats. Obstruction was associated with a three- to fourfold increase in bladder weight and alterations in virtually every micturition parameter estimate. PBS-injected obstructed rats routinely displayed spontaneous bladder contractions between micturitions. In contrast, hSloinjection eliminated the obstruction-associated bladder hyperactivity, without detectably affecting any other cystometric parameter. Presumably, expression of hSlo in rat bladder functionally antagonizes the increased contractility normally observed in obstructed animals and thereby ameliorates bladder overactivity. These initial observations indicate a potential utility of gene therapy for urinary incontinence.