bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of sodium and chloride transport in the thick ascending limb in the avian nephron
Authors: Osono E. , Nishimura H.
Published: December 2017

We previously reported that birds may concentrate urine by a countercurrent multiplier mechanism using single-solute (NaCl) recirculation, in which the thick ascending limb of Henle (TAL) of mammalian-type nephrons provides an energy source. The Japanese quail TAL has a higher lumen-to-bath Cl flux (JCl,lb) than that of mammals; the mechanism for maintaining the osmotic gradient along the medullary cone is unknown. We investigated whether salt delivery alters the NaCl reabsorption rate in the TAL dissected from both normal and salt-loaded Japanese quail, Coturnix coturnix, 3-7 wk old. When salt loading to the TAL was increased by increasing the perfusion flow rate (PFR), the lumen-to-bath Na and Cl flux coefficients (KNa,lb or KCl,lb, 10(-7) cm2/s) increased, respectively (P < 0.05), from 5.1 +/- 0.9 to 7.6 +/- 0.7 and from 6.8 +/- 0.9 to 8.9 +/- 1.4. Ouabain addition significantly reduced the KNa,lb. A significant correlation existed between PFR and JCl,lb (r = 0.69, P < 0.01) and PFR and JNa,lb. When the TAL was perfused at a low PFR, increasing Cl concentration in the perfusate and bathing medium from 125 to 175 (P < 0.05) or 225 mM (P < 0.01) increased JCl,lb but not KCl,lb, while decreasing Cl concentration decreased JCl,lb but not KCl,lb. Salt loading of intact birds (0.2 M NaCl drinking water) for 7 days increased the plasma Na level and the cloacal fluid-to-plasma osmolality ratio from 0.28 +/- 0.07 to 1.06 +/- 0.05 (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Voluntary intake of calcium and other minerals by rats
Authors: Tordoff M. G.
Published: December 2017

The voluntary intake by male Sprague-Dawley rats of five calcium salts and eight mineral chlorides was assessed. Groups of 12-25 rats received a series of 48-h two-bottle tests with a choice between water and ascending concentrations of a mineral solution. Similar inverted U-shaped concentration-intake functions were obtained with each of the five calcium salts tested (hydroxide, gluconate, phosphate, lactate, and chloride): rats drank more calcium solution than water at concentrations between approximately 0.2 and 5 mM, showed indifference between 5 and 12 mM, and avoided higher concentrations. Inverted U-shaped concentration-intake functions were also obtained for ammonium chloride (peak at 100 mM), magnesium chloride (peak at 10 microM), potassium chloride (peak at 10 mM), ferrous chloride (peak at 4.64 microM), and rubidium chloride (peak at 2.15 mM). Rats drank slightly and nonsignificantly more 2.15 microM aluminum chloride than water and never drank more zinc chloride than water (range tested, 1 microM to 464 mM). These results illustrate that, as is the case for sodium, rats spontaneously ingest low concentrations of calcium and several other mineral solutions in preference to water. In general, the lower the cation's ionic charge, the greater the intake and higher the most accepted concentration.
Increased endothelium-dependent renal vasodilation in cirrhotic rats
Authors: Garcia-Estan J. , Atucha N. M. , Sabio J. M. , Vargas F. , Quesada T. , Romero J. C.
Published: December 2017

We have evaluated the renal blood flow (RBF) response of cirrhotic rats to endothelium-dependent [acetylcholine (ACh)] and -independent [sodium nitroprusside (NP)] vasodilators. In anesthetized rats, ACh dose dependently increased RBF, but the response of the cirrhotic rats (n = 6) was significantly higher than that of the controls (n = 6). NP also increased RBF in a dose-dependent manner, but there were no differences between both groups. NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg i.v.) significantly reduced the responses to ACh in both groups, but those of the cirrhotic rats were still higher than those of the controls. In experiments performed in isolated perfused kidneys, preconstricted with phenylephrine, dose-response curves for ACh and NP were obtained in the presence of indomethacin. Both ACh and NP decreased renal perfusion pressure dose dependently, but only the response of the cirrhotic rats (n = 5) to ACh was significantly higher than that of the controls (n = 5). L-NAME (100 microM) significantly reduced the responses to ACh and increased those of NP and abolished the differences between groups, except at the high dose of ACh. These results demonstrate an elevated endothelium-dependent vasodilator response in the cirrhotic kidney, which is eliminated by combined prostaglandin and nitric oxide (NO) synthesis inhibition and suggest that increased intrarenal activity of NO may be contributing to the renal alterations of liver cirrhosis.
Intestinal capsaicin transiently attenuates suppression of sham feeding by oleate
Authors: Tamura C. S. , Ritter R. C.
Published: December 2017

Intraintestinal infusion of oleic acid reduces food intake in rats and other mammals. The neural mechanisms that mediate this behavioral response to intestinal stimulation are incompletely appreciated. We have found that intraintestinal infusion of capsaicin reduces sham feeding. In addition, 24 h after a single intestinal capsaicin infusion, reduction of sham feeding by intestinal oleate infusion was attenuated. However, by 48 h post-capsaicin, suppression of sham feeding by oleate had returned to pre-capsaicin levels. Repeated intestinal administration of capsaicin produced less attenuation of oleate-induced suppression of sham feeding, suggesting the development of tolerance to capsaicin. Unlike systemic capsaicin, intestinal capsaicin does not impair cholecystokinin-induced reduction of feeding or the corneal chemosensory reflex. Furthermore, there are no histochemical signs of vagal sensory degeneration in the hindbrain after intraintestinal capsaicin. Our results suggest that a capsaicin-sensitive substrate in or near the intestine is responsible for mediating the reduction of sham feeding by intestinal oleate infusion.
Opioid growth factor inhibits DNA synthesis in mouse tongue epithelium in a circadian rhythm-dependent manner
Authors: Zagon I. S. , Wu Y. , McLaughlin P. J.
Published: December 2017

In addition to neuromodulation, endogenous opioids also serve as growth factors. To investigate the involvement of the naturally occurring opioid peptide [Met5]enkephalin [termed opioid growth factor (OGF)] in the renewal of epithelium, adult mice were given systemic injections of OGF (1 mg/kg) and examined 2 h later at 0700 or 1700 h. DNA synthesis in the tongue was investigated using [3H]thymidine and autoradiography. OGF depressed DNA synthesis of the basal epithelial cells in the tip, and dorsal and ventral surfaces of the tongue (42-44% of control levels) only at 0700 h. This decrease in DNA synthesis was blocked by concomitant administration of the opioid antagonist naloxone (10 mg/kg); naloxone alone had no influence on cell replicative processes. Both OGF and its receptor, zeta (zeta), were detected in the stratified squamous epithelium of the ventral and dorsal surfaces of the tongue by immunocytochemistry. Photodensitometric measurements of immunocytochemical preparations revealed almost twofold more OGF and zeta-receptor immunoreactivity at 1700 h than at 0700 h. These results indicate that an endogenous opioid peptide and its receptor are present and govern cellular renewal processes in the tongue and regulate DNA synthesis in a circadian rhythm-dependent fashion.
Central effects of glucocorticoid receptor antagonist RU-38486 on lipopolysaccharide and stress-induced fever
Authors: McClellan J. L. , Klir J. J. , Morrow L. E. , Kluger M. J.
Published: December 2017

Intracerebroventricular administration of the glucocorticoid type II receptor antagonist RU-38486 leads to an increased fever after injection of lipopolysaccharide (LPS) in awake unrestrained rats, indicating that endogenous glucocorticoids act centrally to lower temperature after the intraperitoneal injection of LPS. The current study examined where in the brain glucocorticoids exert these effects on fever and if these effects involve plasma interleukin-6 and corticosterone. RU-38486 injected intracerebroventricularly (10 ng/animal) led to a significantly greater rise in biotelemetered body temperature (BT) 120-240 min post-LPS (50 mg/kg ip) compared with controls (0.89 +/- 0.14 vs. 0.44 +/- 0.22 degree C, P = 0.0482), confirming our earlier study, and also led to a significantly greater rise in BT after exposure to an open field when the RU-38486 was infused intracerebroventricularly (10 ng/ml, 1 microliter/h) for 20 h before the exposure (1.48 +/- 0.18 vs. 1.06 +/- 0.11 degree C, P = 0.023). When rats were injected with RU-38486 into the anterior hypothalamus (1 ng/animal), there was an increased rise in BT after injection of LPS (1.74 +/- 0.27 vs. 0.82 +/- 0.22 degree C, P = 0.0075) but not after exposure to an open field (1 ng intrahypothalamically, 1 h preexposure). There were no differences in plasma interleukin (IL)-6-like activity or plasma corticosterone after intracerebroventricular injection of RU-38486 and intraperitoneal injection of LPS. We conclude that endogenous glucocorticoids are working centrally to modulate fever after LPS and exposure to open field, and that LPS-induced fever is modulated by glucocorticoids in the anterior hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)
Two pathways for choline transport in eel erythrocytes: a saturable carrier and a volume-activated channel
Authors: Joyner S. E. , Kirk K.
Published: December 2017

Choline transport in eel (Anguilla anguilla) erythrocytes was investigated in cells suspended in isotonic and hypotonic media. In cells in isosmotic solution choline transport was mediated by a saturable system with a Michaelis constant (Km; 62 +/- 6 microM) similar to that of the choline carrier of human erythrocytes but a maximal transport rate (Vmax; 4.5 +/- 0.4 mmol.1 red blood cells-1.h-1) almost two orders of magnitude higher than that in human red blood cells. This pathway was inhibited by hemicholinium-3 and dodecyltrimethylammonium, but not by any of a range of anion transport inhibitors tested. Swelling the cells by suspending them in hyposmotic media activated a second choline transport component that was kinetically and pharmacologically distinct from the saturable system. The volume-activated component was nonsaturable (up to 50 mM choline). It was not inhibited by hemicholinium-3 or dodecyltrimethylammonium but was inhibited by anion transport inhibitors, the most potent of which was 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB; half-maximal inhibitory concentration = 14 microM). Dose-response curves for the effect of NPPB on swelling-activated choline transport and the swelling-activated transport of taurine, a sulfonic amino acid, were superimposable. It is postulated that the transport of choline and taurine (as well as that of other small organic solutes) in osmotically swollen fish erythrocytes is mediated by a volume-activated, anion-selective channel.
Comparison of fos-like immunoreactivity induced in rat brain by central injection of angiotensin II and carbachol
Authors: Rowland N. E. , Li B. H. , Rozelle A. K. , Smith G. C.
Published: December 2017

Rats were given intracerebroventricular injections of either angiotensin II (ANG II) or the cholinomimetic carbachol. Some rats received cotreatment with ANG II antagonists selective for either angiotensin receptor AT1 (losartan) or AT2 (PD-123319, CGP-42112A). One hour later, the rats were killed and the brains processed for immunocytochemical detection of Fos-like immunoreactivity (FLI). ANG II treatment induced strong FLI in the anterior subfornical organ (SFO), median preoptic nucleus (MnPO), organum vasculosum laminae terminalis (OVLT), and supraoptic and paraventricular hypothalamic nuclei (SON, PVH). The AT1 antagonist abolished FLI in all regions normally stimulated by ANG II. The AT2 antagonist PD-123319 reduced FLI in SON and PVH, but CGP-42112A was less effective. Carbachol induced strong FLI in SON, PVH, and MnPO and only moderate FLI in SFO and OVLT. The AT1 antagonist prevented carbachol-induced FLI in the MnPO only. The distributions of FLI are compared between these central dipsogens and with that previously reported after peripheral infusion of ANG II, and their implications for mapping central thirst pathways are discussed.
Arterial mechanics in the fin whale suggest a unique hemodynamic design
Authors: Shadwick R. E. , Gosline J. M.
Published: December 2017

An analysis of the dimensions of the aortic tree and the mechanical properties of arterial wall tissues in the fin whale (Balaenoptera physalus) is presented. The aortic arch is greatly expanded, having an internal radius at an estimated mean blood pressure (13 kPa) that is 2.5 times greater than that of the descending thoracic aorta. At this pressure, the elastic modulus of the arch wall (0.4 MPa) is 30 times less than that of the descending aorta (12 MPa). Consequently, even though some capacitance is provided anteriorly by the relatively compliant innominate and carotid arteries, > 90% of the arterial capacitance resides in the arch. The characteristic pressure wave velocity (C0) and impedance (Z0) were calculated from vessel dimensions and elasticity. A predicted 20-fold increase in Z0 between the arch and thoracic aorta should provide a major reflecting site, effectively uncoupling the arch from the remainder of the arterial tree. The dimensions of the arch relative to the likely pressure wavelengths within it suggest that it acts like a compliant windkessel that greatly reduces the pulsatility of the inflow to the descending aorta, which itself likely acts as a rigid, tapered manifold. It is suggested that the presence of both a highly compliant arch and a relatively rigid descending aorta is an adaptation for diving.
Synergistic effect of rhTNF-alpha and rhIL-1 alpha in inducing anorexia in rats
Authors: Yang Z. J. , Koseki M. , Meguid M. M. , Gleason J. R. , Debonis D.
Published: December 2017

To investigate whether there is a synergistic effect of recombinant human tumor necrosis factor-alpha (rhTNF-alpha) and recombinant human interleukin-1 alpha (rhIL-1 alpha) in inducing anorexia, 32 rats with jugular catheters were studied (8 rats/group): controls received normal saline; the IL-1 group received rhIL-1 alpha (10 micrograms/kg); the TNF group received rhTNF-alpha (30 micrograms/kg); and the IL-1 + TNF group received the same concentration of both rhIL-1 alpha+rhTNF-alpha for 3 days; solutions were then switched to normal saline. No significant decrease in light- and dark-phase food intake occurred during infusion of subeffective rhTNF-alpha. Food intake was decreased on the first rhIL-1 alpha infusion day because of a decreased meal number during the dark phase. A significant decrease in food intake occurred with combined infusion of rhIL-1 alpha+rhTNF-alpha because of a reduction in meal number during dark phase and meal size during light phase. Our results show that rhIL-1 alpha and rhTNF-alpha, when administered concurrently, had a synergistic effect in inducing anorexia, suggesting that low concentrations of these cytokines as produced endogenously may have potential effects on other biological functions in vivo.
Hypothalamic thermal stimulation modulates vasopressin release in hyperosmotically stimulated rabbits
Authors: Keil R. , Gerstberger R. , Simon E.
Published: December 2017

Under thermoneutral conditions conscious rabbits received systemic infusions of NaCl as hypertonic solution (90 mueq.min-1.kg body wt-1), which raised their plasma osmolality from 283 to 312 mosmol/kgH2O. Rabbits receiving isotonic saline served as controls. Hypertonic stimulation induced a 60% reduction of both respiratory frequency and evaporative water loss. Rectal temperature rose by 0.4 degrees C despite enhanced peripheral vasodilation as indicated by increased ear skin temperature. Plasma vasopressin (AVP), aldosterone (ALDO), and corticosterone (COR) were significantly elevated from 6 to 16 pg/ml, 90 to 180 pg/ml, and 17 to 40 ng/ml, respectively. To elucidate the importance of central temperature for AVP and adrenal corticosteroid release, hypothalamic thermal stimulations (20 min) were superimposed during established iso- and hyperosmotic steady-state conditions. Different from isosmotic controls, hyperosmotic animals responded to hypothalamic cooling (37 degrees C) with a significant decrease in plasma AVP from 16 to 13 pg/ml and to hypothalamic warming (41 degrees C) with a significant rise from 16 to 19 pg/ml. A weak temperature effect on COR release was also disclosed, especially of hypothalamic cooling, which significantly lowered plasma COR from 42 to 34 ng/ml. These results provide evidence for positive local temperature coefficients of hypothalamic control of AVP release and suggest a similar property also for the control of COR release by the hypothalamo-adenohypophysial axis.
Pre- and postnatal effects of photoperiod on collared lemmings (Dicrostonyx groenlandicus)
Authors: Gower B. A. , Nagy T. R. , Stetson M. H.
Published: December 2017

We investigated the hypothesis that photoperiod information received during the prenatal and/or early postnatal periods influences subsequent development in collared lemmings. Pregnant lemmings were exposed to either a short [8:16-h light-dark cycle (8:16)] or long (22:2) photoperiod throughout gestation. On the day of birth, pups were cross-fostered to dams housed in either short or long photoperiod. After an 11-day experimental lactational period (LACT), all animals were transferred to an intermediate photoperiod (16:8), the response to which depends on prior photoperiod exposure. Pups remained on this photoperiod until death at postnatal day 90. Information received during gestation (GEST) influenced offspring growth, pelage color, guard hair length, presence of the bifid claw at weaning, testes mass at 10 wk postweaning, and serum prolactin (PRL). Parameters measured at weaning reflected directly the photoperiod experienced during GEST (e.g., short-day GEST pups had white pelage). Conversely, parameters measured at 10 wk postweaning reflected the change in photoperiod experienced between GEST and 16:8 (e.g., short-day GEST young had gray pelage, indicative of an increase in photoperiod). Information received during LACT influenced growth and the presence of the bifid claw at weaning.
Constant light suppresses sleep and circadian rhythms in pigeons without consequent sleep rebound in darkness
Authors: Berger R. J. , Phillips N. H.
Published: December 2017

Sleep patterns and circadian rhythms of body temperature, activity, body weight, and electroencephalographic (EEG) power spectra of pigeons were compared among three photic conditions: a 12:12-h light-dark cycle (LD), followed successively by constant bright (LL) and dim light (DD) periods. LL suppressed non-rapid-eye-movement and rapid eye movement sleep and circadian rhythms of the measured variables without producing increased drowsiness or other physiological or behavioral changes. Sleep patterns after LL-DD transitions also showed no evidence of prior sleep deprivation during LL. Sleep latency after LL-DD transitions was 93 min longer than after L-D transitions in LD. Total sleep and EEG slow wave activity during the first 24 h in DD did not differ from D in LD. Free-running circadian rhythms subsequently reappeared in DD after LL.
Effect of caloric content and composition of a liquid meal on gastric emptying in the rat
Authors: Maerz L. L. , Sankaran H. , Scharpf S. J. , Deveney C. W.
Published: December 2017

We examined the effect of caloric content and substrate composition on gastric emptying in conscious Sprague-Dawley rats using gastric radioscintigraphy. Three-milliliter volumes of normal saline, glucose, casein hydrolysate, or intralipid containing 0, 1, 2, 3, or 6 kcal labeled with 99mTc-diethylenetriaminepentaacetic acid were given intragastrically. Gamma-camera imaging and computer analysis allowed construction of gastric emptying curves constructed over many time points for each emptying study. There was no difference in the half-emptying times (t1/2) between different substrates with equal calories, and increasing calories significantly prolonged gastric emptying for all substrates. Emptying occurred in a linear fashion with meals containing calories. With 3-ml meals containing 2, 3, or 6 kcal, the rate of delivery of calories to the duodenum is constant regardless of substrate or change in caloric content. We conclude that the rate of caloric delivery to the small intestine with gastric infusion of 1-6 kcal is relatively constant despite differences in total caloric load, substrate composition, and osmolarity.
Thromboxane A2-prostaglandin H2 and renovascular hypertension in rats
Authors: Boussairi E. H. , Sacquet J. , Sassard J. , Benzoni D.
Published: December 2017

To evaluate the contribution of thromboxane (Tx) A2-prostaglandin (PG) H2 in two-kidney, one-clip Goldblatt hypertension (GH), 26 GH rats were chronically treated (GHT) with a specific TxA2-PGH2 receptor antagonist, CGS-22652 (30 mg.kg-1.24 h-1 sc); 28 others as well as 17 sham-clipped (SC) rats received vehicle. Twelve GH and 3 GHT rats developed malignant hypertension and died. After 6 wk of treatment, GH rats exhibited higher mean blood pressure (BP; 189 +/- 3 vs. 118 +/- 2 mmHg) and an increased vascular reactivity to the main pressor agents compared with SC rats. Chronic TxA2-PGH2 receptor blockade lowered mean BP in 13 GHT rats (125 +/- 3 mmHg) and decreased their vascular reactivity compared with GH rats. However, 10 GHT rats remained hypertensive (190 +/- 9 mmHg) and differed from the former by an increased vascular reactivity to vasopressin. It is concluded that renal artery clipping induces either benign or malignant hypertension. In benign forms, TxA2-PGH2 blockade normalizes BP through decreasing the vascular responsiveness to the main pressor agents. In malignant forms, it limits the elevation of BP and markedly reduces mortality.
Sympathetic nervous activity and arterial blood pressure control in conscious rat during rest and behavioral stress
Authors: Randall D. C. , Brown D. R. , Brown L. V. , Kilgore J. M.
Published: December 2017

The object of this experiment is to analyze the neural control of arterial blood pressure (BP) during rest and a sudden behavioral stress. Sprague-Dawley rats were classically conditioned by following a 15-s tone (CS+) with a 0.5-s tail shock. Bipolar renal nerve electrodes and a caudal artery catheter were implanted. Two days later BP and sympathetic nervous activity (SNA) were recorded in the behaviorally trained animals. The CS+ evoked a large initial increase in BP (peak, 14 +/- 5 mmHg, mean +/- SD; n = 12) that lasted 3.9 +/- 0.8 s. An abrupt (latency = 0.16 +/- 0.03 s), short (duration = 0.58 +/- 0.12 s), and intense (4.09 +/- 1.02 times average control) burst in sympathetic activity preceded this first component (C1) of the BP conditional response. The size of C1 was related to the magnitude of the SNA burst. SNA then fell below control; this quiet period preceded a fall in BP after the C1 peak. Pressure rose again (C2; peak = 6 +/- 3 mmHg, average increase = 3 +/- 3 mmHg) for the remainder of the CS+. SNA increased to 1.24 +/- 0.14 of control during this second component of the BP conditional response. Ganglionic blockade eliminated the BP and SNA conditional response (n = 3). The C1 pressure increase appears to result from an “open-loop” process in which a brief barrage of nerve activity governs BP changes lasting several seconds. The quite period probably results from a negative feedback (i.e., baroreflex) relationship between SNA and BP.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of acute ethanol intoxication on glucoregulation during prolonged insulin-induced hypoglycemia
Authors: Molina P. E. , Jabbour K. , Williams P. , Abumrad N. N.
Published: December 2017

This study examined the interaction of acute ethanol administration on glucose homeostasis during insulin-induced hypoglycemia (IIH). Glucose kinetics and net hepatic balances of alanine, glycerol, and lactate were estimated in three groups of dogs: group I underwent 3 h of IIH; group II received a continuous ethanol infusion in addition to IIH; group III received ethanol for 3 h. In group I, IIH resulted in a sustained twofold increase in glucose rate of appearance (Ra) and net hepatic uptake (NHU) of glycerol and lactate but no change in NHU of alanine. In group II, glucose Ra rose transiently, NHU of alanine and glycerol increased two- and fivefold, respectively, whereas NHU of lactate dropped 60%. In group III, no alterations in plasma glucose levels, glucose Ra, and NHU of alanine and glycerol were observed, but NHU of lactate switched to a net output. These results demonstrate that ethanol alone or with IIH exclusively inhibited NHU of lactate, and this was responsible, in a stoichiometric fashion, for the failure of the delayed increase in glucose Ra during IIH.
Differential control of ventilation among inbred strains of mice
Authors: Tankersley C. G. , Fitzgerald R. S. , Kleeberger S. R.
Published: December 2017

The role genetic factors play in ventilatory control was examined by challenging eight inbred strains of mice to acute hypercapnia under normoxic and hypoxic conditions. Age-matched mice were exposed for 3-5 min to inspired gases of the following composition (FICO2:FIO2) 0.03:0.10, 2) 0.03:0.21, 3) 0.08:0.10, and 4) 0.08:0.21, with intermittent room air exposures. Breathing frequency (f) and tidal volume (VT) of unanesthetized, unrestrained mice were assessed by whole body plethysmography. During room air breathing, significant (P < 0.01) interstrain differences were noted in the pattern, but minute ventilation (VE) did not differ among the strains. Relative to room air, mild hypercapnia with hypoxia (0.03:0.10) significantly (P < 0.01) elevated VE in each strain, and the percent increase in VE of the DBA/2J strain was significantly (P < 0.05) greater than the other strains. The ventilatory response to these conditions was achieved primarily by a significant (P < 0.01) increase in f among the strains. During severely hypercapnic normoxia (0.08:0.21) and hypoxia (0.08:0.10), the increase in VE was significantly (P < 0.01) greatest in the C57BL/6J (B6) mice and least in the C3H/HeJ (C3) mice. The difference in hypercapnic VE between B6 and C3 strains was largely due to a significantly (P < 0.01) greater increase in VT by B6 mice. On the assumption that environmental factors were identical, these data suggest that genetic determinants govern interstrain variation in the magnitude and pattern of breathing during hypoxia and hypercapnia. Moreover, hypoxic and hypercapnic ventilatory responses appear to be influenced by different genetic mechanisms.
Temperature gradient osmometer and anomalies in freezing temperatures
Authors: Arav A. , Rubinsky B.
Published: December 2017

We have developed a new device that measures freezing and melting temperatures in nanoliter volume samples and can be used as a "freezing point osmometer" with a resolution many orders of magnitude greater than that of existing freezing point osmometers. Using this device we found anomalies in the depression of the freezing temperature and thermal hysteresis in aqueous solutions of hydrophilic amino acids, polyamino acids, and lectins. These anomalies would not have been possible to detect with currently used technology. The compounds that produce anomalies in freezing temperature were reported in the literature as having the ability to bind to cell membranes. This suggests a relation between a molecule's ability to bind to cell membranes and its anomalous freezing temperature depression. The new freezing point osmometer and our results could be important for studying and understanding organic molecules and their interaction with membranes and water.
Increased renal nerve activity in cardiac failure: arterial vs. cardiac baroreflex impairment
Authors: DiBona G. F. , Sawin L. L.
Published: December 2017

Cardiac failure is characterized by increased renal sympathetic nerve activity that is associated with an impairment of both arterial and cardiac baroreceptor reflex function. These reflex dysfunctions are in the afferent limb at the level of the peripheral baroreceptors. This study sought to define the relative quantitative magnitude of the defects in arterial and cardiac baroreceptor function in cardiac failure. Renal sympathetic nerve activity was measured in anesthetized normal control rats and rats with cardiac failure (left coronary ligation) during sequential random order sinoaortic denervation and vagotomy to interrupt afferent input from the arterial and cardiac baroreceptors, respectively. Increases in renal sympathetic nerve activity after individual or combined sinoaortic denervation and vagotomy were less (P < 0.05 for both) in cardiac failure than in normal control rats in both order sequences (42 +/- 5 vs. 87 +/- 8%; 44 +/- 5 vs. 108 +/- 7%). In cardiac failure rats, vagotomy produced lesser increases (P < 0.05 for both) in renal sympathetic nerve activity than sinoaortic denervation in both order sequences (10 +/- 4 vs. 32 +/- 5%; 13 +/- 2 vs. 30 +/- 5%). The relative magnitude of impaired cardiac baroreceptor reflex function that is associated with the increased renal sympathetic nerve activity of cardiac failure is greater than that of impaired arterial baroreceptor reflex function.
Gut-brain signaling of water absorption inhibits vasopressin in rats
Authors: Baertschi A. J. , Pence R. A.
Published: December 2017

The mechanism for inhibition of vasopressin (AVP) by gastric water infusion was examined in 24- or 48-h dehydrated conscious rats (n = 136 rats, 255 experiments; mean AVP baseline = 6.3 pg/ml). Gastric water infusions of 1 (n = 8), 2.5 (n = 19), and 4 ml (n = 10) caused a volume-dependent inhibition of plasma AVP by -0.31, -1.77*, and -3.02* pg/ml, with decreases of systemic osmolality of -1.06, -1.52, and -4.26* mosmol/kgH2O (* = significant vs. isotonic, Duncan's test). Gastric isotonic infusions (1-4 ml) had no effect or slightly increased AVP. Systemic infusions of 1.25 (n = 6), 2.1 (n = 10), and 6.3 ml (n = 8) inhibited AVP by -0.48, -1.07, and -2.51 pg/ml, with decreases in systemic osmolality of -1.61, -2.77*, and -7.21* mosmol/kgH2O. Systemic isotonic infusions (2.1 and 6.3 ml) slightly inhibited AVP by -0.71 and -0.85 pg/ml. Individual changes in AVP by gastric infusion of 2.5 ml of water did not correlate with changes in systemic osmolality, mean arterial pressure, or heart rate but highly correlated with preinfusion AVP (r = 0.74, P < 0.0001, n = 28). Pretreatment with systemic atropine methyl bromate (0.7 mg/rat), which abolishes the AVP secretion to gastric hypertonic saline, did not affect the AVP response to gastric water infusion (n = 9). Combination of 2.5 ml of gastric water and systemic hypertonic saline prevented the decrease in systemic osmolality and still significantly inhibited plasma AVP. Maximal inhibition of AVP by gastric water was reduced by 62.6% after lesion of the common hepatic vagal branch (n = 5) relative to shams with identical abdominal surgery (n = 6) and by 62.7 and 72.5% after right (n = 11) and left (n = 8) cervical vagotomy relative to 12 shams (P < 0.05). The results show that 1) gastric water absorption is signaled mainly by splanchnic osmosensors, 2) water signaling is atropine insensitive, and 3) the major water-signaling pathway projects through the common hepatic vagal branch and cervical vagal nerves.
Naloxone blocks that portion of feeding driven by sweet taste in food-restricted rats
Authors: Levine A. S. , Weldon D. T. , Grace M. , Cleary J. P. , Billington C. J.
Published: December 2017

We evaluated the potency of naloxone on intake of normal and sweet chow in food-deprived and schedule-fed rats. We found that naloxone's anorectic potency was dependent on the type of chow presented to the rats and the deprivation schedule utilized to stimulate food intake. In 24-h and 48-h deprived rats, naloxone decreased intake of normal rat chow at doses ranging from 0.3 to 3 mg/kg. In chronically deprived rats (80% of normal body wt), these doses of naloxone failed to decrease intake of normal chow. Rats eating sweet chow ate more when energy deprived and were more sensitive than rats eating normal chow to naloxone-induced limitations in food intake, both in acute and chronic food-deprived groups. Thus naloxone decreased intake of sweet chow much more effectively than normal chow even when rats were chronically food deprived. We also found that an extremely low dose of naloxone (0.03 mg/kg) decreased intake of sweet chow by almost 50% in satiated rats.
Cytokines and the acute phase response to influenza virus in mice
Authors: Conn C. A. , McClellan J. L. , Maassab H. F. , Smitka C. W. , Majde J. A. , Kluger M. J.
Published: December 2017

This study characterized selected aspects of the acute phase response after intranasal inoculation of mice with two doses of mouse-adapted influenza virus differing in lethality. Mice given 140 plaque-forming units (PFU) of virus (58% survival) gradually decreased food and water intake to nearly zero over 6 days; survivors then slowly increased intakes. Declines in these behaviors were parallel to decreases in body temperature and general locomotor activity and were associated with elevated activities of interleukin-6 (IL-6), tumor necrosis factor-alpha, and interferons in lung lavage fluid. Circulating levels of these cytokines were not increased. After 55,000 PFU of virus (100% mortality), food and water intake fell to near zero within 48 h, temperature and locomotor activity decreased significantly, and activities of IL-1 and IL-6 were elevated in lung lavage fluid. These data show that cytokine activities in the lungs are elevated in a time frame that supports the hypothesis that cytokines could mediate behavioral and physiological changes in mice during acute influenza infections.
Fetal responses to carotid occlusion: immaturity of buffering systems
Authors: Wood C. E.
Published: December 2017

In postnatal animals, carotid occlusion does not stimulate reflex hormonal responses, because decreases in carotid arterial baroreceptor activity are balanced by reflex-mediated increases in vagal afferent traffic from aortic and cardiac receptors. The present experiments were designed to test the hypothesis that hormonal responses to carotid occlusion in fetal animals are not inhibited by vagal afferents. In thirteen chronically catheterized fetal sheep (125-146 days), bilateral carotid occlusion (n = 11) increased arterial blood pressure from 44.0 +/- 2.4 to 55.2 +/- 3.3 mmHg, decreased heart rate from 189 +/- 5 to 165 +/- 12 beats/min, increased plasma adrenocorticotropin from 71 +/- 15 to 248 +/- 79 pg/ml and vasopressin from 3.0 +/- 1.0 to 7.4 +/- 2.6 pg/ml but did not significantly alter renin. Plasma hormone concentrations were not significantly altered in control (n = 7) experiments or in response to unilateral carotid occlusion (n = 4). The results of these experiments demonstrate the functional immaturity of the vagal afferent buffering systems in the late-gestation fetus compared with the postnatal animal.
Rates of glucose utilization in brain of active and hibernating ground squirrels
Authors: Frerichs K. U. , Dienel G. A. , Cruz N. F. , Sokoloff L. , Hallenbeck J. M.
Published: December 2017

Rates of glucose utilization (CMRGlc) were determined in some cerebral structures of active warm- and cold-adapted ground squirrels and hibernating ground squirrels with [14C]deoxyglucose (DG) by direct chemical measurement of precursor and products in samples dissected from funnel-frozen brain. The rate of supply relative to demand of glucose and [14C]DG in brain of hibernating animals was similar to or greater than that of controls. [14C]DG cleared from the plasma in hibernators much more slowly than in active animals, and the level of unmetabolized [14C]DG in brain and the integrated specific activity of the precursor pool in plasma exceeded those of the active animals by 4- to 10-fold. At 45 min after an intravenous pulse of [14C]DG, the unmetabolized [14C]DG remaining in the brains of the hibernators accounted for approximately 96% of the total 14C compared with approximately 10-15% in the active animals. The value of lambda, a factor contained in the lumped constant of the operational equation of the [14C]DG method, was estimated for each animal and found to be relatively constant over the sixfold range of glucose levels in the brains of all animals. Calculated CMRGlc in squirrels in deep hibernation was only 1-2% of the values in active animals.
Intracellular Ca2+ transients evoked by lactic acid in cultured mammalian neurons
Authors: Nedergaard M.
Published: December 2017

During cerebral ischemia, accumulation of the glycolytic end product lactic acid may contribute to brain infarction. In vitro, lactic acid evokes a process of slowly evolving neuronal death characterized by a transient maintenance of cellular viability after initial injury. We examined effects of lactic acid on intracellular Ca2+ (Cai2+). Cultured neurons loaded with the fluorescent Ca2+ indicator fura 2 showed a marked increase in Cai2+ to as high as 600 nM. This increase occurred after lactic acid exposure when intracellular pH had normalized. Membrane potential was unaltered during this period, indicating that the Cai2+ increment was not a result of membrane depolarization. Increase in Ca2+ was prevented by incubating cultures in Ca(2+)-free solutions or exposing them to the L-type Ca2+ channel antagonist nimodipine. Cai2+ returned to resting levels within 20 min and remained normal during the remainder of the 4-h observation period. Neuronal Ca2+ homeostasis was disrupted after lethal exposure to lactic acid, in that subsequent exposure to 50 mM K+ failed to increase neuronal Cai2+. Cai2+ increment was integrated over a 20-min period to obtain a measure of neuronal Cai2+ load. This “calcium integral” was found to correlate directly with severity of neuronal damage observed 24 h later. Thus the Cai2+ increase integrated over time closely reflected the likelihood of lethal neuronal injury after lactic acid exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of electrogenic Na+ transport across leech skin
Authors: Weber W. M. , Blank U. , Clauss W.
Published: December 2017

The dorsal integument of the medical leech Hirudo medicinalis exhibits a marked amiloride-sensitive Na+ absorption. With 20 mM Na+ in the apical solution, the transepithelial short-circuit current (Isc) was approximately 40% higher than with 115 mM Na+, whereas the transepithelial potential (VT) with 20 mM Na+ was -35.7 +/- 4.5 and -20.6 +/- 2.6 mV with 115 mM Na+. Amiloride (100 microM) inhibition at 20 mM apical Na+ was also significantly larger than with 115 mM Na+ in the solution. Benzamil (100 microM) showed additional inhibition after amiloride. Large transient overshooting currents occurred only when 115 mM Na+ was added after some minutes of Na(+)-free apical solution. Addition of adenosine 3',5'-cyclic monophosphate (cAMP) to the serosal side in the presence of 115 mM apical Na+ nearly doubled Isc. This cAMP effect was reduced to only 20% in the presence of 20 mM Na+. Guanosine 3',5'-cyclic monophosphate (cGMP) slightly increased Isc, whereas ATP showed biphasic potency. Removal of calcium from the apical side resulted in a large stimulation of amiloride-sensitive Isc only in the presence of 115 mM Na+. When currents were activated with cAMP, a deprivation of Ca2+ modestly reduced the amiloride-sensitive Isc. The Na+ channel of leech integument was found highly selective for Na+ over other monovalent cations. The permeability ratio for Na+ over K+ was approximately 30:1; the selectivity relationship for the investigated cations was Na+ > Li+ > NH4+ > K+ approximately Cs+ approximately Rb+.
Sex hormone modulation of flow velocity in the parametrial artery of the pregnant rat
Authors: Gorodeski G. I. , Sheean L. A. , Utian W. H.
Published: December 2017

The objective of the study was to correlate the disparate distal/proximal state of maturation of uterine segments in the rat with the hemodynamics of the parametrial uterine artery. Flow velocity was determined by the methylene blue photometric analysis. In nonpregnant animals, the velocity in the distal (VD-->P) and proximal (VP-->D) portions of the parametrial artery were similar, but in late pregnancy, VD-->P was higher than VP-->D. The difference was associated with an increased width of the distal part of the parametrial artery. In addition, the distance from the proximal end of the parametrial artery where the D-->P and P-->D streams collided decreased in animals in late pregnancy, compared with nonpregnant animals. Treatment with estradiol and RU-486 reversed the pregnancy-related hemodynamic changes. The pregnancy-related shift in flow velocity in the parametrial artery is crucial to rat fetal survival in utero and may be a mechanism in vivo for promoting maturation of distal, compared with proximal, segments of the uterine horn.
Paraventricular nucleus neurons projecting to the spinal cord receive excitatory input from the subfornical organ
Authors: Bains J. S. , Ferguson A. V.
Published: December 2017

The present study utilized electrophysiological techniques to determine the effects of subfornical organ (SFO) stimulation on the activity of neurons in the paraventricular nucleus (PVN) projecting to the spinal cord. Single-unit recordings were obtained from 79 PVN neurons antidromically identified as projecting to the intermediolateral cell column (IML). Antidromically evoked action potentials showed a mean latency of 94.6 +/- 5.3 ms and a mean threshold for activation of 1.58 +/- 0.11 mA. Electrical stimulation of SFO (100 microA-1.5 mA, 0.1 ms) resulted in excitatory responses in 18 of the 27 neurons tested (67%). Peristimulus histogram analysis of such effects demonstrated a duration of < 50 ms in 14 of the 18 cells so influenced (78%), whereas the remaining 4 cells (22%) showed excitatory responses with a longer duration. Systemic administration of the nonpeptidergic angiotensin II (ANG) type 1 (AT1) receptor antagonist losartan (3 mg/kg) blocked the long-duration excitatory responses in 100% (3 of 3) of the cells tested but was without effect on the short-duration excitations (0 of 5). Twenty-two identified PVN neurons were also tested for their responses to systemic ANG (20-500 ng), which had no observable effect on the activity of any of these cells. These data demonstrate that neurons in SFO provide excitatory input to PVN cells that project to the IML. One of the neurotransmitters responsible for communication in this pathway is ANG.
Peripheral chemoreceptor inputs to the parabrachial nucleus of the rat
Authors: Hayward L. F. , Felder R. B.
Published: December 2017

In the urethan-anesthetized rat, extracellular recordings were made from 60 neurons within the region of the parabrachial nucleus (PBN). The activity of 37 of 44 neurons was altered by selective stimulation of peripheral chemoreceptors via intracarotid injection of NaH2PO4 or CO2-saturated NaHCO3. Most of these neurons (28 of 37) were excited during chemoreceptor stimulation. Twenty-four of 48 neurons responded to changes in baroreceptor input via changes in blood pressure. Most of these neurons (18 of 24) were inhibited during baroreceptor stimulation. Eleven of 32 neurons were affected by both chemoreceptor and baroreceptor inputs. Seven of these neurons had opposite responses during selective afferent stimulation; that is, they were excited during chemoreceptor activation and inhibited during baroreceptor activation. Our observations reveal that neurons within the medial and lateral PBN are responsive to peripheral chemoreceptor input. A subgroup of PBN neurons was shown to integrate information from chemoreceptors and baroreceptors. These results suggest that both the medial and lateral PBN may play a role in the central integration of cardiovascular inputs.
Cuneiform nucleus stimulation produces activation of medullary sympathoexcitatory neurons in rats
Authors: Verberne A. J.
Published: December 2017

Activation of the cuneiform nucleus (CNF) of the midbrain produces elevation of arterial blood pressure. This study examined the influence of the CNF on arterial blood pressure, sympathetic vasomotor outflow, and the discharges of barosensitive sympathoexcitatory neurons of the rostral ventrolateral medulla (RVLM) in halothane-anesthetized, paralyzed rats. Electrical stimulation (50 Hz, 25-75 microA, 10 s) of the CNF elicited intensity-dependent elevations in arterial blood pressure associated with excitation of the sympathetic vasomotor discharge (elevated discharge of the lumbar sympathetic nerve). Intermittent paired-pulse electrical stimulation of the CNF elicited an excitatory response in the discharge of the lumbar sympathetic outflow that consisted of an early peak (onset latency 84 +/- 4 ms) and a smaller late peak (onset latency 217 +/- 6 ms). Seventeen of 22 RVLM sympathoexcitatory neurons tested were excited by stimulation of the CNF. Twelve of 14 units tested projected to the thoracic spinal cord, and of these, 10 units were excited by CNF stimulation with an onset latency of 16 +/- 1 ms. These findings support the hypothesis that the sympathoexcitatory and pressor responses elicited by activation of the CNF are mediated by RVLM sympathoexcitatory neurons.
Ion transport in gills of the euryhaline fish Gillichthys mirabilis is facilitated by a phosphocreatine circuit
Authors: Kultz D. , Somero G. N.
Published: December 2017

The function of creatine kinase (CK) isozymes in energy metabolism and the short-term regulation of active ion transport in gills of the euryhaline teleost Gillichthys mirabilis was investigated. After a transfer of fish from regular seawater [36 parts/thousand (ppt)] to hypersaline water (60 ppt), the plasma osmolality increased significantly from 361.0 +/- 5.2 to 434.2 +/- 20.6 mosmol/kgH2O within 2 h and was regulated down to 391.8 +/- 11.3 mosmol/kgH2O within 12 h. Although the ATP concentration in the gill tissue remained unchanged, the creatine concentration increased significantly from 17.3 +/- 3.2 to 37.6 +/- 5.9 nmol/mg protein within 2 h after the salinity change. CK and Na(+)-K(+)-adenosinetriphosphatase-(Na(+)-K(+)-ATPase) activities were unchanged 48 h after transfer. Independent of salinity, the activities of CK were three to seven times those of the Na(+)-K(+)-ATPase, and the creatine concentration in the gill was at least one order of magnitude higher than the ATP concentration. The occurrence of muscle-type CK (CK-M), brain-type CK, and mitochondrial CK was demonstrated. CK-M was predominant in gills (59 +/- 7.1% of total CK activity). Evidence for a direct functional coupling between CK and Na(+)-K(+)-ATPase was obtained with permeabilized gill cells, by using the CK inhibitor iodoacetamide, which abolishes the competitive channeling of ADP from the external pyruvate kinase reaction to the endogeneous CK reaction in a coupled in situ Na(+)-K(+)-ATPase assay. Our results show the significance and the central regulatory role for energy metabolism and adaptive ionoregulation of a phosphocreatine-CK circuit in situations of high and fluctuating energy demands for euryhaline fishes.