bluuebunny/crossref_metadata_2025 huggingface dataset:
Attenuation of glucose metabolic changes resulting from TNF-alpha administration by adrenergic blockade
Authors: Bagby G. J. , Lang C. H. , Skrepnik N. , Spitzer J. J.
Published: December 2017

Administration of tumor necrosis factor (TNF-alpha) increases whole body glucose kinetics and stimulates in vivo glucose uptake by several tissues. Because circulating catecholamines are also increased after TNF-alpha administration, the present study was conducted to examine the potential role of the adrenergic system in eliciting these changes. Rats given 150 micrograms TNF-alpha/kg by intravenous infusion over a 30-min period exhibited an increased rate of glucose appearance (glucose Ra). Combined alpha- and beta-adrenergic blockade (phentolamine and propranolol infusion) prevented the TNF-alpha-induced increase in glucose Ra without influencing plasma glucagon or corticosterone levels. TNF-alpha infusion also increased in vivo glucose utilization (Rg), measured with 2-deoxy-[14C]glucose, in spleen (86%), liver (80%), skin (47%), ileum (71%), lung (53%), and heart (112%). Adrenergic blockade prevented the tissue Rg increase in the spleen, liver, and skin; partially reduced it in the ileum; but did not abrogate it in the lung or heart. The effect of blockade was primarily due to inhibition of the TNF-alpha-induced increase in hepatic glucose output. Whereas the adrenergic system plays a major role on the effect of TNF-alpha on whole body glucose production, its importance in directly mediating TNF-alpha's effect on tissue glucose uptake is minimal.
Hypothalamic excitatory amino acid receptors mediate stress-induced tachycardia in rats
Authors: Soltis R. P. , DiMicco J. A.
Published: December 2017

The role of hypothalamic excitatory amino acid (EAA) receptors in mediating the cardiovascular response to stress was examined using conscious chronically instrumented rats. Microinjection of the EAA agonists N-methyl-D-aspartic acid (NMDA; 1-10 pmol), alpha-amino-3-hydroxy-5-methyl-4-isooxazolepropionic acid (AMPA; 0.3-3.0 pmol), or kainic acid (0.1-1.0 pmol) into the dorsomedial hypothalamus (DMH) elicited dose-related increases in heart rate and modest elevations in arterial pressure. Local microinjection of the NMDA antagonist 2-amino-5-phosphonopentanoic acid (AP5; 100 pmol) selectively blocked NMDA-induced cardiovascular changes, whereas the non-NMDA EAA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 pmol) selectively blocked the responses to AMPA and kainic acid. In the stress trials, microinjection of the nonselective EAA antagonist kynurenic acid (1-10 nmol) into the DMH blocked air stress-induced tachycardia in a dose-related manner. Similar injection of kynurenic acid at sites lateral or posterior to the DMH or injection of xanthurenic acid (a structural analogue of kynurenic acid with no antagonistic properties at EAA receptors) into the DMH failed to influence air stress-induced cardiovascular changes. Injection of either AP5 or CNQX into the DMH at doses shown to be selective for their respective EAA receptor subtypes also attenuated air stress-induced tachycardia. Thus activity at EAA receptors in the DMH appears to be necessary for the generation of stress-induced changes in heart rate.
Energetic cost of locomotion in the tammar wallaby
Authors: Baudinette R. V. , Snyder G. K. , Frappell P. B.
Published: December 2017

Rates of oxygen consumption and blood lactate levels were measured in tammar wallabies (Macropus eugenii) trained to hop on a treadmill. In addition, the work required to overcome wind resistance during forward locomotion was measured in a wind tunnel. Up to approximately 2.0 m/s, rates of oxygen consumption increased linearly with speed and were not significantly different from rates of oxygen consumption for a quadruped of similar body mass. Between 2.0 and 9.4 m/s, rates of oxygen consumption were independent of hopping speed, and between 3.9 and 7.9 m/s, the range over which samples were obtained, blood lactate levels were low (0.83 +/- 0.13 mmol.min-1.kg-1) and did not increase with hopping speed. The work necessary to overcome drag increased exponentially with speed but increased the energy cost of locomotion by only 10% at the average speed attained by our fast hoppers. Thus, during hopping, the energy cost of locomotion is effectively independent of speed. At rates of travel observed in the field, the estimated energy cost of transport in large macropods is less than one-third the cost for a quadruped of equivalent body mass. The energetic savings associated with this unique form of locomotion may have been an important physiological adaptation, enabling large macropods to efficiently cover the distances necessary to forage in the semiarid landscapes of Australia.
Relationship between vasopressin and renal concentrating ability in aging rats
Authors: Geelen G. , Corman B.
Published: December 2017

The relationship between arginine vasopressin (AVP) secretion and the age-related change in renal concentrating ability was studied in 10-, 20-, and 30-mo-old conscious rats. In control condition, urine osmolality (Uosmol) was 2,358 +/- 99, 1,919 +/- 87, and 1,135 +/- 173 mosmol/kgH2O (mean +/- SE) and the corresponding plasma AVP concentration 3.1 +/- 1.2, 2.8 +/- 0.7, and 3.3 +/- 0.7 pg/ml at 10, 20, and 30 mo. Urinary AVP excretion and AVP content in the hypothalamus were comparable in the 3 age groups, while the basal AVP pituitary content was significantly higher at 10 than at 20 or 30 mo. Three days of dehydration induced 1) a similar increase in plasma concentration and urinary excretion of AVP in the 3 groups, even though the maximal Uosmol reached by the oldest animals was significantly reduced (3,988 +/- 218, 3,652 +/- 273, and 2,826 +/- 197 mosmol/kgH2O at 10, 20, and 30 mo, respectively) and 2) a similar AVP depletion of the pituitary at 10, 20, and 30 mo and an increase of the AVP content in the hypothalamus at 10 mo but not at 20 and 30 mo. These results suggest that the decrease in renal concentrating ability reported in aging rats is not due to an inappropriate secretion of AVP along the hypothalamo-neurohypophysial axis but is rather related to an impaired responsiveness of the kidney to the antidiuretic hormone.
Expiratory bulbospinal neurons of dogs. I. Control of discharge patterns by pulmonary stretch receptors
Authors: Bajic J. , Zuperku E. J. , Tonkovic-Capin M. , Hopp F. A.
Published: December 2017

To better understand expiratory bulbospinal (EBS) neuronal processing of afferent patterns from slowly adapting pulmonary stretch receptors (PSRs), the responses of these caudal medullary neurons to various inflation patterns were analyzed in thiopental sodium-anesthetized paralyzed dogs. Normocapnic ventilation was obtained from lung inflations delivered during the neural inspiratory phase of control respiratory cycles by a solenoid ventilator triggered by the onset of phrenic nerve activity. Test inflation patterns, delivered during the neural expiratory (E) phase of specific cycles, were separated by 6-10 control cycles and consisted of slow augmenting and decrementing ramps and steps. Transpulmonary pressure (Pt) was used as an index of PSR activity, and the discharge patterns of single EBS neurons were quantified using cycle-triggered histograms. Based on the time course of the discharge pattern during no-inflation cycles, two types of neurons were identified. Type D, the most common, exhibited a decrementing-like pattern, while type A exhibited an augmenting-plateau pattern. Plots of discharge frequency vs. Pt for type D neurons consisted of a linear excitatory phase (1 less than Pt less than 4.6 mmHg) and a linear inhibitory phase (4.6 less than Pt less than 12 mmHg). Type A neurons exhibited only a linear inhibitory phase for 3.3 less than Pt less than 12 mmHg. Because the responses to step inflations (4 s duration) exhibited only a small amount of time dependency, and the activation Pt of PSRs, but not of the other pulmonary receptors with vagal fibers, is in the proper range, it appears that PSRs may mediate both excitatory and inhibitory components of the neuronal response. These data suggest that discharge patterns of the caudal EBS neurons in dogs are highly dependent on the time course of Pt in a predictable manner, and implicate the importance of instantaneous lung volume in the control of the E musculature and the optimization of the breathing pattern.
Individual, but not simultaneous, glucagon and cholecystokinin infusions inhibit feeding in men
Authors: Geary N. , Kissileff H. R. , Pi-Sunyer F. X. , Hinton V.
Published: December 2017

Pancreatic glucagon and cholecystokinin octapeptide (CCK-8) were intravenously infused (1 ml/min for 10 min) alone or in combination beginning 15 min after normal-weight men had eaten a 500-ml tomato soup preload and 5 min before they were served a lunch of macaroni and beef with tomato sauce. Infusion of approximately 3 ng.kg-1.min-1 glucagon or approximately 2 ng.kg-1.min-1 CCK-8 each reduced test meal size. However, simultaneous infusion of these peptide doses reduced meal size less than the sum of the peptides' individual effects. Infusions of approximately 1.5 ng.kg-1.min-1 glucagon or approximately 1 ng.kg-1.min-1 CCK-8 had neither individual nor interactive effects on meal size. Psychophysical ratings failed to detect nonspecific side effects after any of the infusions. That exogenous glucagon and CCK-8 each reduced meal size without side effects suggests that these peptides may participate in the physiological control of human appetite; that their simultaneous infusion resulted in an infra-additive reduction in meal size suggests that they can interact antagonistically.
Pituitary-adrenal responses to head-up tilt in humans: effect of H1- and H2-receptor blockade
Authors: Matzen S. , Secher N. H. , Knigge U. , Bach F. W. , Warberg J.
Published: December 2017

Effects of the histamine H1- or H2-receptor antagonists mepyramine (Mep) and cimetidine (Cim) on neuroendocrine and cardiovascular responses to 50 degrees head-up tilt were evaluated in seven human males. Central hypovolemia was characterized by two phases. The first is a normotensive phase with increases in heart rate (HR), total peripheral resistance (TPR), and decrease in cardiac output. Plasma adrenocorticotropic hormone, beta-endorphin, cortisol, catecholamines, and renin activity increased moderately. Normotension lasted 39 +/- 7 min during infusion of saline but was reduced by Mep [18 +/- 3 min, F(2,12) = 9.60, P less than 0.01] and was unaffected by Cim (44 +/- 4 min). The second is a hypotensive phase associated with presyncopal symptoms (hypovolemic shock) and decreases in HR and TPR and a further increase in pituitary-adrenal and sympathoadrenal activity. Decreases in mean arterial pressure and TPR were augmented by Mep, which inhibited release of norepinephrine. Cim inhibited epinephrine release without affecting the development of hypovolemic shock. It is concluded that histaminergic mechanisms are involved in activation of the sympathoadrenal system but not in the pituitary-adrenal axis during central hypovolemia in humans.
Diverse effects of calcium channel blockers on skeletal muscle glucose transport
Authors: Cartee G. D. , Briggs-Tung C. , Holloszy J. O.
Published: December 2017

Verapamil, a calcium channel blocker, inhibited the insulin-stimulated glucose transport rate in isolated rat epitrochlearis muscle in a dose-dependent manner (1-200 microM) without affecting basal glucose transport rate. Verapamil's inhibition was rapid in onset and disappearance; changes in glucose transport rate were detectable when verapamil was added to or removed from the incubation medium 15 min prior to measurement of glucose transport. Verapamil also inhibited the stimulation of muscle glucose transport caused by hypoxia, indicating that the effect was not limited to insulin action. Although the optical isomers of verapamil vary considerably in their potency as Ca2+ channel blockers, they were equally effective inhibitors of insulin-stimulated glucose transport rate. Nifedipine (10-200 microM), a more potent blocker of skeletal muscle Ca2+ channels than verapamil, was less effective as an inhibitor of insulin-stimulated glucose transport. Furthermore, nifedipine (10 microM) did not inhibit hypoxia-stimulated glucose transport. Diltiazem (200 microM), another Ca2+ channel blocker, did not reduce insulin-stimulated glucose transport.
Ion transport by the isolated mantle epithelium of the freshwater clam, Unio complanatus
Authors: Hudson R. L.
Published: December 2017

Transepithelial ion transport was studied in three types of shell-facing mantle epithelia of the freshwater clam, Unio complanatus. These were 1) the epithelium isolated from near the margin of the shell; 2) the epithelium from the central region of a “normal” shell; and 3) the epithelium from the central region that was regenerating a damaged shell. Marginal and “shell-regenerating” epithelia produced a small (less than 5 mV) transepithelial voltage that was independent of PCO2 (0-4%). In the presence of 4% PCO2, the “normal” central epithelium produced a significantly larger transepithelial voltage (-8.5 +/- 0.99 mV), that, in addition, could be stimulated (-30.5 +/- 2.18 mV) by permeable analogues of adenosine 3',5'-cyclic monophosphate (cAMP) [e.g., 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate]. Voltage clamping the transepithelial voltage to zero resulted in a short-circuit current (Isc) that was consistent with positive charge moving from the hemolymph toward the shell. The measurements of transepithelial fluxes of 45Ca, 22Na, 42K, and 36Cl revealed that none of these ions, alone or in combination, could account for the stimulated Isc in “normal” mantle. In addition, similar measurements in marginal and “shell-regenerating” epithelia did not detect any significant net transepithelial flux of any of these ions. Acid extrusion at the shell-facing membrane and bicarbonate extrusion at the hemolymph-facing membrane were identified in “normal” central epithelium, but could not be found in marginal or “shell-regenerating” epithelia. These fluxes are equivalent to the cAMP-stimulated Isc in “normal” central epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Catecholamine depletion of the diagonal band reduces baroreflex inhibition of supraoptic neurons
Authors: Cunningham J. T. , Nissen R. , Renaud L. P.
Published: December 2017

In the rat, neurons in the diagonal band of Broca (DBB) participate in baroreceptor-induced depression of spontaneous activity of vasopressin neurons in the supraoptic nucleus (SON). The present study examined the role of the catecholaminergic innervation of the DBB in this response. Male rats were anesthetized with pentobarbital (50 mg/kg ip) and stereotaxically injected in the DBB with either vehicle (2 microliters), 6-hydroxydopamine (6-OHDA; 4 micrograms/2 microliters), or 6-OHDA preceded 20 min earlier by desimipramine (25 mg/kg ip), a norepinephrine uptake inhibitor. Two weeks later, the rats were reanesthetized and a transpharyngeal approach was used for extracellular recording from SON neurons. In vehicle-injected controls, baroreceptor stimulation produced by brief increases in blood pressure from metaraminol injections (10 micrograms/10 microliters iv) transiently arrested the spontaneous activity of 24 of 24 phasically active neurons tested. Sixty-three percent of the vasopressin neurons were not affected by comparable increases in blood pressure in 6-OHDA-treated rats, and the norepinephrine content of the DBB was significantly reduced. In experiments with desimipramine-pretreated rats, 92% of the vasopressin neurons were silenced by increases in blood pressure while the norepinephrine content of the DBB was not affected. Thus the noradrenergic innervation of DBB appears to participate in the baroreceptor sensitivity of SON vasopressinergic neurons.
Vertebrate intestine apical membrane mechanisms of organic nutrient transport
Authors: Stevens B. R.
Published: December 2017

This paper presents the current understanding of comparative vertebrate intestine basic mechanisms of brush-border membrane transport. Animals control the uptake of monosaccharides and amino acids at three levels: 1) mucosal hyperplasia increases uptake nonselectively, 2) individual enterocytes increase the transport capacity of specific transporter systems, and 3) the transporters themselves are modulated by solute and ion electrochemical gradients. In light of the current literature, This paper summarizes the kinetics, thermodynamics, and the physical arrangement of one mode of transport, the prototype Na(+)-solute cotransporter. The model presented is experimentally consistent with “preferred random” kinetics, with Na+ binding preferentially before solute at the extracellular face. In the case of glucose, the cotransporter system may be physically arranged in the membrane as a tetramer comprising 73,000 Da subunits. All vertebrates may have evolved with a similar mechanism, with particular variations reflecting selected arrangements from a pool of polypeptide sequence blocks. The same fundamental transport mechanisms may be observed in the intestines of animals ranging from lower vertebrates through humans.
Tests of the adaptive modulation hypothesis for dietary control of intestinal nutrient transport
Authors: Karasov W. H.
Published: December 2017

According to the adaptive modulation hypothesis, an intestinal transporter should be repressed when its biosynthetic and other costs (of maintenance) exceed the benefits it provides. This leads to two contrasting predictions: transport of a sugar or amino acid worth calories should tend to be increased by its substrate, and transport of a vitamin should be modulated downwards by its substrate and upmodulated in deficiency. In a test of the first prediction, omnivorous desert iguanas eating alfalfa pellets (a high-carbohydrate diet) were compared with desert iguanas eating mealworms (a low-carbohydrate, higher-protein diet). In accord with the prediction, intact intestinal sleeves from the former group had higher rates of carrier-mediated D-glucose uptake/centimeter across the brush border than sleeves from the latter group. But in contrast to the first prediction, mealworm eaters had lower (not higher) proline uptake rates, and the ratio of glucose/proline uptake in the two groups did not differ. I review similar tests in 12 other species and show that overall the hypothesis has been quite robust with regard to the first prediction. Cases in which the hypothesis is rejected may reflect complications associated with changes in other dietary factors or phylogenetic constraints. In a test of the second prediction, uptake of the water-soluble vitamin choline was not increased in choline-deficient chicks, nor was it decreased in adults that have no dietary requirement for choline. I review similar tests for four other vitamins and five essential minerals. Dietary control of transport of the minerals and two of the vitamins seems to be in accord with the hypothesis. But transport rate for three vitamins (choline, pantothenic acid, ascorbic acid) seems not to be increased in deficiency. The best explanation seems to be that vitamin transport is modulated only if it is primarily by a carrier-mediated pathway.
Muscle, joint, and tendon contributions to the torque profile of frog hip joint
Authors: Lieber R. L. , Shoemaker S. D.
Published: December 2017

The relative contributions of muscle force, moment arm, and tendon compliance were determined as a function of joint angle in the frog semitendinosus-hip joint system. Muscle, joint, and tendon properties were individually measured and then combined to predict the torque generated at the hip joint as a function of joint angle (i.e., the hip torque profile). Predicted torques were then compared to experimentally measured torques using a stepwise regression model to quantify the relative importance of muscle, joint, and tendon contributions to the hip torque profile. Variation in moment arm accounted for 74% of the variability observed in the hip torque profile, while addition of the muscle's intrinsic sarcomere length-tension property accounted for an additional 19% of the torque profile variability. Tendon compliance, which permitted a small amount of sarcomere shortening, accounted for only about 4% of the torque profile variability. We conclude that in this muscle-joint system, the relative fiber length-to-moment arm ratio is the major determinant of the shape of the isometric joint profile. The fiber length-to-moment arm ratio in other mammalian systems is also discussed.
Digital image analysis of shark gills: modeling of oxygen transfer in the domain of time
Authors: Bhargava V. , Lai N. C. , Graham J. B. , Hempleman S. C. , Shabetai R.
Published: December 2017

Digital radiographic imaging of blood circulation through leopard shark gills establishes a secondary lamellar transit time of 6.5 s. This duration, combined with estimates of cardiac output and hemoglobin-oxygen affinity, permits novel modeling of gill oxygen transfer in the time domain. The temporal model allows assessment of factors contributing to previously noted discrepancies between physiological and morphometric branchial oxygen conductance estimates. Lamellar transit time for shark blood is 20 times greater than human alveolar transit time, and thus correlates with a slower rate of hemoglobin-oxygen binding and a greater diffusion distance.
Aging alters feedback effects of the activity-rest cycle on the circadian clock
Authors: Van Reeth O. , Zhang Y. , Zee P. C. , Turek F. W.
Published: December 2017

Two different stimuli (i.e., benzodiazepines and dark pulses) inducing phase shifts in the circadian clock of young hamsters through changes in the level of activity do not induce phase shifts in old hamsters, despite the fact that these stimuli induce a similar acute change in locomotor activity in young and old animals. In contrast, old hamsters remain sensitive to the phase-shifting effects of stimuli clearly not associated with any change in locomotor activity (i.e., protein synthesis inhibitors or light). Thus the circadian system of old animals becomes selectively unresponsive to synchronizing signals mediated by the activity-rest state of the animals. Previous age-related changes in circadian rhythmicity that have been observed in mammals, including humans, may be related to a weakened coupling between the activity-rest cycle and the circadian clock.
Role of intracellular calcium in renal proximal tubule cell volume regulation
Authors: Terreros D. A. , Kanli H.
Published: December 2017

Osmoregulatory Ca2+ signaling in hypotonic solutions was studied with videometric techniques in 158 proximal renal tubules isolated from the teleost Carassius auratus. Absence of extracellular Ca2+, hypoxia (23 mmHg), or NaCN (3 mM) did not alter regulatory volume decreases (RVD). Nevertheless, decrements of intracellular Ca2+ via the A23187 ionophore or after intracellular Ca2+ chelation with indo-1/AM (5 microM) inhibited RVD. In tubules depleted of Ca2+, RVD could only be fully elicited when intracellular Ca2+ pulses were given within 1 min after hypotonic stimulation. While inhibition of Ca2+ release from the endoplasmic reticulum (ER) with 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8, 50 microM) blunted RVD, some of its effects could be reversed with the anion carrier tributyltin (1 microM). Dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP, 0.5 and 1.0 mM) and forskolin (0.25 mM) also impeded RVD; however, their effects could be partially reversed with the K+ ionophore gramicidin (0.5 microM). In conclusion, in Carassius auratus proximal renal tubule cells, RVD is activated by an intracellular Ca2+ signal that likely emanates from the ER and not from the extracellular media or the mitochondrial Ca2+ pool. Ca2+ activation of a cAMP-modulated osmoregulatory K+ channel appears to play an important role.
Detrusor hyperplasia and expression of "immediate early" genes with onset of abnormal urodynamic parameters
Authors: Karim O. M. , Seki N. , Mostwin J. L.
Published: December 2017

To determine the stimulus for growth of the detrusor with a pathophysiological obstruction to the urinary stream, we studied urodynamic parameters, detrusor weight, detrusor DNA content, and the expression of early growth-related protooncogenes in a model of gradual onset bladder outflow obstruction and reversal of obstruction. Silver jeweler's jump rings were placed loosely round the urethra of immature guinea pigs, allowing an obstruction to develop gradually with animal growth. At 1, 2, 4, and 8 wk after surgery, animals were killed after urodynamic studies under urethan anesthesia. Bladders were removed, and mucosa-free detrusor was weighed and frozen for assay of DNA content and expression of c-fos and c-myc protooncogenes. Results were compared with sham-operated age-matched control animals. One week after surgery there was no change in the urodynamic parameters, detrusor weight, or DNA content. At 2, 4, and 8 wk after placement of the silver rings, animals developed obstructive voiding patterns, an increase in detrusor weight, and total DNA content. The onset of obstructive voiding patterns correlated with transient increased levels of c-fos and c-myc mRNA by Northern blot analysis. Autoradiography of in vivo [methyl-3H]thymidine-labeled detrusor muscle from obstructed animals showed myocyte DNA synthesis and mitosis, implying myocyte hyperplasia. After removal of the silver ring, the obstructive voiding patterns resolved and detrusor weight and DNA content returned to levels of the control animals. These results suggest that in the guinea pig bladder subjected to a gradual onset outflow obstruction, detrusor growth is initiated by the development of obstructive voiding patterns.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of furosemide or acetazolamide infusion on renal handling of lithium: a micropuncture study in rats
Authors: Fransen R. , Boer W. H. , Boer P. , Dorhout Mees E. J. , Koomans H. A.
Published: December 2017

Renal lithium (Li) handling was studied by micropuncture at the late proximal (LPT) and early distal (EDT) tubules in control rats and rats infused with furosemide (FUR) or acetazolamide (ACTZ). In control rats, the tubular fluid-to-plasma Li concentration ratio [(T/P)Li] at the LPT exceeded unity (1.05 +/- 0.02, P < 0.05). Some 25% of the filtered load (FL) of Li and water was reabsorbed in proportion between the LPT and the EDT, and consequently the (T/P)Li at the EDT (1.03 +/- 0.03) did not change. FUR inhibited Li reabsorption in the proximal convoluted tubules (PCT), by approximately 7% of the FL. Reabsorption of Li and water in the loop segment was also inhibited, virtually in proportion, by approximately 10% of the FL. These data suggest that FUR-sensitive Li reabsorption in the loop mainly takes place in the pars recta. However, a small increase in the (T/P)Li at the EDT (to 1.10 +/- 0.01) suggested inhibition of some Li transport (approximately 2% of the filtered load of Li) without water, most likely in the thick ascending limb (TAL). In the PCT, ACTZ reduced Li reabsorption by approximately 16% of its FL. Although it is likely that ACTZ also inhibited the pars recta, net Li reabsorption in the loop was not reduced. This suggests that TAL Li reabsorption can compensate for increased delivery.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of galanin on food intake in rats: involvement of lateral and ventromedial hypothalamic sites
Authors: Schick R. R. , Samsami S. , Zimmermann J. P. , Eberl T. , Endres C. , Schusdziarra V. , Classen M.
Published: December 2017

Galanin has previously been reported to elicit feeding in satiated animals when injected into the hypothalamic paraventricular nucleus. It is not known, however, 1) whether this action is due to activation of feeding signals or suppression of satiety signals or both or 2) whether other hypothalamic regions such as the lateral hypothalamus (LH) or the ventromedial hypothalamus (VMH) are involved in this action. The effects of galanin on food intake were therefore examined in satiated and in fasted rats both after intracerebroventricular injection (0.1, 1, and 10 micrograms/10 microliters) and after microinjection (1 and 5 micrograms/0.5 microliters) into the LH and VMH. Twenty minutes after intracerebroventricular injection, galanin significantly and dose dependently augmented food intake by up to sevenfold in freely feeding rats and by up to 79% in fasted animals. The galanin-induced augmentation of cumulative food intake up to 2 h after injection was due to the initial increase in food consumption during the 0 to 20-min interval. This suggests that galanin acts by activation of feeding behavior and not by suppression of satiety signals in these fasted animals, in which satiety signals are presumably not initially operative. Twenty minutes after intrahypothalamic injections into both the LH and VMH, galanin (5 micrograms) significantly increased food consumption, fivefold in freely feeding rats and 30-35% in fasted rats. Thus stimulation of feeding by centrally injected galanin also involves loci within the LH and VMH.
Mechanisms for the diuresis of acute cold exposure: role for vasopressin?
Authors: Allen D. E. , Gellai M.
Published: December 2017

The hypothesis that inhibition of vasopressin (VP) secretion initiates cold-induced diuresis was tested in six Brattleboro homozygous (diabetes insipidus, DI) rats exposed to 60 min at 5 degrees C. For 9-14 days before cold exposure (CE) the rats were treated with VP (750 pg.kg-1.min-1) subcutaneously via osmotic minipumps. Eight vehicle-treated Long-Evans (LE) rats characterized the response to acute exposure at 5 degrees C. Additional groups of six to eight LE and six DI rats were infused with VP (30-90 pg.kg-1.min-1 iv) on the day of CE. The DI rats receiving chronic VP replacement and untreated LE rats exhibited cold-induced diuresis, with peak increases in urine flow (V) of 63 +/- 12 (DIs) and 29 +/- 4 (LEs) microliters.min-1 x 100 g body wt-1. LE rats acutely infused with VP exhibited a diuresis at the two lower doses (peak V was 18 +/- 3 at the 30 and 18 +/- 4 microliters.min-1 x 100 g body wt-1 at the 60 pg.kg-1.min-1 dose), but the diuretic response was completely blunted at the uppermost dose of VP. Cold-induced diuresis was absent at the lowest VP dose in the acutely infused DI rats. A pressor response (30-36 mmHg) to CE was noted with all treatment groups, including those that did not exhibit a diuresis. No changes in glomerular filtration rate (GFR) with CE were observed. These data suggest that when plasma VP levels are controlled by prolonged infusion of VP in the DI rats, other mechanisms can operate to initiate cold-induced diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)
Intrauterine growth retardation and fetal losses are caused by epidermal growth factor deficiency in mice
Authors: Kamei Y. , Tsutsumi O. , Kuwabara Y. , Taketani Y.
Published: December 2017

The plasma concentration of epidermal growth factor (EGF) in female mice increases during pregnancy. Sialoadenectomy (surgical removal of the submandibular glands) on day 13 of gestation attenuates the rise in plasma EGF and significantly reduces the percent of live pups on day 19 of pregnancy to 80% compared with 95% for the control animals. EGF replacement therapy given to the sialoadenectomized mice successfully prevented this reduction in the percent of live pups on day 19. The average weight of the live fetuses from sialoadenectomized mothers was significantly lower than those from the control mothers, i.e., 1.00 +/- 0.14 (SD) g vs. 1.13 +/- 0.07 g. The administration of anti-EGF antiserum to the sialoadenectomized mice further affected fetal viability; only 70% of the pups were alive on day 19, with a mean weight of 0.93 +/- 0.15 g. The mean weight of the fetal body and that of the liver caused by sialoadenectomy were similarly reduced, but the brain was not affected, which shows that the growth retardation was asymmetrical. These findings suggest that EGF plays a physiological role in fetal growth and that EGF deficiency may be a cause of asymmetrical intrauterine growth retardation, which might be due to uteroplacental dysfunction.
Blockade of brain bombesin/GRP receptors increases food intake in satiated rats
Authors: Merali Z. , Moody T. W. , Coy D.
Published: December 2017

The mechanisms that initiate or terminate a meal remain obscure. Bombesin (BN) and gene-related peptides (GRP) have been reported to induce a satiety-like state in several species including fowl, mouse, rat, wolf, pig, baboon, and humans. The evolutionary conservation of this pharmacological response suggests a physiological role for the endogenous BN-like peptide(s) in the regulation of food intake. If the release of BN-like peptide(s) represents a "satiety signal" then pharmacological antagonism of this action should enhance food intake and/or postpone satiety. We report herein 1) that [Leu14, psi 13-14]-BN, a BN receptor antagonist, blocks the suppressive effect of centrally administered BN on food intake and 2) that in satiated rats, this pseudopeptide enhances food intake; the effects were more potent and efficacious upon the fourth compared with the third ventricular administration. These results support the contention that endogenous BN-like peptides mediate satiety and that this effect involves brain BN receptors in the caudal brain stem site(s).
Coronary blood flow in vivo in the coho salmon (Oncorhynchus kisutch)
Authors: Axelsson M. , Farrell A. P.
Published: December 2017

The effects of adrenergic agonists on dorsal aortic blood pressure, cardiac output, and coronary blood flow were studied in unrestrained coho salmon, Oncorhynchus kisutch. Resting coronary blood flow was 0.43 ml.min-1.kg body mass-1, which represented 1.1% of cardiac output or approximately 0.5 ml.min-1.g-1 compact ventricular mass calculated on 40% of total ventricle mass. Coronary blood flow was phasic and continuous throughout the cardiac cycle; flow seems to be affected by the ventricular contraction, with a peak flow occurring during diastole and a nadir in early systole. Epinephrine injections into the dorsal aorta resulted in a rapid increase in coronary blood flow in association with a rapid increase in dorsal aortic blood pressure. Subsequently there was also a slower increase in coronary vascular resistance, which could be blocked by phentolamine, indicating an alpha-adrenergic vasoconstriction. Isoprenaline injection produced an increase in coronary blood flow and a large reduction in coronary vascular resistance. The coronary vasodilatation was blocked by propranolol, indicating that it may be partly due to a beta-adrenergic vasodilatation. Preliminary results showed a marked increase in coronary blood flow associated with exposure to environmental hypoxia.
Endothelium-derived factors modulate contraction of bronchial smooth muscle
Authors: McLarty A. J. , McGregor C. G. , Miller V. M.
Published: December 2017

Experiments were designed to determine how changes in the ratio of specific vascular endothelium-derived factors might affect reactivity of bronchial smooth muscle. The epithelium was mechanically removed from rings of third-order canine bronchi, and the rings were suspended in organ chambers for measurement of isometric force. Rings of pulmonary artery were cut; in some the endothelium was mechanically removed. The arterial rings were everted and pairs, with and without endothelium, were incubated with control solution, NG-monomethyl-L-arginine (L-NMMA), indomethacin, or both L-NMMA and indomethacin for 90 min. They were then inserted into the lumen of the bronchial rings. Cumulative concentration-response curves to acetylcholine and 5-hydroxytryptamine were obtained. There was no significant difference in response between bronchi containing arteries with or without endothelium incubated with control solution. Contractions of bronchi containing arteries without endothelium, incubated in either L-NMMA or indomethacin, increased from control. However, in rings containing arteries with endothelium, incubation with either inhibitor decreased bronchial contractions. Incubation with both inhibitors eliminated the difference. These results suggest that the vascular endothelium produces factors that can both contract and relax bronchial smooth muscle. With inhibition of production of either nitric oxide with L-NMMA or prostanoids with indomethacin, release of other endothelium-derived factors occurs that attenuates contractions of bronchial smooth muscle. Therefore, an imbalance in the ratio of production of endothelium-derived factors may contribute to bronchospastic disorders.
Hormonal and locomotor activity rhythms in rats under 90-min dark-pulse conditions
Authors: Laakso M. L. , Porkka-Heiskanen T. , Leinonen L. , Joutsiniemi S. L. , Mannisto P. T.
Published: December 2017

The ability of a short dark pulse to entrain the circadian rhythms in rats was investigated. Pineal melatonin contents and serum levels of corticosterone and thyrotropin, a thyroid-stimulating hormone (TSH), were measured and locomotor activity was recorded under 12:12-h light-dark cycles (LD; darkness from 1800 to 0600 h) and under a 22.5:1.5 h LD lighting schedule (darkness from 1800 to 1930 h). The 90-min dark pulse was enough to trigger the rise of melatonin synthesis, but a free-running component was detected in the locomotor activity. Corticosterone levels showed diurnal variations under both conditions. The decrease of corticosterone and the increase of melatonin were phase locked, but the corticosterone pattern was distorted under the dark-pulse conditions. The 24-h rhythm of TSH was detectable in the control but not in the dark-pulse schedule. The results suggest that the circadian rhythm of pineal melatonin and the decrease of serum corticosterone levels were entrainable by the dark pulses, whereas the increase of corticosterone, the variations of TSH, and the rhythm of locomotor activity were not.
Febrile and metabolic tolerance to endotoxin and human recombinant interleukin-1 beta in rabbits
Authors: Yamashiro O. , Morimoto A. , Sakata Y. , Watanabe T. , Murakami N.
Published: December 2017

We investigated whether or not tolerance of the febrile and metabolic responses to human recombinant interleukin-1 beta (IL-1 beta) develops in rabbits. Febrile tolerance to bacterial endotoxin was induced by daily injections of lipopolysaccharide (LPS, 5.0 micrograms/kg iv). In LPS-tolerant rabbits, the second phase of the biphasic fever induced by intravenous injections of LPS (5.0 micrograms/kg) or IL-1 beta (2.0 micrograms/kg) was significantly reduced. However, the first phase was almost the same as that observed in normal rabbits. Five daily injections of IL-1 beta (2.0 micrograms/kg iv) resulted in the development of tolerance of the febrile response to IL-1 beta. In IL-1 beta-tolerant rabbits, the second peak of the biphasic fever was significantly reduced. In addition, decreases in leukocyte count and plasma zinc induced by intravenous injections of LPS or IL-1 beta were significantly reduced in LPS- or IL-1 beta-tolerant rabbits. However the monophasic fever induced by a smaller dose of IL-1 beta (0.5 microgram/kg iv) and the first peak of the IL-1 biphasic fever were almost the same as those observed in normal rabbits. Febrile responses induced in LPS- or IL-1 beta-tolerant rabbits by intracerebroventricular injections of LPS (5.0 ng) or IL-1 beta (2.0 ng) were similar to those observed in normal rabbits. The present results suggest that tolerance of the febrile and metabolic responses to IL-1 beta is developed after repeated injections of IL-1 beta and that reduced responsiveness to IL-1 beta is partly involved in the development of LPS tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
In vitro sensitivity of median preoptic neurons to angiotensin II, osmotic pressure, and temperature
Authors: Travis K. A. , Johnson A. K.
Published: December 2017

In vivo experiments suggest an interaction of the mechanisms involved in the regulation of body fluid balance and body temperature. Increases in plasma osmolality initiate drinking and increase the thermal set point for sweating. The median preoptic nucleus (MnPO) has anatomical connections with brain areas important in fluid balance and cardiovascular regulation and, with the preoptic-anterior hypothalamus, a thermoregulatory region. The present experiments employed in vitro single-unit recordings to determine the sensitivity of MnPO neurons to angiotensin II (ANG II), changes in osmotic pressure, and changes in temperature. One-fifth (11 of 55) of the MnPO neurons responded with changes in firing rate during the ANG II treatment, one-fourth (19 of 75) responded to changes in perfusate osmolality, and there was a significant effect of osmolality and ANG II on the thermosensitivity of 25% of the neurons tested.
Estrogens and antiestrogens: actions and interactions with fluphenazine on food intake and body weight in rats
Authors: Gray J. M. , Schrock S. , Bishop M.
Published: December 2017

Treatment of ovariectomized rats for 3 days with 2 micrograms estradiol benzoate (E2B), 6 micrograms ethinyl estradiol, or 1-2 mg of either of the antiestrogens nafoxidine or tamoxifen led to similar decreases in food intake, body weight gain, adipose tissue lipoprotein lipase activity, and hepatic fatty acid synthetase activity, despite their different effects on uterine growth and induction of progestin receptors in pituitary and adipose tissue. Longer-term (2 wk) treatment with tamoxifen resulted in similar transient changes in food intake and body weight gain, as did treatment with E2B. Daily administration of 50 micrograms fluphenazine (FLU) led to significant decreases in body weight, although there was no change in food intake. Concurrent administration of FLU with either E2B or tamoxifen led to additive effects on body weight and food intake change. None of the treatments had any effect on in vitro binding of [3H]tamoxifen to antiestrogen binding sites in pooled hypothalamic-preoptic area samples.
ANP inhibits NaCl absorption and elicits Cl secretion in porcine colon: evidence for cGMP and Ca mediation
Authors: Argenzio R. A. , Armstrong M.
Published: December 2017

The effects of atrial natriuretic peptide (ANP) on ion transport were examined in the isolated, short-circuited proximal colon epithelium of the pig. Addition of ANP to the serosal solution decreased the rate of neutral Na and Cl absorption and elicited electrogenic Cl secretion. Amiloride, at a concentration that inhibits Na-H exchange, produced an identical inhibition of Na transport and abolished the ANP-induced decrease in Na absorption. In contrast, serosal addition of bumetanide, an inhibitor of Na-K-2Cl cotransport, partially inhibited the short-circuit current (Isc) response to ANP. Whereas 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) produced qualitatively similar effects as ANP, relatively high concentrations of N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP) or prostaglandin E2 were required to alter NaCl transport. Furthermore, incubation of colonic mucosa with ANP induced a threefold increase in cGMP content, whereas cAMP was unaffected. The ANP-induced Cl secretion and Isc were diminished with tetrodotoxin and verapamil, whereas these agents were without effect on the ANP-induced inhibition of Na and Cl absorption. Results indicate that ANP inhibits net colonic absorption of ions by antiabsorptive and secretory mechanisms that are dependent on both cGMP and Ca.
Role of prostaglandins in renal sensory receptor activation by substance P and bradykinin
Authors: Kopp U. C. , Smith L. A.
Published: December 2017

In anesthetized rats increasing ureteral pressure results in an increase in ipsilateral afferent renal nerve activity and a reflex increase in contralateral urine flow rate and urinary sodium excretion that is dependent on intact prostaglandin synthesis. Activation of renal pelvic substance P receptors contributes to the renorenal reflex responses to increased ureteral pressure. Because these data suggested that renal sensory receptors could be activated by both prostaglandins and substance P we examined whether activation of renal sensory receptors by substance P was dependent on intact prostaglandin synthesis. The renal pelvis was perfused with capsaicin, 2.5 micrograms/ml, or substance P, 4 micrograms/ml, before and during renal pelvic perfusion with the prostaglandin synthesis inhibitor indomethacin, 50 micrograms/ml. Indomethacin reduced the peak ipsilateral afferent renal nerve activity responses to capsaicin and substance P by 83 +/- 15% and 81 +/- 8%, respectively, as well as the contralateral diuretic and natriuretic responses. We also examined the effects of renal pelvic administration of indomethacin on the responses to renal pelvic perfusion with bradykinin. Bradykinin, 20 micrograms/ml, increased peak ipsilateral afferent renal nerve activity by 197 +/- 47% and contralateral urine flow rate and urinary sodium excretion by 31 +/- 6 and 20 +/- 6%, respectively. Indomethacin reduced the ipsilateral afferent renal nerve activity response by 76 +/- 9% and abolished the contralateral diuretic and natriuretic responses to bradykinin. We conclude that renal sensory receptor activation by capsaicin, substance P, and bradykinin is dependent on intact renal prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Tamoxifen antagonizes the effects of estradiol on energy balance and estrous behavior in Syrian hamsters
Authors: Wade G. N. , Powers J. B.
Published: December 2017

Ovariectomized Syrian hamsters were treated with estradiol benzoate (5 micrograms/day for 4 wk), tamoxifen (500 micrograms/day), an antiestrogen that competes with estradiol for central and peripheral estrogen receptors, or both estradiol benzoate and tamoxifen. As expected, estradiol treatment caused significant decreases in body weight and fat content without affecting food intake. Given alone, tamoxifen had no effect on body weight or composition, but when given concurrently, tamoxifen significantly attenuated the effects of estradiol. These results stand in contrast to findings in rats where nonsteroidal antiestrogens, including tamoxifen, mimic the effects of estradiol on body weight and energy metabolism and are completely devoid of any antiestrogenic actions. As in rats, tamoxifen was a potent inhibitor of estrous behavior, whether induced with estradiol alone or with sequential treatment with estradiol and progesterone. Again, as in rats, tamoxifen acted as an antagonist and a weak estrogen agonist on uterine weight. These findings support the notion that the relative agonistic and antagonistic actions of tamoxifen, and other antiestrogens, vary with species and with the estrogen-sensitive endpoint being investigated.
Role of arteria baroreceptor input on thirst and urinary responses to intracerebroventricular angiotensin II
Authors: Thunhorst R. L. , Lewis S. J. , Johnson A. K.
Published: December 2017

Intracerebroventricular (icv) infusion of angiotensin II (ANG II) in rats elicits greater water intake under hypotensive, compared with normotensive, conditions. The present experiments used sinoaortic baroreceptor-denervated (SAD) rats and sham-operated rats to examine if the modulatory effects of arterial blood pressure on water intake in response to icv ANG II are mediated by arterial baroreceptors. Mean arterial blood pressure (MAP) was raised or lowered by intravenous (i.v.) infusions of phenylephrine (1 or 10 micrograms.kg-1 x min-1) or minoxidil (25 micrograms.kg-1 x min-1), respectively. The angiotensin-converting enzyme inhibitor captopril (0.33 mg/min) was infused i.v. to prevent the endogenous formation of ANG II during testing. Urinary excretion of water and solutes was measured throughout. Water intake elicited by icv ANG II was inversely related to changes in MAP. Specifically, rats drank more water in response to icv ANG II when MAP was reduced by minoxidil but drank less water when MAP was elevated by phenylephrine. The influence of changing MAP on the icv ANG II-induced drinking responses was not affected by SAD. These results suggest that the modulatory effects of arterial blood pressure on icv ANG II-induced drinking can occur in the absence of sinoaortic baroreceptor input.