bluuebunny/crossref_metadata_2025 huggingface dataset:
Rates of local cerebral protein synthesis in the rat during normal postnatal development
Authors: Sun Y. , Deibler G. E. , Jehle J. , Macedonia J. , Dumont I. , Dang T. , Smith C. B.
Published: December 2017

The degree of recycling of leucine derived from protein breakdown into the precursor pool for protein synthesis was measured in rat brain at different postnatal ages, and age-specific values were used in the calculation of regional (local) rates of cerebral leucine incorporation into protein (lCPSleu) in 44 brain regions and the brain as a whole. Early in development, a greater fraction of the precursor leucine pool is derived from protein breakdown, indicating that protein degradation is higher in young rats compared with adults. In whole brain and in most regions, values for lCPSleu were highest at 10 days and gradually decreased with age. By 60 days of age, values in cortex were approximately 60% of those at 10 days of age. In the paraventricular and supraoptic nuclei of the hypothalamus, however, lCPSleu increased during development, reaching peak values in adults. In white matter of the cerebellum and the cerebrum, peaks of lCPSleu were reached at 14 and 21 days, respectively, approximately at the times of maximum rates of myelination.
Effects of input pressure on in vitro turtle heart during anoxia and acidosis: a 31P-NMR study
Authors: Jackson D. C. , Shi H. , Singer J. H. , Hamm P. H. , Lawler R. G.
Published: December 2017

In vitro working hearts of the turtle, Chrysemys picta bellii, paced at 30 beats/min, were studied over a range of input pressures in the following sequence of perfusion conditions: control normoxia, control anoxia, lactacidotic normoxia, and lactacidotic anoxia. Two such series of experiments were performed. In series 1 (n = 12), ventricular pressure (PV) and cardiac output were measured, and power output and dPV/dt were calculated. In series 2 (n = 5), intracellular phosphorus metabolites and intracellular pH (pHi) were also measured using 31P-nuclear magnetic resonance (31P-NMR) spectroscopy. In series 1 all mechanical variables increased with input pressure in generally similar fashion, except during anoxic acidosis, during which mechanical performance was depressed and was increased less or not at all by input pressure. Creatine phosphate (CP) and pHi fell significantly in anoxia and anoxic acidosis, but neither these variables, ATP, CP/ATP, nor, presumably, ADP changed as a function of input pressure with any perfusate despite often large increments in mechanical output. We conclude that anoxia and acidosis act synergistically to depress cardiac function in turtle hearts. Also, the insensitivity of NMR variables to changes in input pressure and cardiodynamics suggests that changes in these variables are unimportant for controlling energy turnover in this preparation.
Neurochemical interactions in the parabrachial nucleus mediating visceral inputs to visceral thalamic neurons
Authors: Saleh T. M. , Cechetto D. F.
Published: December 2017

Previously we demonstrated that glutamatergic and noradrenergic receptors mediate the relay of visceral information through the parabrachial nucleus (PBN) and that calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), neurotensin (NT), and cholecystokinin (CCK) may modulate these responses. The interactions of these neurotransmitters and neuropeptides were examined in male Wistar rats (17) that were anesthetized with chloral hydrate and ventilated and in which blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated at submaximal current intensities to elicit changes in single and multiunit activity of visceral thalamic neurons (VTNs). Peristimulus-time and continuous-time histograms of VTN activity were made before and after 200-nl injections of peptides, neurotransmitter agonists or antagonists, or artificial cerebrospinal fluid into the PBN. Combined injection of CGRP and SP into the PBN produced a synergistic inhibition of spontaneous VTN activity and the vagally evoked VTN response. Combined injection of NT and phenylephrine (PE) into the PBN produced only an additive increase in the spontaneous activity of VTNs. Prior administration of SOM in the PBN blocked the excitatory action of an alpha-adrenergic agonist (phenylephrine) injection on the spontaneous activity of VTNs, whereas CGRP, SP, or CCK had no effect on the alpha-agonist-induced response. Prior injection of an alpha-adrenergic antagonist (phentolamine) prevented the excitatory effect of NT in the PBN. Injection of CGRP, SP, NT, or CCK into the PBN did not change the response of VTNs to application of glutamate. These results suggest mechanisms for peptide interaction with primary neurotransmitters in the PBN and indicate whether the neuropeptides are acting before the primary neurotransmitter synapse or postsynaptically.
Opioid growth factor modulates corneal epithelial outgrowth in tissue culture
Authors: Zagon I. S. , Sassani J. W. , McLaughlin P. J.
Published: December 2017

In addition to neuromodulation, endogenous opioid peptides serve as growth factors. To determine involvement of opioids in the homeostatic renewal and repair of the corneal epithelium, epithelial outgrowths from 3-mm explants of rabbit cornea were investigated. Blockade of opioid-receptor interaction by the potent opioid antagonist naltrexone (NTX) for 7 days significantly increased the extent of outgrowths and the number and labeling index (DNA synthesis) of epithelial cells, relative to control levels. Outgrowths exposed to the opioid growth factor (OGF) [Met5]enkephalin for 7 days were subnormal in extent and labeling index and displayed alterations in architectural pattern. The effects of OGF on epithelial outgrowth were blocked by concomitant exposure to the opioid antagonist naloxone; naloxone alone had no effect on growth at the concentration utilized. NTX and OGF were active in both serum-containing and serum-free cultures. Immunocytochemical investigations showed that both OGF and its opioid receptor zeta (zeta) were present in epithelial cells growing in control media. The results indicate that an endogenous opioid peptide and its receptor are present in mammalian corneal epithelium and serve to modulate cell proliferation, migration, and organization.
Lactate influx into red blood cells of athletic and nonathletic species
Authors: Skelton M. S. , Kremer D. E. , Smith E. W. , Gladden L. B.
Published: December 2017

Transport of lactate across the erythrocyte membrane proceeds by three distinct pathways: 1) nonionic diffusion of lactic acid, 2) inorganic anion exchange (band 3), and 3) a monocarboxylate-specific (MC) carrier mechanism. This study determined the contributions of these three pathways in the red blood cells (RBCs) of “athletic” and “nonathletic” species. Blood samples were obtained from four male animals of each species: 1) Canis familiaris (dogs), 2) Capra hircus (goats), 3) Equus caballus (horses), and 4) Bos taurus (cattle). Contribution of each pathway to total lactate influx was determined by measuring L-[14C]lactate influx into lactate-depleted control RBCs, p-chloromercuribenzenesulfonic acid (PCMBS)-treated (1 mM) RBCs, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-treated (0.2 mM) RBCs at three lactate concentrations ([La] values 1.6, 8.1, and 41 mM). PCMBS blocked MC transport and DIDS blocked the band 3 pathway. Lactate influx into the RBCs of the athletic species was 4-160 times faster (P < 0.05) than influx into the RBCs of the nonathletic species at 8.1 and 41 mM [La] values. Nonionic diffusion was greater in the RBCs of nonathletic animals (approximately 7-25%) than in the RBCs of athletic animals (approximately 4%). A significantly higher percentage of the total lactate influx occurred via the band 3 system in the RBCs from the nonathletic animals (approximately 56-83%) vs. the RBCs from the athletic animals (approximately 6-7%) at all [La] values.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinetic studies and production rate of melatonin in pony mares
Authors: Guillaume D. , Rio N. , Toutain P. L.
Published: December 2017

The aims of the present study were to determine basic kinetic parameters and the nycthemeral production rate of melatonin in the horse. Seven pony mares were used for the kinetic studies. Five other pony mares were used under long and short days for the production rate studies. Melatonin was administered by intravenous, oral, and intragastric routes at different dose levels. The plasma melatonin clearance was 1.02 +/- 0.31 l.kg-1.h-1, and the volume of distribution was 0.89 +/- 0.53 l/kg for the 0.4 microgram/kg melatonin dose. The systemic availability after oral and intragastric administration was consistently low (< or = 10%). The hourly melatonin production rates during short (36 +/- 33.6 ng.kg-1.h-1) and long nights (42 +/- 24.0 ng.kg-1.h-1) were not significantly different. It is concluded that the oral dose of exogenous melatonin required to control reproductive pattern in horses would need to be 10 times higher than the nocturnal melatonin production (0.5 microgram/kg) to obtain a physiological plasma melatonin concentration.
Lipopolysaccharide increases EEG delta activity within non-REM sleep and disrupts sleep continuity in rats
Authors: Lancel M. , Cronlein J. , Muller-Preuss P. , Holsboer F.
Published: December 2017

Activation of the immune system by microorganisms or specific microbial constituents promotes non-rapid-eye-movement (REM) sleep (non-REMS). In this study, we assessed the effects of lipopolysaccharide (LPS) on sleep duration, electroencephalogram (EEG) power spectra, and brain temperature (Tbr) in rats. Twenty-four hour recordings were made before and after intraperitoneal injection of vehicle or 30 or 100 micrograms/kg LPS at lights on. During the first 12 h after administration of both doses of LPS, Tbr was elevated, REMS duration was reduced, and non-REMS duration was unchanged, whereas the non-REMS episodes were shortened. EEG activity within non-REMS from 0.5 to 7 Hz was enhanced during hours 3-12. During the second 12-h period, the number of non-REMS and REMS episodes and the total time in both states were increased. EEG activity within non-REMS was mainly reduced in the entire frequency range (0.5-25.5 Hz). The effects of LPS did not differ between the doses. The effects of LPS on EEG power spectra are similar to those observed after sleep deprivation, i.e., a physiological intensification of non-REMS, indicating that both manipulations may activate common sleep EEG regulatory mechanisms. However, the disruption of non-REMS continuity following LPS administration at light onset contrasts the changes induced by sleep deprivation and may reflect an effect of a systemic inflammatory response on sleep maintenance.
Rat vasopressin cell responses to simulated hemorrhage: stimulus-dependent role for A1 noradrenergic neurons
Authors: Smith D. W. , Sibbald J. R. , Khanna S. , Day T. A.
Published: December 2017

c-fos expression mapping and electrophysiological recording experiments were done to clarify the role of the A1 noradrenergic cell group in the vasopressin response to hypotensive hemorrhage. In pentobarbital-anesthetized rats, moderate and severe hypotensive hemorrhages were simulated by brief occlusion of the inferior vena cava sufficient to reduce mean arterial pressure to approximately 50 or 30 mmHg, respectively. Both stimuli significantly increased the number of A1 region catecholamine cells displaying Fos-like immunoreactivity, this effect being most prominent at the level of the area postrema. Both stimuli also increased the number of supraoptic nucleus vasopressin cells displaying Fos-like immunoreactivity. Accordingly, electrophysiological studies involving separate animals confirmed that both moderate and severe caval occlusion significantly increased the firing of functionally identified vasopressin cells recorded in the supraoptic nucleus. However, although interruption of A1 region neuronal function by injection of gamma-aminobutyric acid at the level of the area postrema eliminated the increase in vasopressin cell firing elicited by moderate caval occlusion, it did not block the response to severe caval occlusion. These findings suggest that, in the rat, the vasopressin response to an acute reduction in central blood volume, such as that produced by hemorrhage, depends on the A1 projection only if the stimulus is of moderate intensity. Severe stimuli appear to involve activation of both the A1 projection and an additional vasopressin-stimulatory pathway that bypasses the A1 region.
Enterohepatic circulation kinetics of bile-active folate derivatives and folate homeostasis in rats
Authors: Shin H. C. , Takakuwa F. , Shimoda M. , Kokue E.
Published: December 2017

We examined the effect of enteric infusion of 5,10-methylenetetrahydrofolate (5,10-CH2-H4PteGlu), tetrahydrofolate (H4PteGlu), 10-formyltetrahydrofolate (10-HCO-H4PteGlu), and 5-methyltetrahydrofolate (5-CH3-H4PteGlu) on concentrations of plasma 5-CH3-H4PteGlu in rats. Concentrations of plasma 5-CH3-H4PteGlu rapidly decreased during continuous bile diversion, whereas initial levels of plasma 5-CH3-H4PteGlu were maintained by means of enteric infusion of 5-CH3-H4PteGlu at a dose of 3 nmol/h, which was approximately equal to total secretion of bile folates. Plasma 5-CH3-H4PteGlu levels were also maintained by the infusion of 5,10-CH2-H4PteGlu, H4PteGlu, or 10-HCO-H4PteGlu at the same dose as 5-CH3-H4PteGlu. The results indicate that folates secreted into the bile are reabsorbed through the intestine to regulate plasma concentrations of 5-CH3-H4PteGlu. We examined the secretion kinetics of bile folates after the intravenous injection of 5-CH3-H4PteGlu or folic acid (PteGlu) at 1 mg/kg body wt. When 5-CH3-H4PteGlu was injected, the bile secretion of folates other than 5-CH3-H4PteGlu increased by < 5 times the base level, whereas that of bile 5-CH3-H4PteGlu markedly increased by approximately 30 times. When PteGlu was given, the bile secretion of nonmethylated tetrahydrofolates markedly increased by 15-27 times, whereas that of 5-CH3-H4PteGlu increased by approximately 7 times. The results suggest that oxidized folates may be one of the sources for bile nonmethylated tetrahydrofolates. It is concluded that nonmethylated tetrahydrofolates in bile play an important role in folate homeostasis through enterohepatic circulation, together with 5-CH3-H4PteGlu.
Varying photoperiod in the laboratory rat: profound effect on 24-h sleep pattern but no effect on sleep homeostasis
Authors: Franken P. , Tobler I. , Borbely A. A.
Published: December 2017

To assess the influence of the photoperiod on sleep regulation, laboratory rats were adapted to a long photoperiod (LPP; 16:8-h light-dark cycle, LD 16:8) or a short photoperiod (SPP; LD 8:16). The electroencephalogram (EEG) and cortical temperature (TCRT) were continuously recorded for a baseline day, a 24-h sleep deprivation (SD) period, and a recovery day. Data obtained previously for LD 12:12 served for comparison. Whereas the photoperiod exerted a prominent effect on the 24-h sleep pattern, the 24-h baseline level of sleep and the response to SD were little affected. Recovery from SD was characterized by a marked rise in rapid eye movement sleep, a moderate rise in non-rapid eye movement sleep, and an initial enhancement of EEG slow-wave activity followed by a decrease below baseline. The amplitude and phase of the "unmasked" 24-h component of TCRT did not differ between LPP and SPP. Computer simulations demonstrated that the changes of TCRT and EEG slow-wave activity can be largely accounted for by the sequence of the vigilance states. We conclude that the photoperiod does not affect the basic processes underlying sleep regulation.
Effect of thyroid hormone replacement in iron-deficient rats
Authors: Brigham D. E. , Beard J. L.
Published: December 2017

To determine if the previously observed alterations in norepinephrine (NE) metabolism and resting metabolic rate in iron-deficient (ID) rats result from hypothyroidism, exogenous thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were administered to ID rats in doses sufficient to normalize the plasma concentrations of these hormones, whereas other ID and control (CN) rats received placebo treatment. Resting oxygen consumption was approximately 25% higher in ID than CN rats; T4 but not T3 treatment alleviated this elevated oxygen uptake. The NE content of interscapular brown adipose tissue (IBAT), liver, and heart was 70-80% lower in ID than CN rats, and NE turnover in the same tissues was likewise 40-60% lower in ID than CN rats, with no systematic effect of either T3 or T4 treatment. Liver T(4)5'-deiodinase activity was 70% lower in ID than CN rats and increased with T4 but not T3 treatment. These experiments show that iron deficiency alters NE and energy metabolism in a way that is mostly independent of its effects on thyroid hormone metabolism.
Changes in efferent pulmonary sympathetic nerve activity during systemic hypoxia in anesthetized cats
Authors: Shirai M. , Matsukawa K. , Nishiura N. , Kawaguchi A. T. , Ninomiya I.
Published: December 2017

Changes in efferent sympathetic nerve activity to the pulmonary vessels during systemic hypoxia have yet to be elucidated. The purpose of this study was to determine the pulmonary sympathetic nerve activity (PSNA) changes in response to acute systemic hypoxia before and after sinoaortic denervation plus vagotomy in anesthetized cats. The denervation was performed to estimate the central nervous system-mediated peripheral chemoreceptor- and baroreceptor-independent PSNA change. PSNA was recorded from the central end of the cut nerve bundle, which was isolated from the lobar artery supplying the diaphragmatic lobe. Renal sympathetic nerve activity (RSNA) and systemic and pulmonary arterial pressures were also measured simultaneously. The animals were submitted to approximately 3-min periods of graded hypoxia (16, 12, 8, 5, and 3% O2 inhalations). PSNA did not change from normoxia down to an arterial O2 partial pressure (PaO2) of approximately 45 Torr (with 12-21% O2 inhalations). Below this level, PSNA began to increase, and markedly so (approximately 2.5-fold) at a PaO2 of approximately 15 Torr (with 3% O2). The hypoxic PSNA increase was significantly larger than that for RSNA, with a PaO2 of less than approximately 30 Torr (with 3-8% O2). Particularly at a PaO2 of approximately 15 Torr, the magnitude of the PSNA increase was two times greater than that for RSNA. After denervation, the hypoxic PSNA increase was significantly attenuated at a PaO2 of approximately 25 to approximately 45 Torr (with 5-12% O2), but the attenuation was very small; therefore most of the PSNA increase persisted. The hypoxic RSNA increase, in contrast, was mostly abolished after denervation. The data indicate that the neural reflex effect of systemic hypoxia on PSNA is significantly greater than that on RSNA and suggest that the hypoxic PSNA increase is mostly mediated by central mechanisms, whereas that for RSNA is chiefly caused by peripheral chemoreceptors.
Regeneration and revascularization of a nerve-intact skeletal muscle graft in the spontaneously hypertensive rat
Authors: Carlsen R. C. , Kerlin D. , Gray S. D.
Published: December 2017

Skeletal muscles in hypertensive subjects develop an increased resistance to insulin that reduces their ability to incorporate glucose and synthesize glycogen. Insulin is an anabolic hormone in muscle, and muscle insulin receptors bind the growth factor, insulin-like growth factor I (IGF-I), an important contributor to muscle development and regeneration. An increase in insulin resistance in hypertensive subjects might produce muscle atrophy and weakness or limit regenerative growth after injury. Regenerative muscle growth was assessed in 24-to 26-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats by subjecting extensor digitorum longus (EDL), an ankle flexor, to a nerve-intact graft procedure. The procedure produces extensive muscle fiber and capillary degeneration, but has little effect on the muscle nerve. Muscle morphology and contractile function were examined in intact and regenerating EDL at 21, 42, and 63 days postgraft. Muscle revascularization was assessed histologically at the same time points. Severe established hypertension did not prevent the reestablishment of a structurally normal capillary network in injured muscles. SHR muscle fiber regeneration and maturation, however, were significantly depressed compared with WKY grafts. The reduced regenerative recovery of SHR EDL in adult animals with severe hypertension does not appear to be due to a failure to restore the muscle nerve or capillary network, but may reflect a reduced anabolic response to insulin or IGF-I.
Alteration of plasma folates in gestating sows and newborn piglets
Authors: Natsuhori M. , Shimoda M. , Kokue E.
Published: December 2017

Plasma folates tetrahydrofolate (THF) and N5-methyltetrahydrofolate (5MF) were determined in nongestating, gestating, and lactating sows (2 to 4 yr old, 2-6 parities, n = 88) and in newborn, growing, and finishing pigs (0 to 158 days old, n = 191) with the use of high-performance liquid chromatography with an electrochemical detector. Plasma folates after folic acid injection (1 mg/kg iv) were also monitored in 2-day-, 2-wk-, and 2-mo-old pigs. In sows, plasma folates decreased significantly as pregnancy advanced. This was mainly due to the decrease of THF, which must be caused by the folate supply from the maternal body to the fetuses. In newborn piglets, levels of “total” plasma folates were much higher than those in adults (nongestating sows), and 5MF was the major folate content. This result may be related to the observation that, after folic acid injection, newborn piglets showed much higher metabolic activity of folic acid to 5MF than adults. Rapid and drastic decrease of plasma folate was observed during nursing in piglets, which is considered to be associated with the decrease of the metabolic activity of folic acid and rapid expansion of body volume together with negative folate intake during the nursing period.
Inhibition of sucrose intake by continuous celiac, superior mesenteric, and intravenous CCK-8 infusions
Authors: Cox J. E. , McCown S. M. , Bridges J. M. , Tyler W. J.
Published: December 2017

Two experiments compared the potency of continuous infusions of cholecystokinin octapeptide (CCK-8) for reducing sucrose intake when administered into abdominal arteries or the jugular vein. Adult, male Sprague-Dawley rats received 22-min infusions of saline or several doses of CCK-8. Sucrose was available for 20 min, beginning 2 min after onset of infusions. In the first experiment, intraceliac CCK-8 in doses of 50, 125, and 312 ng produced significant reductions in intake, but no dose affected intake when administered into the jugular vein. In experiment 2, only the highest dose, 312 ng, suppressed intake when infused into the superior mesenteric artery, and jugular infusions were again ineffective. Behavioral observations indicated that intra-arterial CCK-8 had no affect on feeding within the first several minutes of test meals but accelerated the subsequent decline in incidence of feeding. These results suggest that receptors involved in cholecystokinin satiety are widely distributed within the gastrointestinal tract.
Nitric oxide modulates angiotensin II- and norepinephrine-dependent vasoconstriction in rat kidney
Authors: Parekh N. , Dobrowolski L. , Zou A. P. , Steinhausen M.
Published: December 2017

This study compared the vasoconstrictor action of angiotensin II (ANG II) and norepinephrine (NE) with different levels of nitric oxide (NO) in the kidney of anesthetized rats. In one series of experiments, the drugs were infused intravenously, and systemic NO content was reduced by a NO synthase inhibitor, nitro-L-arginine methyl ester (L-NAME). L-NAME significantly enhanced the renal blood flow (RBF) reduction produced by ANG II from 26 to 49%, but it had no significant effect on the change in RBF induced by NE. Medullary blood flow was not influenced by either ANG II or NE given alone or given after L-NAME. In the second series of experiments, all drugs were infused into the renal artery to avoid their systemic and, hence, extrarenal effects. In these experiments, renal content of NO was increased by the NO donor sodium nitroprusside (SNP), decreased by L-NAME, or restored by replacing endogenous NO by exogenous NO (L-NAME + SNP). Effects of both ANG II and NE on RBF were similarly and significantly attenuated by SNP (60% of control), enhanced by L-NAME (200% of control), and restored by L-NAME + SNP (90% of control, not significant). Our results indicate that NO attenuates the renal vasoconstriction due to ANG II or NE and that the antagonism between vasoconstrictors and NO is not due to a constrictor-induced production of NO because exogenous and endogenous NO were equally effective.
Epidermal growth factor receptor binding and biological activity in the ovary of goldfish, Carassius auratus
Authors: Pati D. , Balshaw K. , Grinwich D. L. , Hollenberg M. D. , Habibi H. R.
Published: December 2017

The receptor binding and biological activity of epidermal growth factor-urogastrone (EGF) was characterized in the follicle-enclosed goldfish oocyte. The binding of 125I-labeled mouse EGF (mEGF) to goldfish ovarian membrane preparation was peptide specific, saturable, reversible, and dependent on time and tissue concentration. Binding data analysis indicated the presence of a single class of high-affinity binding sites with an estimated equilibrium dissociation constant of 4.4 +/- 1.8 x 10(-10) M. The 125I-mEGF binding was displaced by unlabeled mEGF and by human recombinant transforming growth factor-alpha (hTGF-alpha). Both mEGF and hTGF-alpha were found to stimulate reinitiation of oocyte meiosis, as indicated by germinal vesicle breakdown (GVBD). Treatment with mEGF and hTGF-alpha stimulated GVBD from a basal level of 8.5 to approximately 30% with an estimated half-maximal effective dose for EGF of 5.80 +/- 0.82 + 10(-10) and for hTGF-alpha, 1.9 +/- 1.0 x 10(-10) M. Furthermore, treatment with mEGF marginally increased 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (DHP)-induced GVBD without significantly influencing the gonadotropin-induced response. Treatment with either mEGF or hTGF-alpha significantly reduced human chorionic gonadotropin-stimulated testosterone production in a concentration-related manner. These data suggest that members of the EGF family may play a role in the regulation of ovarian function in goldfish.
Effect of naloxone on intake of cornstarch, sucrose, and polycose diets in restricted and nonrestricted rats
Authors: Weldon D. T. , O'Hare E. , Cleary J. , Billington C. J. , Levine A. S.
Published: December 2017

We studied the effect of the opioid receptor antagonist naloxone on intake of three isocaloric diets containing cornstarch, sucrose, or Polycose as the predominant carbohydrate in ad libitum-fed and food-restricted rats. A large body of evidence suggests that opioids affect palatability (reward)-rater than hunger (energy deficit)-driven food intake. We expected food intake to be driven by both energy needs and palatability in ad libitum-fed rats, whereas in food-restricted rats we expected intake to be driven by energy needs with a relatively small palatability component in the preferred sucrose and Polycose diet groups. In the ad libitum-fed rats, naloxone significantly reduced nocturnal intake of all three diets at doses of 0.3, 1.0, and 3.0 mg/kg. In contrast, naloxone failed to alter intake of the cornstarch diet in chronically food-restricted rats. However, naloxone decreased intake of the sucrose diet in food-restricted rats at doses of 0.3, 1.0, and 3.0 mg/kg and decreased intake of the Polycose diet at the 3 mg/kg dose. These data lend further support to the notion that opioids are involved in some other component of feeding than that induced by energy needs.
Comparative bioactivity of atrial, brain, and C-type natriuretic peptides in conscious sheep
Authors: Charles C. J. , Espiner E. A. , Richards A. M. , Nicholls M. G. , Yandle T. G.
Published: December 2017

Although atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) appear to share functional homology, there is doubt concerning a possible endocrine function for C-type natriuretic peptide (CNP) and the relative potency of species-specific forms of these hormones. Accordingly, we have examined the biological effects, interactions, and pharmacokinetics of equimolar doses (0.5 followed by 2.5 pmol.kg-1.min-1, each for 2 h) of species-specific forms of ANP, BNP-26, and CNP-22 in vehicle-controlled studies in normal conscious sheep. Although pharmacokinetics (metabolic clearance rates of 5.7 +/- 1.17, 7.5 +/- 1.36, and 4.7 +/- 0.71 l/min and half-lives of 3.9 +/- 0.42, 2.5 +/- 0.21, and 2.0 +/- 0.18 min for ANP, BNP, and CNP, respectively) are similar, the biological effects and actions on endogenous natriuretic peptide levels differ. Plasma BNP was significantly increased by CNP infusion (P < 0.0001), as was CNP by BNP infusions (P = 0.0009). Compared with ANP and BNP, which were equipotent in stimulating plasma guanosine 3',5'-cyclic monophosphate (cGMP; P < 0.0001 for both) and lowering arterial pressure (P < 0.05 for both) and cardiac output, CNP infusions induced only a small increment in cGMP and had no significant hemodynamic actions. In contrast, all three peptides suppressed plasma aldosterone levels (P < 0.05 for each), yet none induced significant natriuresis. Actions of CNP to increase BNP (and ANP) may account for the observed bioactivity of CNP. The findings show that potentially important interactions occur among all three hormones that need to be considered when interpreting the effects of individual peptides, particularly CNP.
Interaction between norepinephrine and prostaglandin E2 in the preoptic area of guinea pigs
Authors: Sehic E. , Ungar A. L. , Blatteis C. M.
Published: December 2017

The release of norepinephrine (NE) and prostaglandin E2 (PGE2) in the preoptic-anterior hypothalamus (POA) by systemically administered pyrogens suggests that both substances may mediate the febrile response. To investigate their possible interaction, we measured directly the levels of PGE2 in the extracellular fluid of the POA of conscious guinea pigs microdialyzed intrapreoptically with exogenous NE over the entire course of their febrile response to endotoxin. Acidified and buffered NE (NEa, NEb), artificial cerebrospinal fluid (aCSFa, aCSFb), and vehicle (Veha, Vehb) were tested. All but aCSFb depressed the febrile response to endotoxin. The microdialysis of aCSFa, aCSFb, Veha, Vehb, and NEa did not change basal preoptic PGE2 levels. However, NEb, at a dose that by itself did not affect body temperature (Tb), caused a large elevation in preoptic PGE2. The intravenous injection of endotoxin increased the level of PGE2 in the POA. NEb potentiated this increase, whereas NEa, aCSFa, and Vehb reduced it; Veha reduced it for the first 60 min and enhanced it for the last 90 min of the experiment. Thus these data suggest that the low pH of the NE solute and/or its Veh may confound the observed effects of NE on the Tb and preoptic PGE2 induced by endotoxin. We surmise that this is due to a neurotoxic action of the antioxidants and the acidity of the solution on thermosensitive neurons in the POA. Hence, the results of experiments using exogenous, usually acidified, NE preparations that often also contain additives should be interpreted with caution.
CNS actions of serotonin on cardiovascular function: nonadrenergic, noncholinergic mechanisms
Authors: Dedeoglu A. , Fisher L. A.
Published: December 2017

The present studies investigated the mechanisms mediating the cardiovascular changes induced by intracerebroventricular injection of serotonin (5-HT; 100 nmol) in conscious rats. At 5 min after 5-HT injection, arterial pressure and plasma levels of epinephrine were elevated and heart rate was reduced. The pressor response was abolished either by bilateral adrenalectomy or by pretreatment with chlorisondamine plus vasopressin V1 receptor antagonist. The bradycardic response was attenuated by pretreatment with chlorisondamine or a combination of methylatropine, propranolol, and vasopressin V1 receptor antagonist. At 20 min postinjection, arterial pressure and heart rate were both decreased. The reduction of heart rate at this time point was not blocked by the following pretreatments given alone or in combination: methylatropine, propranolol, vasopressin V1 and V2 receptor antagonists, adenosine A1 receptor antagonist, angiotensin-converting enzyme inhibitor, and chlorisondamine. These results suggest that immediately after intracerebroventricular injection of 5-HT, arterial pressure is elevated through the release of epinephrine and vasopressin and that heart rate is reduced via reciprocal changes in cardiac parasympathetic and sympathetic tone. In contrast, adrenergic, cholinergic, vasopressinergic, purinergic, and angiotensinergic mechanisms do not mediate the bradycardia observed at 20 min postinjection.
Plasma ANP levels and protein extravasation during graded expansion with equilibrated whole blood
Authors: Tucker V. L.
Published: December 2017

The relationship between plasma immunoreactive atrial natriuretic peptide (irANP) and radiolabeled albumin clearance (CBSA) in multiple tissues after graded volume stimuli was examined. To obtain a pure volume stimulus, pentobarbital sodium-anesthetized rats (5 or 6 per group) were equilibrated with a reservoir of blood by a femoral arteriovenous shunt, and volume expansion (VE) was produced by adjusting reservoir outflow. Peak increases in central venous pressure (CVP) during VE equal to 2 and 4% of the body weight over 5 min were 3.6 +/- 0.2 and 7.0 +/- 0.3 mmHg, and plasma irANP levels measured at 40 min post-VE were elevated 1.9- and 4.1-fold above baseline, respectively. Graded increases in CBSA measured between 5 and 35 min post-VE occurred in selective tissues, including intestine, visceral fat, lung, and muscle (P < or = 0.05). In separate animals, the level of VE was maintained after 2% VE by slower administration of an additional 2% VE for the remaining 30 min. This resulted in a more sustained CVP elevation and larger increases in irANP levels and CBSA compared with either 2 or 4% VE. Furthermore, equations derived from previous work in this laboratory involving intravenous administration of ANP predicted the magnitude of CBSA elevation during maintained VE. These findings support a role for ANP in regulating transcapillary protein distribution during acute intravascular expansion.
Role of renal nerves in sodium depletion-induced salt appetite
Authors: Thunhorst R. L. , Kirby R. F. , Johnson A. K.
Published: December 2017

The ingestion of water and 0.3 M NaCl solution and the secretion of key hormones were studied in groups of intact and bilaterally renal-denervated rats after extracellular fluid depletion. Hypovolemia with mild hypotension was produced by subcutaneous injections of the diuretic furosemide (10 mg/kg) followed by injections of the angiotensin-converting enzyme inhibitor captopril (5 mg/kg s.c.). Denervated rats drank significantly less of a concentrated saline solution in response to depletion than intact control rats did, but drank similar amounts of water. Denervated rats finished testing in significantly greater negative water and sodium balance compared with controls. Renal denervation did not impair the secretion of renin and aldosterone or the formation of angiotensin I. The diminished sodium intake of denervated rats is not attributable to reduced water and sodium excretion in response to the hypovolemic protocol. These results indicate that the integrity of the renal nerves is important for the normal elaboration of salt appetite in response to hypovolemia/hypotension.
Renal sympathetic nerve activity during cardiac ischemia and reperfusion in rats
Authors: Ustinova E. E. , Schultz H. D.
Published: December 2017

We studied the role played by prostaglandins and oxygen-derived free radicals in mediating reflex changes in renal sympathetic nerve activity (RSNA) during myocardial ischemia and reperfusion. Ligation of the left coronary artery for 20 min and reperfusion for 10 min were performed in anesthetized rats with sinoaortic denervation and with intact cardiac afferent nerves (control, n = 7), with cardiac sympathetic denervation (SD, n = 6), with vagal denervation (VD, n = 7), and with combined SD + VD (n = 6). In control rats, RSNA decreased by 10 +/- 3% from baseline (P < 0.05) during the first minute of ischemia and increased above baseline after 5 min of ischemia, with the maximum increase at the first minute of reperfusion. In rats with SD, RSNA decreased by 19 +/- 4% from baseline (P < 0.05) at the first minute of ischemia and remained depressed during the entire ischemic and reperfusion periods. In rats with VD, RSNA increased by 26 +/- 5% from baseline (P < 0.05) at the first minute of ischemia, and the increase in RSNA at the end of the ischemic period and at reperfusion was greater than in control rats. No changes in RSNA during ischemia and reperfusion were observed with combined SD + VD. Reflex changes in RSNA that occurred at the onset of ischemia in both VD (n = 7) and SD (n = 7) rats were abolished by indomethacin (5 mg/kg i.v., 20 min before ischemia). Reflex changes in RSNA after prolonged ischemia (> 10 min) and during reperfusion in both VD (n = 7) and SD (n = 7) rats were abolished by the antioxidant deferoxamine (20 mg/kg i.v., 20 min before ischemia). Deferoxamine also diminished the increase of RSNA at the onset of ischemia in VD rats. Thus, in rats, the vagal afferent reflex predominates during early ischemia and the sympathetic afferent reflex predominates during prolonged ischemia and reperfusion. Reflex changes in RSNA that occur at the onset of ischemia are mediated by activation of vagal and sympathetic afferent endings by prostaglandins. Reflex changes in RSNA after prolonged ischemia and during reperfusion are mediated by activation of vagal and sympathetic afferent endings by oxygen-derived free radicals.
Relationship between anoxia exposure and antioxidant status in the frog Rana pipiens
Authors: Hermes-Lima M. , Storey K. B.
Published: December 2017

The biochemical adaptations of cellular antioxidant defenses that permit anoxia-tolerant animals to deal effectively with rapid and large changes in oxygen availability, and hence oxidative stress, during transitions from anoxia to normoxia provide insights into the strategies of antioxidant defense that could help to minimize reperfusion injuries to mammalian organs after anoxia/ischemia stress. The present study analyzes the effects of 30 h anoxia exposure followed by reoxygenation on the antioxidant defenses (activities of five enzymes, glutathione status) and lipid peroxidation damage to organs of the leopard frog Rana pipiens (5 degrees C-adapted autumn frogs). Exposure to 30 h anoxia resulted in significant increases in the activities of skeletal muscle and heart catalase (by 53 and 47%), heart and brain glutathione peroxidase (by 75 and 30%), and brain glutathione S-transferase (by 66%). In most cases, enzyme activities had returned to the control values after 40 h aerobic recovery. Activities of superoxide dismutase and glutathione reductase were unaltered in all of the organs, and anoxia/recovery had no effect on any of the enzymes in liver. Glutathione equivalents (GSH-eq) were maintained in four organs during anoxia but decreased by 32% in brain during anoxia. Brain GSH-eq had recovered after 90 min reoxygenation, and, in addition, hepatic GSH-eq rose by 71% after 90 min reoxygenation. The ratio of oxidized glutathione to GSH-eq was also affected by anoxia in an organ-specific way. Lipid peroxidation, assessed as the content of thiobarbituric acid-reactive substances (TBARS), was unaltered in skeletal muscle and liver after 30 h anoxia exposure or short (25 and 90 min)- or long-term (40 h) periods of reoxygenation, indicating that cycles of natural and survivable anoxia/reoxygenation occur without significant increase in TBARS in selected organs. Overall, the data demonstrate that elements of the antioxidant system of R. pipiens are induced during anoxia exposures as a possible preparation for dealing with potentially harmful oxygen reperfusion stress.
Renin secretion in conscious Lyon hypertensive rats
Authors: Bertolino S. , Julien C. , Medeiros I. A. , Cuisinaud G. , Vincent M. , Barres C.
Published: December 2017

To characterize the renin secretory profile in Lyon hypertensive (LH) rats, renin responses to reductions of arterial pressure and beta-adrenoceptor stimulation were assessed in conscious unrestrained LH (n = 13) and Lyon normotensive (LN, n = 14) rats under normal-salt diet. Mean arterial pressure (MAP) in the infrarenal aorta was recorded beat to beat for 3 h. Then, plasma renin concentration (PRC) was measured 1) in basal conditions, 2) during 10-mmHg stepwise reductions of MAP down to 60 mmHg using a chronically implanted aortic inflatable cuff, and 3) during isoprenaline infusion (62.5, 125, and 250 ng.kg-1.min-1 iv). Compared with LN, LH rats had an elevated MAP (146 +/- 3 vs. 111 +/- 1 mmHg, P < 0.001) and decreased PRC [4.2 +/- 0.6 vs. 8.2 +/- 0.8 ng angiotensin (ANG) I.ml-1.h-1, P < 0.001] and kidney renin content (216 +/- 14 vs. 1,149 +/- 103 micrograms ANG I.h-1.g-1, P < 0.001). Pressure-dependent renin release occurred below 90 mmHg in LN rats and below 80 mmHg in LH rats, and its sensitivity in the low-pressure range did not differ between strains. Isoprenaline-induced increases in PRC were weaker (P < 0.01) in LH than in LN rats. In additional LH and LN rats (n = 6-8), acute ANG II AT1-receptor blockade with losartan (20 mg/kg, followed by 10 mg.kg-1.h-1 iv for 2 h) induced lesser (P < 0.001) PRC increases in LH than in LN rats. Renin responses to isoprenaline remained blunted (P < 0.01) during losartan infusion in LH rats. We conclude that, in LH rats, renin secretion is independent of MAP in the range of its spontaneous variations and is poorly responsive to beta-adrenoceptor stimulation, the alteration of which cannot be explained by an enhanced feedback inhibition by ANG II.
Nonuniform sympathetic nerve responses after sustained elevation in arterial pressure
Authors: Claassen D. E. , Morgan D. A. , Hirai T. , Kenney M. J.
Published: December 2017

We tested the hypothesis that sustained increases in mean arterial pressure (MAP) produce nonuniform changes in regional sympathetic nerve discharges (SND) after the return of MAP to control levels. Renal, adrenal, splanchnic, and lumbar SND were recorded before, during, and after a 30-min elevation in MAP produced by phenylephrine (PE) infusion in alpha-chloralose-anesthetized spontaneously hypertensive (SH) rats. SND remained reduced from control values after PE infusion, despite the return of MAP to control levels. Importantly, the duration of poststimulus sympathoinhibition was significantly less in adrenal and splanchnic SND compared with renal and lumbar SND. In sinoaortic-denervated SH rats, SND remained at control levels during and after PE infusion. Simultaneous recordings of aortic depressor nerve (ADN) activity and SND demonstrated that prolonged renal and lumbar sympathoinhibition occurred even when ADN activity fell below control levels after PE infusion. We conclude that poststimulus responses of efferent SND in SH rats are regionally nonuniform and that renal and lumbar sympathoinhibitory responses are not mediated solely by prolonged increases in afferent baroreceptor nerve activity.
RU-486 blocks differentially suppressive effect of stress on in vivo anti-KLH immunoglobulin response
Authors: Fleshner M. , Brennan F. X. , Nguyen K. , Watkins L. R. , Maier S. F.
Published: December 2017

Exposure to stressors can affect various aspects of immune function, including the antibody response. We have previously reported that rats exposed to an acute session of inescapable tail shock (IS) show long-term reductions in anti-keyhole limpet hemocyanin (KLH) immunoglobulin (Ig) M and IgG and a failure to expand Th1-like cells in response to KLH. To further investigate the potential role of decreased Th1-like cells in the IS-induced reduction of anti-KLH Ig, we examined two isotypes of IgG, IgG1 and IgG2a. Isotype switching is under cytokine control. Interleukin-4 helps B cells switch from making IgM to making IgG1, whereas interferon (IFN)-gamma helps B cells switch from making IgM to making IgG2a. In this paper we report that IS exposure reduces IFN-gamma levels 4 days after exposure to IS+KLH compared with immunized home cage controls. In addition, IS exposure reduced the Th1 cytokine-sensitive anti-KLH IgG2a but not Th2 cytokine-sensitive anti-KLH IgG1. This pattern of isotype reduction suggests that a failure to expand the Th1 cell, which results in less IFN-gamma, may contribute to the the IS-induced reduction in anti-KLH Ig. Glucocorticoids (GCs) differentially regulate Th1 and Th2 cells. Administration of the type II GC receptor antagonist RU-486 before IS blocked the IS-induced suppression in anti-KLH IgM, IgG, and IgG2a. Corticosterone (2.5 mg/kg), however, did not produce the suppression in anti-KLH Ig. These results support a role of corticosterone in mediating IS-induced reductions in in vivo antibody.
Renal organic anion secretion: evidence for dopaminergic and adrenergic regulation
Authors: Halpin P. A. , Renfro J. L.
Published: December 2017

To examine possible regulatory control of renal proximal tubule organic anion secretion, winter flounder (Pleuronectes americanus) proximal tubule primary cultures were mounted in Ussing chambers. Unidirectional fluxes of [2,4-(14)C]dichlorophenoxyacetic acid were determined under short-circuited conditions. Phorbol 12-myristate 13-acetate (1 microM) caused a significant (P < 0.01) inhibition of net 2,4-dichlorophenoxyacetic acid secretion. Preincubation with staurosporine (1 microM) blocked the phorbol 12-myristate 13-acetate-induced decrease in secretion. Neither forskolin (10 microM) nor W-7 (20 microM) had any effect on net transport. Elevation of intracellular calcium activity with either A-23187 or thapsigargin produced a slight, transient decrease in transport. Addition of dopamine (1 microM) to the peritubular side, but not the luminal side, caused a significant (P < 0.01) decrease in net secretion. Both the alpha-adrenergic agonist oxymetazoline (10 microM) and depletion of intracellular Na+ transiently, but significantly (P < 0.05), increased net transport. The data indicate that renal organic anion excretion may be regulated through dopaminergic inhibition and alpha-adrenergic stimulation of net transepithelial secretion.