bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of stretch on mechanical and electrical properties of cardiac muscle
Authors: Penefsky Zia J. , Hoffman Brian F.
Published: December 2017

A comparative study was made of effects of stretch on cat papillary muscle and auricle strips, hamster ventricular wall, ground squirrel ventricular strip, chicken auricle and ventricle, terrapin auricle and ventricle strips, and carp ventricle. In all species mild stretch increased contractile tension, excessive stretch decreased it, and velocity of conduction was constant with mild stretch but decreased with excessive stretch. In homeotherms under mild stretch, contraction time was unchanged and increased contractile tension was accompanied by increase in velocity of contraction. Under excessive stretch contraction time increased despite decreasing contractile tension. In poikilotherms contraction time and contractile tension were increased by mild stretch. Contraction time decreased with excessive stretch. Stretch increased relaxation time in all species. The evidence suggests that decrease in contractile tension with stretch is related, at least in the initial phases, to a change in excitability and conduction. In all species mild stretch was without effect on transmembrane action potentials, whereas at excessive stretch resting potentials and overshoot declined and rise time of the action potential was greatly increased. At excessive stretch surface-recorded potentials exhibited polyphasic deflections. All observed responses to stretch were reversible. Immediately after stretch the fibers were slightly elongated but developed a higher maximal contractile tension, and contraction time also was slightly increased.
Micropuncture study of renal tubular reabsorption of calcium in normal rodents
Authors: Lassiter William E. , Gottschalk Carl W. , Mylle Margaret
Published: December 2017

Anesthetized rats and hamsters were given Ca45 intravenously, and fluid was subsequently collected by micropuncture from glomeruli and surface tubules in the rats, and from loops of Henle in the hamsters. In nondiuretic animals, fluid:plasma calcium ratios averaged 0.71 in the glomerulus; 0.76 in the proximal tubule; 2.0 in the loop of Henle; 0.47 in the distal convolution; and 0.9 in ureteral urine. In mannitol diuresis, the calcium ratio of glomerular fluid was unchanged, but ratios as low as 0.21 were noted in the proximal tubule. In this circumstance, the average proximal ratio was 0.61, and the distal ratio 0.07. These results indicate active transport of calcium out of all major parts of the nephron, with the bulk of calcium reabsorption occurring in the convoluted portion of the proximal tubule. Furthermore, the pattern of tubular reabsorption of calcium is similar to that of sodium, suggesting that the two are related.
Electrolyte concentrations in saliva of the goat under various conditions
Authors: Komi Nobuhiko , Snyder William H.
Published: December 2017

The concentrations of sodium, potassium, and chloride in the saliva of the goat are reported for the first time. The parotid duct of several animals was cannulated with polyethylene tubing and a stable flow of saliva obtained for many weeks. Variations in the concentrations under normal living conditions (resting, ruminating, eating, and the like) are given. Certain additional conclusions appear significant. Partial obstruction of the parotid flow, minor infection of the gland, and the minor stress of strapping the animal to a table produces an immediate elevation of the chloride level with minimal alterations in the other electrolytes. The effect of major stress (abdominal operation) is a markedly lowered volume, greatly reduced concentrations of sodium and chloride, and strikingly elevated levels of potassium, over a period of several days. These alterations of function of the parotid secretions are an index of the basic metabolic changes accompanying major stress.
Action of sex steroids on the electrical and mechanical properties of rat atrium
Authors: Gimeno Alvaro L. , Gimeno Martha F. , Webb J. Leyden
Published: December 2017

The simultaneous effects of estradiol, testosterone, and progesterone on the electrical and mechanical characteristics of atrial cells were examined. Intracellular potentials were determined using microelectrodes; the mechanical activity was recorded from a strain gauge. Testosterone from 10–6 to 10–5 m produced a marked stimulation in normally contracting atria; while similar concentrations of progesterone and estradiol produced only contractile depression. All three sex steroids exerted a definite effect on the electrical characteristics, namely a reduction in the rates of depolarization and repolarization, without altering the magnitudes of the resting or action potentials appreciably. As a result, there is an increase in the duration and area of the action potential. They also slowed the conduction rate and increased the latent period, effects presumably associated with the slowed depolarization. The marked reduction in the rates of depolarization and repolarization is believed to be due to decreases in the ionic fluxes brought about by reducing the ionic permeability of the cardiac cell membranes. The effects are similar to those produced by antidysrhythmic drugs and may explain certain observations on the relation of cardiac excitability to steroid levels.
Intracellularly recorded responses of nerve cells to oxygen deprivation
Authors: Nelson P. G. , Frank K.
Published: December 2017

Transmembrane potentials of cat motoneuron somata were recorded with concentric microelectrodes (one inside and one outside, 20–40 µ apart) during several minutes of anoxia by artificial respiration with nitrogen or by asphyxia. Both large and small changes in membrane potential—some spontaneously reversible—were seen following .5–5 min of anoxia or asphyxia. Most large and many smaller changes were correlated with transient blood pressure changes. Sometimes membrane potential could be restored by mechanical adjustment of the micropipette. Especially when blood pressure was stabilized with an infusion of hexamethonium chloride, some motoneurons could withstand 4–5 min of anoxia or asphyxia with membrane potential changes of no more than 2–5 mv, close to the limit of significance with this technique. Some small potential changes may be the direct effect of hypoxia on motoneuron membrane or of a change in interneuron background activity, but after eliminating the effects of electrode movement the motoneuron is remarkably insensitive to anoxia.
In vitro inhibition of pituitary prolactin synthesis and release by hypothalamic extract
Authors: Talwalker P. K. , Ratner A. , Meites J.
Published: December 2017

When rat anterior pituitary (AP) was incubated at 37.5 C in a Dubnoff metabolic shaker for 2 hr, 169% more prolactin was found in the combined medium and AP than in nonincubated AP. When AP was incubated together with homogenate or acid extract of rat hypothalamus, prolactin levels in the medium and AP were markedly decreased (36–75%), indicating inhibition of synthesis and release. Acid extract of rat cerebral cortex had no effect on prolactin synthesis or release. Incubation of ovine or rat prolactin, with or without hypothalamus, did not decrease prolactin activity, demonstrating that hypothalamic inhibition of AP prolactin production was not due to hormone inactivation. Acetylcholine, epinephrine, norepinephrine, serotonin, histamine, substance P, oxytocin, and arginine or lysine vasopressin had no effect on AP prolactin release. These results indicate that the hypothalamus contains a factor(s) which inhibits synthesis and release of prolactin by the rat AP in vitro, and this factor(s) is not any of the recognized neurohumors in the hypothalamus.
Relationship between gastric secretion and behavior in chronic fistula rats
Authors: Komarov S. A. , Bralow S. P. , Shay H. , Boyd E.
Published: December 2017

Variations in several parameters of basal gastric secretion and in the behavior index determined in arbitrary rank units were studied in three groups of rats with chronic gastric fistula. There was an impressive similarity between the groups particularly in the patterns of variation during the 6 hr of observation. Volume and outputs of acid, pepsin, and chloride tended to decrease; a negative linear regression on hours was always significant but significant concave up parabolas often better fitted the data. Concentrations of acid and chloride increased significantly during an average experiment either linearly or in conformity with concave down parabolas. Lower concentrations of acid and chloride occurred concomitant with increases in volume and were considered due to salivary contamination associated with a higher behavior index. All above variations in secretion exhibited a significant linear correlation with variations in behavior index. Pepsin concentrations tended to decrease but were not significantly associated with behavior index. As a rule, there were significant differences among animals within groups, but none among the means of replicate experiments.
Stimulatory action of insulin on leucine uptake and metabolism in adipose tissue
Authors: Goodman H. Maurice
Published: December 2017

Epididymal fat incubated in the presence of glucose and dl-leucine-2-C14 incorporated C14 into fatty acids and CO2. Insulin at physiological concentrations increased leucine uptake and conversion to fatty acids and usually decreased oxidation to C14O2. In the absence of glucose, lipogenesis was sharply curtailed, but oxidation of leucine to C14O2 was unchanged. In this situation, insulin failed to increase lipogenesis from leucine, although its stimulatory action on leucine uptake remained. Virtually all the leucine C14 taken up under the influence of insulin now appeared as C14O2. Insulin similarly increased the uptake and conversion of acetate-2-C14 to fatty acids and decreased C14O2 production in the presence of glucose but not in its absence. Addition of α-aminoisobutyric acid to the medium blocked the stimulatory effect of insulin on leucine uptake. From these observations it is suggested that insulin may affect the synthesis of fatty acids from leucine in two ways: directly by increasing the transport of leucine into the cell and indirectly by increasing the availability of glucose and hence channeling the acetate derived from leucine into fatty acids.
Metabolism of free fatty acids by myocardium and kidney
Authors: Gold Martin , Spitzer John J.
Published: December 2017

The myocardial and renal removal and oxidation of plasma free fatty acids (FFA) were studied in dogs receiving an infusion of I-C14-palmitate, oleate, linoleate, or octanoate. The myocardium extracted about 40% of the total arterial FFA, and some was oxidized to CO2. Blood C14O2 was consistently higher in the coronary sinus than in the artery. The specific activity of the coronary sinus C14O2 was higher than that of the arterial C14O2 in dogs infused with long-chain fatty acids. The specific activity of arterial C14O2 was higher than that of the coronary sinus C14O2 when octanoate was infused. There were no differences observed in FFA extraction and C14O2 production among the different groups of animals receiving the various long-chain fatty acids. In gas chromatographic studies palmitic acid was the only FFA with a consistent net removal by the kidney. Approximately 9% of the arterial radiopalmitate was removed by this organ in dogs receiving infusions of palmitic acid-1-C14. Simultaneously, C14O2 was produced by the kidney. A consistent removal of oleate-1-C14 or a significant production of C14O2 was not found. Infusion of octanoate-1-C14 led to a marked release of C14O2 by the kidney, with greatly increased CO2 specific activity in the renal vein.
Aspects of circadian periodic changes in phosphorus metabolism in mice
Authors: Nelson Walter
Published: December 2017

Kinetic studies on the P32 content of mouse brain phosphorus fractions following the intraperitoneal injection of P32-labeled orthophosphate were performed during two selected segments of the 24-hr time scale. The results of these studies suggest that the circadian periodicity in relative specific activity of brain phospholipids is probably a consequence of a variation in the extent of P32 incorporation into brain inorganic phosphate and is not indicative of a periodicity in the rate of intermediary phospholipid metabolism. Data on the postinjection time course of the specific activities of plasma inorganic phosphate, liver inorganic phosphate, and liver phospholipid suggest a similar explanation for the circadian periodic changes in relative specific activity of liver phospholipids. A circadian rhythm of inorganic phosphate concentration in mouse plasma is demonstrated. Consideration of a mathematical model suggests that the observed within-day variation in P32 distribution and the circadian periodicity of phospholipid relative specific activity in liver and brain are a consequence of this periodicity in plasma phosphate content. A significant within-day variation in total phosphorus content of liver was observed. The disturbance of mice incident to P32 injection has a marked effect on the plasma content of inorganic phosphate and corticosterone.
Blood flow rates of intact and regenerated rat adrenals during stress
Authors: Kolthoff Norma J. , Macchi I. A. , Wyman Leland C.
Published: December 2017

Blood flow rates of intact rat adrenal glands and 30-day regenerated mesenteric transplants or enucleates were determined before and during stress. Venous flow rates were measured directly, and adrenal venous plasma and glandular corticoids were measured fluorimetrically. Arterial flow was determined by cardiac output fractionation employing Rb86 before and after 4-hr exposure to 4 C. In rats subjected to laparotomy, venous flow rate from regenerated enucleated glands was 42% less than that from intact glands, and the plasma corticoid level was 29% lower, while the glandular level was 33% higher. Arterial inflow of intact adrenals, transplants, and enucleates was approximately the same without stress and increased by similar amounts during cold stress. The ratio of adrenal outflow-to-inflow during stress was lower for regenerated than for intact glands. These results suggest an adrenal vascular abnormality on the venous side of regenerated tissue which prevents release of corticoids into the systemic circulation at a normal rate.
Vaginal physiological changes in a model of sexual arousal in anesthetized rats
Authors: Giuliano François , Allard Julien , Compagnie Sandrine , Alexandre Laurent , Droupy Stéphane , Bernabe Jacques
Published: December 2017

The understanding of the pathophysiology of female sexual dysfunction suffers from the lack of a convenient model for the study of female genital sexual response. In this study, systemic arterial blood pressure (BP) as well as partial oxygen tension, temperature, and blood engorgement of the vagina [using laser-Doppler flowmetry in arbitrary units (AU)] were measured in anesthetized, ovariectomized (1 wk before the start of the experiment) female rats. Vaginal sexual arousal was replicated by electrical stimulation of the pelvic nerve (PNS). PNS induced reproducible increases in the different vaginal parameters (from baseline value, respectively: 16 ± 10 to 30 ± 12 mmHg; 34.9 ± 0.6 to 36 ± 0.6°C; 450 ± 196 to 1,500 ± 360 AU; P < 0.05, paired t-test) and BP (90 ± 7 to 123 ± 13 mmHg, P < 0.05, paired t-test). Vaginal vascular resistance was significantly decreased during PNS (from 0.23 ± 0.15 to 0.08 ± 0.02 mmHg/AU). Vaginal wall tension was also measured with a force transducer. PNS induced an increase in vaginal wall tension (1.0 ± 0.2 g), followed by a decrease under the prestimulation value. Intravenous atropine sulfate (1 mg/kg) injection abolished the increase in vaginal wall tension without significantly affecting vaginal vascular resistance. Intravenous vercuronium bromide (2 mg/kg) injection abolished the decrease in vaginal wall tension. Concomitant electrical stimulation of the paravertebral sympathetic chain inhibited vaginal response induced by PNS. Electrical stimulation of the medial preoptic area of the hypothalamus induced a response qualitatively equivalent to PNS with a significant decrease of vaginal vascular resistance. These data support that vaginal contractions involve both smooth and striated muscles and indicate that neural control of vaginal sexual arousal have great similarities in male and female rats.
Role of the hepatic function in the development of the pyrogenic tolerance to muramyl dipeptide
Authors: Ferreira Márcia E. S. , Coelho Márcio M. , Pelá Irene R.
Published: December 2017

We have demonstrated that the hepatic function may have an important role in the development of tolerance to the pyrogenic effect induced by endotoxin. To further investigate if the role of the hepatic function in the development of tolerance also extends to that induced by other pyrogenic stimuli, we investigated the effect of galactosamine, a specific inhibitor of the hepatic protein synthesis, on the development of tolerance to the pyrogenic effect induced by muramyl dipeptide (MDP) in rats. Pyrogenic tolerance was observed after the second intravenous or intraperitoneal injection of MDP (500 μg/kg), 24 h after the first injection, similar to what was observed with endotoxin. Pyrogenic tolerance was abolished when galactosamine (300 mg/kg ip) was injected simultaneously with MDP (500 μg/kg iv) on the first day. When uridine (600 mg/kg ip) was administered simultaneously with galactosamine (300 mg/kg ip) and the first injection of MDP (500 μg/kg ip), pyrogenic tolerance was again observed after the second injection of the peptidoglycan. In conclusion, the hepatic function may not be important only for the development of tolerance to endotoxin, but also to a totally different pyrogenic stimulus such as MDP.
Postprandial neuronal activation in the nucleus of the solitary tract is partly mediated by CCK-A receptors
Authors: Glatzle Jörg , Kreis Martin E. , Kawano Kazuya , Raybould Helen E. , Zittel Tilman T.
Published: December 2017

CCK-A receptors and neurons of the nucleus of the solitary tract (NTS) are involved in the regulation of food intake, and in rats, there is evidence for involvement of an intestinal vagal afferent pathway. Studies investigating the role of CCK-A receptors in activation of NTS neurons using highly selective CCK-A receptor agonists and antagonists have yielded conflicting data. In the present study, we investigated CCK-induced and postprandial activation of NTS neurons, together with food intake studies, in CCK-A receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats. Activated NTS neurons were detected using immunohistological staining for c-Fos protein. Exogenous CCK increased the number of c-Fos protein-positive cells in the NTS of Sprague-Dawley and CCK-A receptor-intact Long-Evans Tokushima Otsuka (LETO) rats but had no effect in CCK-A receptor-deficient OLETF rats. Food intake-induced c-Fos protein expression in NTS neurons was significantly reduced in CCK-A receptor-deficient OLETF rats compared with Sprague-Dawley or LETO rats. Postprandial c-Fos protein expression in the NTS was also significantly decreased after pretreatment with the CCK-A receptor antagonist MK329 after both short- and long-term fasting periods. Exogenous CCK decreased cumulative food intake in Sprague-Dawley and LETO rats but not in OLETF rats. These data demonstrate that CCK-A receptors are involved in the CCK- and food-induced c-Fos protein expression in the NTS. Taken together with the results of the food intake studies, this suggests that activation of CCK-A receptors is involved in the postprandial activation of NTS neurons and in the regulation of food intake.
Interaction of NaCl and behavioral stress on endogenous sodium pump ligands in rats
Authors: Fedorova Olga V. , Anderson David E. , Lakatta Edward G. , Bagrov Alexei Y.
Published: December 2017

Our study investigated the hypothesis that the combination of a high NaCl diet and social isolation stress would increase systolic blood pressure (SBP) and endogenous sodium pump ligands (SPL), ouabainlike compound (OLC), and marinobufagenin (MBG). Excretion of MBG and OLC, SBP, and organ weights were studied in four groups ( n = 8) of male Fisher 344 × Norwegian brown rats: controls, socially isolated (Iso), 4% NaCl diet (Salt), and the combination of Salt and Iso (Iso+Salt). In Salt, MBG excretion increased by 78% ( P < 0.01), whereas SBP and OLC remained unchanged. In Iso, SBP and MBG did not change, but OLC peaked on day 1. In the Iso+Salt, SBP increased by 9 mmHg, MBG excretion increased (42.0 ± 7.6 vs. 10.0 ± 1.5 pmol/24 h, P < 0.01), whereas OLC peaked at day 1(25.0 ± 2.5 vs. 10.0 ± 2.0 pmol/24 h, P < 0.01) and remained elevated. Heart and kidney weights were increased in Salt and Iso+Salt. Aortic weights were increased in Iso and Iso+Salt. Thus a high NaCl intake stimulates MBG excretion, whereas isolation stress stimulates OLC. The combination of Salt and Iso is accompanied by marked stimulation of both SPL.
Sustained influence of the renal nerves to attenuate sodium retention in angiotensin hypertension
Authors: Lohmeier Thomas E. , Lohmeier Justin R. , Reckelhoff Jane F. , Hildebrandt Drew A.
Published: December 2017

Recent studies indicate that baroreflex suppression of renal sympathetic nerve activity is sustained for up to 5 days of ANG II infusion; however, steady-state conditions are not associated with ANG II hypertension of this short duration. Thus the major goal of this study was to determine whether neurally induced increments in renal excretory function during chronic intravenous infusion of ANG II are sustained under more chronic conditions when hypertension is stable and sodium balance is achieved. Experiments were conducted in five conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. ANG II was infused after control measurements for 10 days at a rate of 5 ng · kg−1· min−1. Twenty-four-hour control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 92 ± 4 mmHg and 0.99 ± 0.05, respectively. On days 8–10 of ANG II infusion, MAP was stable (+30 ± 3 mmHg) and sodium balance was achieved. Whereas equal amounts of sodium were excreted from the kidneys during the control period, throughout ANG II infusion there was a greater rate of sodium excretion from Inn vs. Den kidneys ( day 10 Den/Inn sodium = 0.56 ± 0.05), indicating chronic suppression of renal sympathetic nerve activity. The greater rate of sodium excretion in Inn vs. Den kidneys during renal sympathoinhibition also revealed a latent impairment in sodium excretion from Den kidneys. Although the Den/Inn for sodium and the major metabolites of nitric oxide (NO) decreased in parallel during ANG II hypertension, the Den/Inn for cGMP, a second messenger of NO, remained at control levels throughout this study. This disparity fails to support the notion that a deficiency in NO production and action in Den kidneys accounts for the impaired sodium excretion. Most importantly, these results support the contention that baroreflex suppression of renal sympathetic nerve activity is sustained during chronic ANG II hypertension, a response that may play an important role in attenuating the rise in arterial pressure.
Endothelin-1-induced vasoconstriction is inhibited during erection in rats
Authors: Mills T. M. , Pollock D. M. , Lewis R. W. , Branam H. S. , Wingard C. J.
Published: December 2017

Recent evidence indicates that endothelin-1 (ET-1) might be a principal vasoconstrictor in the penis. We report that ET-1 injection into the cavernous sinuses before erection sharply reduced the magnitude of subsequent erections. Corpus cavernosum pressure-to-mean arterial pressure ratios (CCP/MAP), with maximal ganglionic stimulation, were 0.62 ± 0.05 before ET-1 injection and 0.31 ± 0.05 after, indicating that ET-1 acted as a vasoconstrictor. When ET-1 was injected during a maximal neurally induced erection, the ability of ET-1 to attenuate subsequent erections was diminished (CCP/MAP 0.75 ± 0.02 before ET-1, 0.61 ± 0.03 after). At submaximal stimulation voltages, injection of ET-1 during erection also attenuated its vasoconstrictive effect. Similarly, when ET-1 was injected during erection induced by intracavernosal injection of the nitric oxide (NO) donor NOR-1, subsequent erections were not significantly suppressed (CCP/MAP 0.53 ± 0.04 before ET-1, 0.45 ± 0.04 after). These findings that ET-1-induced vasoconstriction is attenuated during erection are consistent with the hypothesis that NO mediates erection both by initiating pathways that cause smooth muscle relaxation and by inhibiting the vasoconstrictive actions of ET-1.
Parasite infection and caloric restriction induce physiological and morphological plasticity
Authors: Kristan Deborah M. , Hammond Kimberly A.
Published: December 2017

To investigate the effects of parasitism and caloric restriction on morphology (body composition, organ mass) and physiology (resting metabolism, intestinal glucose transport capacity), we gave laboratory mice intestinal parasites ( Heligmosomoides polygyrus, Nematoda), 30% caloric restriction, or both. Calorically restricted mice had smaller body mass, enhanced glucose transport capacity, and lower resting metabolism than ad libitum-fed mice. Parasitized mice maintained body mass, had diminished intestinal glucose transport capacity, and greater resting metabolism than unparasitized mice. Parasitized, calorically restricted mice had smaller organ masses than parasitized, ad libitum-fed mice and did not increase their glucose uptake rate as much as unparasitized, calorically restricted mice. There was a significant interaction between caloric restriction and parasite status for morphological variables but not for physiological variables. Knowing the types of phenotypic changes that occur with simultaneous parasitism and caloric restriction will provide insight into understanding human helminthiasis in food-restricted communities and also how wild animals cope with environments where parasitism and seasonal food restriction are common.
Differential role of adrenoceptors in control of plasma glucose and fatty acids in carp,Cyprinus carpio(L.)
Authors: Van Den Thillart Guido , Vianen Gerjanne , Ponce Maiza Campos , Lelieveld Harm , Nieveen Maaike , Van Raaij Marcel , Steffens Anton , Zaagsma Johan
Published: December 2017

Carp were cannulated in the dorsal aorta, and after 2 days of recovery they were infused with 1) norepinephrine, 2) yohimbine (α2-antagonist) plus norepinephrine, 3) clonidine (α2-agonist), and 4) isoproterenol (nonselective β-agonist). Norepinephrine lowered the plasma free fatty acid (FFA) level and raised the plasma glucose level for several hours. Norepinephrine in combination with the α2-antagonist yohimbine resulted in retardation of the FFA decrease, indicating the involvement of α2-adrenoceptors. Infusion with the partial α2-agonist clonidine had a smaller effect. Infusion with isoproterenol caused a marked increase of glucose levels, and unexpectedly a decline of plasma FFA levels, indicating a direct involvement of β-adrenoceptors. Combination of isoproterenol with either atenolol (β1-antagonist) or ICI-118,551 (β2-antagonist) showed that both β1- and β2-adrenoceptors were involved in the glucose release by isoproterenol. Remarkably, the decline of FFA levels was augmented in the presence of ICI-118,551, whereas with atenolol present plasma FFA levels were increased by isoproterenol. Thus it is concluded that in carp both β1- and β2-adrenoceptors mediate glucose release, whereas lipolysis is controlled by inhibitory β1-adrenoceptors and stimulatory β2-adrenoceptors, as well as by inhibitory α2-adrenoceptors.
Evidence that hemorrhagic hypotension is mediated by the ventrolateral periaqueductal gray region
Authors: Cavun Sinan , Millington William R.
Published: December 2017

Severe hemorrhage lowers arterial pressure by suppressing sympathetic activity. This study tested the hypothesis that the decompensatory phase of hemorrhage is mediated by the ventrolateral periaqueductal gray (vlPAG), a region importantly involved in the autonomic and behavioral responses to stress and trauma. Neuronal activity in the vlPAG was inhibited with either lidocaine or cobalt chloride 5 min before hemorrhage (2.5 ml/100 g body wt) was initiated in conscious, unrestrained rats. Bilateral injection of lidocaine (0.5 μl of a 2% or 1 μl of a 5% solution) into the caudal vlPAG delayed the onset and reduced the magnitude of the hypotension produced by hemorrhage significantly. In contrast, inactivation of the dorsolateral PAG with lidocaine was ineffective. Cobalt chloride (5 mM; 0.5 μl), which inhibits synaptic transmission but not axonal conductance, also attenuated hemorrhagic hypotension significantly. Microinjection of lidocaine or cobalt chloride into the vlPAG of normotensive, nonhemorrhaged rats did not influence cardiovascular function. These data indicate that the vlPAG plays an important role in the response to hemorrhage.
Effect of leptin on intestinal apolipoprotein AIV in response to lipid feeding
Authors: Doi Takashi , Liu Min , Seeley Randy J. , Woods Stephen C. , Tso Patrick
Published: December 2017

We determined apolipoprotein AIV (apo AIV) content in intestinal epithelial cells using immunohistochemistry when leptin was administered intravenously. Most of the apo AIV immunoreactivity in the untreated intestine was located in the villous cells as opposed to the crypt cells. Regional distribution of apo AIV immunostaining revealed low apo AIV content in the duodenum and high content in the jejunum that gradually decreases caudally toward the ileum. Intraduodenal infusion of lipid (4 h) significantly increased apo AIV immunoreactivity in the jejunum and ileum. Simultaneous intravenous leptin infusion plus duodenal lipid infusion markedly suppressed apo AIV immunoreactivity. Duodenal lipid infusion increased plasma apo AIV significantly (measured by ELISA), whereas simultaneous leptin infusion attenuated the increase. These findings suggest that leptin may regulate circulating apo AIV by suppressing apo AIV synthesis in the small intestine.
Restraint increases prolactin and REM sleep in C57BL/6J mice but not in BALB/cJ mice
Authors: Meerlo Peter , Easton Amy , Bergmann Bernard M. , Turek Fred W.
Published: December 2017

Sleep is generally considered to be a recovery from prior wakefulness. The architecture of sleep not only depends on the duration of wakefulness but also on its quality in terms of specific experiences. In the present experiment, we studied the effects of restraint stress on sleep architecture and sleep electroencephalography (EEG) in different strains of mice (C57BL/6J and BALB/cJ). One objective was to determine if the rapid eye movement (REM) sleep-promoting effects of restraint stress previously reported for rats would also occur in mice. In addition, we examined whether the effects of restraint stress on sleep are different from effects of social defeat stress, which was found to have a non-REM (NREM) sleep-promoting effect. We further measured corticosterone and prolactin levels as possible mediators of restraint stress-induced changes in sleep. Adult male C57BL/6J and BALB/cJ mice were subjected to 1 h of restraint stress in the middle of the light phase. To control for possible effects of sleep loss per se, the animals were also kept awake for 1 h by gentle handling. Restraint stress resulted in a mild increase in NREM sleep compared with baseline, but, overall, this effect was not significantly different from sleep deprivation by gentle handling. In contrast, restraint stress caused a significant increase in REM sleep compared with handling in the C57BL/6J mice but not in BALB/cJ mice. Corticosterone levels were significantly and similarly elevated after restraint in both strains, but prolactin was increased only in the C57BL/6J mice. In conclusion, this study shows that the restraint stress-induced increase in REM sleep in mice is strongly strain dependent. The concomitant increases in prolactin and REM sleep in the C57BL/6J mice, but not in BALB/cJ mice, suggest prolactin may be involved in the mechanism underlying restraint stress-induced REM sleep. Furthermore, this study confirms that different stressors differentially affect NREM and REM sleep. Whereas restraint stress promotes REM sleep in C57BL/6J mice, we previously found that in the same strain, social defeat stress promotes NREM sleep. As such, studying the consequences of specific stressful stimuli may be an important tool to unravel both the mechanism and function of different sleep stages.
Activation of the kallikrein-kinin system by cardiopulmonary bypass in humans
Authors: Campbell Duncan J. , Dixon Barry , Kladis Athena , Kemme Michael , Santamaria John D.
Published: December 2017

We used cardiopulmonary bypass (CPB) as a model of activation of the contact system and investigated the involvement of the plasma and tissue kallikrein-kinin systems (KKS) in this process. Circulating levels of bradykinin and kallidin and their metabolites, plasma and tissue kallikrein, low and high molecular weight kininogen, and kallistatin were measured before, during, and 1, 4, and 10 h after CPB in subjects undergoing cardiac surgery. Bradykinin peptide levels increased 10- to 20-fold during the first 10 min, returned toward basal levels by 70 min of CPB, and remained 1.2- to 2.5-fold elevated after CPB. Kallidin peptide levels showed little change during CPB, but they were elevated 1.7- to 5.2-fold after CPB. There were reductions of 80 and 60% in plasma and tissue kallikrein levels, respectively, during the first minute of CPB. Kininogen and kallistatin levels were unchanged. Angiotensin-converting enzyme inhibition did not amplify the increase in bradykinin levels during CPB. Aprotinin administration prevented activation of the KKS. The changes in circulating kinin and kallikrein levels indicate activation of both the plasma and tissue KKS during activation of the contact system by CPB.
Impaired renal D1-like and D2-like dopamine receptor interaction in the spontaneously hypertensive rat
Authors: Ladines Cecilia A. , Zeng Chunyu , Asico Laureano D. , Sun Xiaoguang , Pocchiari Felice , Semeraro Claudio , Pisegna Joseph , Wank Stephen , Yamaguchi Ikuyo , Eisner Gilbert M. , Jose Pedro A.
Published: December 2017

D1-like (D1, D5) and D2-like (D2, D3, D4) dopamine receptors interact in the kidney to produce a natriuresis and a diuresis. Disruption of D1or D3receptors in mice results in hypertension that is caused, in part, by a decreased ability to excrete an acute saline load. We studied D1-like and D2-like receptor interaction in anesthetized spontaneously hypertensive rats (SHR) by the intrarenal infusion of Z-1046 (a novel dopamine receptor agonist with rank order potency of D3≥D4>D2>D5>D1). Z-1046 increased glomerular filtration rate (GFR), urine flow, and sodium excretion in normotensive Wistar-Kyoto rats but not in SHRs. The lack of responsiveness to Z-1046 in SHRs was not an epiphenomenon, because intrarenal cholecystokinin infusion increased GFR, urine flow, and sodium excretion to a similar extent in the two rat strains. We conclude that renal D1-like and D2-like receptor interaction is impaired in SHRs. The impaired D1-like and D2-like receptor interaction in SHRs is not caused by alterations in the coding sequence of the D3receptor, the D2-like receptor expressed in rat renal tubules that has been shown to be involved in sodium transport. Because the diuretic and natriuretic effects of D1-like receptors are, in part, caused by an interaction with D2-like receptors, it is possible that the decreased Z-1046 action in SHRs is secondary to the renal D1-like receptor dysfunction in this rat strain.
Regulation of fetal cardiac and hepatic β-adrenoceptors and adenylyl cyclase signaling: terbutaline effects
Authors: Auman J. T. , Seidler F. J. , Slotkin T. A.
Published: December 2017

Terbutaline (Ter), a β2-adrenergic agonist used in preterm labor, stimulates fetal β-adrenoceptors (β-ARs). We administered Ter to pregnant rats on gestational days 17–20 and examined β-ARs and adenylyl cyclase (AC) signaling in heart and liver. Ter produced less downregulation of cardiac β-ARs than in adults, despite a higher proportion of the β2-subtype, and failed to elicit desensitization of the receptor-mediated AC response. AC stimulants acting at different points indicated an offsetting of homologous desensitization at the level of the β-AR by heterologous sensitization at the level of AC: induction of total AC catalytic activity and a shift in the catalytic profile or AC isoform. In fetal liver, Ter produced downregulation of β-ARs, in keeping with the predominance of the β2-subtype; hepatic receptor downregulation was equivalent in fetus and adult. Nevertheless, there was still no desensitization of β-AR-mediated AC responses and again AC was induced. Our results indicate that, unlike in the adult, fetal β-AR signaling is not desensitized by β-agonists and, in fact, displays heterologous sensitization, thus sustaining responses during parturition. At the same time, the inability to desensitize β-AR AC responses may lead to disruption of cardiac, hepatic, or neural cell development as a consequence of tocolytic therapy with β-agonists.
Comparison of the exercise pressor reflex between forelimb and hindlimb muscles in cats
Authors: Hayashi Naoyuki , Hayes Shawn G. , Kaufman Marc P.
Published: December 2017

In thirteen cats anesthetized with α-chloralose, we compared the cardiovascular and ventilatory responses to both static contraction and tendon stretch of a hindlimb muscle group, the triceps surae, with those to contraction and stretch of a forelimb muscle group, the triceps brachii. Static contraction and stretch of both muscle groups increased mean arterial pressure and heart rate, and the responses were directly proportional to the developed tension. The cardiovascular increases, however, were significantly greater ( P < 0.05) when the triceps brachii muscles were contracted or stretched than when the triceps surae muscles were contracted or stretched, even when the tension developed by either maneuver was corrected for muscle weight. Likewise, the ventilatory increases were greater when the triceps brachii muscles were stretched than when the triceps surae muscles were stretched. Contraction of either muscle group did not increase ventilation. Our results suggest that in the anesthetized cat the cardiovascular responses to both static contraction and tendon stretch are greater when arising from forelimb muscles than from hindlimb muscles.
Influence of oral and gastric NaCl preloads on NaCl intake and gastric emptying of sodium-deficient rats
Authors: Tordoff Michael G. , McCaughey Stuart A.
Published: December 2017

Evidence is mixed as to whether oral metering contributes to the satiation of NaCl intake. To examine this in detail, we measured NaCl intake of sodium-deficient rats given preloads of NaCl that were sham ingested, normally ingested, or intubated into the stomach. Intake of 500 mM NaCl was reduced by prior ingestion, but not by sham ingestion, of an NaCl preload. NaCl intubation reduced NaCl intake if the test began 15 min, but not 60 min, after the preload. Gastric emptying of NaCl was initially more rapid after intubated than after ingested NaCl. Plasma aldosterone concentrations dropped more rapidly after ingested than after intubated NaCl and also dropped after sham ingestion of NaCl, raising the possibility of a cephalic-phase influence on aldosterone levels. These findings suggest that oral factors do not directly control the amount of NaCl consumed by sodium-deprived rats. Differences between the physiological effects of voluntary ingestion and intubation may be responsible for the results of several early studies purported as evidence for oral metering of sodium consumption.
Plasma hormone levels and central c-Fos expression in ferrets after systemic administration of cholecystokinin
Authors: Billig I. , Yates B. J. , Rinaman L.
Published: December 2017

Posterior pituitary hormone secretion and central neural expression of the immediate-early gene product c-Fos was examined in adult ferrets after intravenous administration of CCK octapeptide. Pharmacological doses of CCK (1, 5, 10, or 50 μg/kg) did not induce emesis, but elicited behavioral signs of nausea and dose-related increases in plasma vasopressin (AVP) levels without significant increases in plasma oxytocin (OT) levels. CCK activated neuronal c-Fos expression in several brain stem viscerosensory regions, including a dose-related activation of neurons in the dorsal vagal complex (DVC). Activated brain stem neurons included catecholaminergic and glucagon-like peptide-1-positive cells in the DVC and ventrolateral medulla. In the forebrain, activated neurons were prevalent in the paraventricular and supraoptic nuclei of the hypothalamus and also were observed in the central nucleus of the amygdala and bed nucleus of the stria terminalis. Activated hypothalamic neurons included cells that were immunoreactive for AVP, OT, and corticotropin-releasing factor. Comparable patterns of brain stem and forebrain c-Fos activation were observed in ferrets after intraperitoneal injection of lithium chloride (LiCl; 86 mg/kg), a classic emetic agent. However, LiCl activated more neurons in the area postrema and fewer neurons in the nucleus of the solitary tract compared with CCK. Together with results from previous studies in rodents, our findings support the view that nauseogenic treatments activate similar central neural circuits in emetic and nonemetic species, despite differences in treatment-induced emesis and pituitary hormone secretion.
Glutamate and GABA mediate suprachiasmatic nucleus inputs to spinal-projecting paraventricular neurons
Authors: Cui Lu-Ning , Coderre Elaine , Renaud Leo P.
Published: December 2017

We used patch-clamp recordings in slice preparations from Sprague-Dawley rats to evaluate responses of 20 spinal-projecting neurons in the dorsal paraventricular nucleus (PVN) to electrical stimulation in suprachiasmatic nucleus (SCN). Neurons containing a retrograde label transported from the thoracic (T1-T4) intermediolateral column displayed three intrinsic properties that collectively allowed distinction from neighboring parvocellular or magnocellular cells: a low-input resistance, a hyperpolarization-activated time-dependent inward rectification, and a low-threshold calcium conductance. Twelve of fifteen cells tested responded to electrical stimulation in SCN. All of 10 cells tested in media containing 2,3,-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium (5 μM) andd(−)-2-amino-5-phosphonopentanoic acid (20 μM) responded with constant latency (11.4 ± 0.7 ms) inhibitory postsynaptic potentials, able to follow 20- to 50-Hz stimulation and blockable with bicuculline (20 μM). By contrast, all eight cells tested in the presence of bicuculline demonstrated constant latency (9.8 ± 0.6 ms) excitatory postsynaptic potentials that followed at 20–50 Hz and featured both non- N-methyl-d-aspartate (NMDA) and NMDA receptor-mediated components. We conclude that both GABAergic and glutamatergic neurons in SCN project directly to spinal-projecting neurons in the dorsal PVN.
Hyperglycemia compensates for diet-induced insulin resistance in liver and skeletal muscle of rats
Authors: Commerford S. Renee , Bizeau Michael E. , McRae Heather , Jampolis Ami , Thresher Jeffrey S. , Pagliassotti Michael J.
Published: December 2017

High-fat and high-sucrose diets increase the contribution of gluconeogenesis to glucose appearance (glc Ra) under basal conditions. They also reduce insulin suppression of glc Raand insulin-stimulated muscle glycogen synthesis under euglycemic, hyperinsulinemic conditions. The purpose of the present study was to determine whether these impairments influence liver and muscle glycogen synthesis under hyperglycemic, hyperinsulinemic conditions. Male rats were fed a high-sucrose, high-fat, or low-fat, starch control diet for either 1 ( n = 5–7/group) or 5 wk ( n = 5–6/group). Studies involved two 90-min periods. During the first, a basal period (BP), [6-3H]glucose was infused. In the second, a hyperglycemic period (HP), [6-3H]glucose, [6-14C]glucose, and unlabeled glucose were infused. Plasma glucose (BP: 111.2 ± 1.5 mg/dl; HP: 172.3 ± 1.5 mg/dl), insulin (BP: 2.5 ± 0.2 ng/ml; HP: 4.9 ± 0.3 ng/ml), and glucagon (BP: 81.8 ± 1.6 ng/l; HP: 74.0 ± 1.3 ng/l) concentrations were not significantly different among diet groups or with respect to time on diet. There were no significant differences among groups in the glucose infusion rate (mg · kg−1· min−1) necessary to maintain arterial glucose concentrations at ∼170 mg/dl (pooled average: 6.4 ± 0.8 at 1 wk; 6.4 ± 0.7 at 5 wk), percent suppression of glc Ra(44.4 ± 7.8% at 1 wk; 63.2 ± 4.3% at 5 wk), tracer-estimated net liver glycogen synthesis (7.8 ± 1.3 μg · g liver−1· min−1at 1 wk; 10.5 ± 2.2 μg · g liver−1· min−1at 5 wk), indirect pathway glycogen synthesis (3.7 ± 0.9 μg · g liver−1· min−1at 1 wk; 3.4 ± 0.9 μg · g liver−1· min−1at 5 wk), or tracer-estimated net muscle glycogenesis (1.0 ± 0.3 μg · g muscle−1· min−1at 1 wk; 1.6 ± 0.3 μg · g muscle−1· min−1at 5 wk). These data suggest that hyperglycemia compensates for diet-induced insulin resistance in both liver and skeletal muscle.
Role of neuronal nitric oxide synthase in mediating renal hemodynamic changes during pregnancy
Authors: Abram S. R. , Alexander B. T. , Bennett W. A. , Granger J. P.
Published: December 2017

Renal plasma flow (RPF) and glomerular filtration rate (GFR) are markedly increased during pregnancy. We recently reported that the renal hemodynamic changes observed during pregnancy in rats are associated with enhanced renal protein expression of neuronal nitric oxide synthase (nNOS). The purpose of this study was to determine the role of nNOS in mediating renal hemodynamic changes observed during pregnancy. To achieve this goal, we examined the effects of the nNOS inhibitor 7-nitroindazole (7-NI) on kidney function in normal conscious, chronically instrumented virgin ( n = 6) and pregnant rats ( n = 9) at day 16 of gestation. Infusion of 7-NI had no effect on RPF (4.7 ± 0.7 vs. 4.8 ± 0.9 ml/min), GFR (2.2 ± 0.2 vs. 2.5 ± 0.4 ml/min), or mean arterial pressure (MAP; 127 ± 7 vs. 129 ± 10 mmHg) in virgin rats. In contrast, 7-NI infused into pregnant rats decreased RPF (8.9 ± 1.6 vs. 6.5 ± 1.4 ml/min) and GFR (4.4 ± 0.7 vs. 3.3 ± 0.7 ml/min) while having no effect on MAP (123 ± 4 vs. 123 ± 3 mmHg). In summary, inhibition of nNOS in pregnant rats at midgestation results in significant decreases in RPF and GFR. nNOS inhibition in virgin rats had no effect on renal hemodynamics. These data suggest that nNOS may play a role in mediating the renal hemodynamic changes that occur during pregnancy.