bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclic nucleotide responses in control and cystic fibrosis labial glands
Authors: Allan B. J. , Izutsu K. T. , Ramsey B. W. , Schubert M. M. , Ensign W. Y. , Truelove E. L.
Published: December 2017

Adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) levels were measured in labial gland slices from controls and patients with cystic fibrosis (CF). Incubation in vitro with 10 microM epinephrine, 50 microM isoproterenol, or 10 microM carbachol increased cAMP levels by 2.3-fold, 3.1-fold, and 1.8-fold, respectively, in control glands and by similar amounts in CF glands. The only statistically significant CF-related difference was a decreased response to isoproterenol. Addition of MIX (3-isobutyl-1-methylxanthine) increased cAMP levels in control and CF glands by an order of magnitude under all conditions but did not eliminate the CF-related decrease in cAMP level obtained with isoproterenol. cGMP levels were measured only in the presence of MIX. Incubation with carbachol nearly doubled cGMP levels in control and CF glands but only the control gland response approached statistical significance (P = 0.06). cGMP levels in CF glands were nearly threefold greater than those in control glands, and disease-related differences obtained in the presence of carbachol and isoproterenol were statistically significant.
Fetal swallowing: correlation of electromyography and esophageal fluid flow
Authors: Sherman D. J. , Ross M. G. , Day L. , Ervin M. G.
Published: December 2017

Patterns of fetal drinking behavior were quantified in five singleton fetuses (128 +/- 1 days gestation) by computer analysis of laryngeal-esophageal electromyography (EMG) and thoracic esophageal fluid flow. Esophageal flow was noted to be bidirectional with an average antegrade flow-to-retrograde flow ratio of 4.4 +/- 1.5. Retrograde esophageal flow coincided with diaphragmatic contractions, suggesting that inspiratory gastroesophageal pressure gradients may be operative. The regurgitated fluid was returned to the fetal rumen by thoracic esophageal contractions. Significant net fluid intake was noted during periods of primarily unidirectional antegrade esophageal flow. Fetuses swallowed an average of 35 +/- 9 ml/h during the 12-h study, extrapolating to an average daily volume of 840 +/- 224 ml. An EMG “propagated swallow” representing coordinated contractions of the thyrohyoid, nuchal esophagus, and thoracic esophagus averaged 43 +/- 3 swallows/h and was highly correlated with net esophageal flow. Nearly 60% of the total fluid intake occurred during “bouts” of propagated swallows, which represented only 8% of the study period. Bouts averaged 11.7 +/- 0.4 propagated swallows, lasted 2.1 +/- 0.2 min, and occurred every 27.6 +/- 1.7 min. Although EMG swallowing activity was similar, there were significant differences among fetuses in net esophageal fluid flow and volume per propagated swallow. We speculate that fetal fluid intake is dependent on the availability and physical properties of the swallowed fluid, whereas swallowing activity is primarily related to cortical maturation and thirst stimulation.
Vascular reactivity of the coronary artery in rainbow trout (Oncorhynchus mykiss)
Authors: Small S. A. , MacDonald C. , Farrell A. P.
Published: December 2017

Vascular reactivity of the large coronary artery of a lower vertebrate was investigated for the first time in this study. The responses of vascular rings to various pharmacological agents were measured using isometric force transducers. Coronary arteries from rainbow trout, Oncorhynchus mykiss, contracted with acetylcholine and predominantly relaxed with isoproterenol, epinephrine, norepinephrine, and serotonin. Atenolol blocked the adrenergic relaxation, suggesting a predominance of beta 1-adrenoceptors. Nitroglycerin and sodium nitroprusside relaxed vascular rings. Responses to histamine and bradykinin were absent in this tissue. Adenosine, ADP, and ATP caused contractions that could be blocked by theophylline. The difference in vascular reactivity between that typically found in mammalian coronary arteries and that reported here for rainbow trout are discussed.
Relationships between breathing activity and heart rate in fetal baboons
Authors: Myers M. M. , Fifer W. , Haiken J. , Stark R. I.
Published: December 2017

Coordination between breathing and heart rate (HR) is known to occur in many species and is commonly called respiratory sinus arrhythmia (RSA). In this report, we provide evidence that a homologous phenomenon can be demonstrated in the fetuses of nonhuman primates. In chronically instrumented fetal baboons we found cyclical variations in HR that were coincident with fetal breathing movements. We found clear instances of fetal RSA in each of three baboon fetuses. The average change in HR with each fetal breath was approximately 2 beats/min. Fetal breaths were associated with an acceleration/deceleration cycle in HR, and the onset of accelerations was coincident with the onset of inspiratory activity. These studies indicate that in baboons integration of respiratory and cardiovascular control mechanisms develop in utero.
Role of nonworking muscle on blood metabolites and ions with intense intermittent exercise
Authors: Lindinger M. I. , Heigenhauser G. J. , McKelvie R. S. , Jones N. L.
Published: December 2017

The exchange of ions between blood and inactive muscle was studied in healthy males (n = 11) who performed four 30-s bouts of maximum isokinetic leg exercise, with 4 min of rest between bouts; recovery was followed for 90 min. Blood was sampled from the brachial artery and antecubital vein from inactive arm, and biopsies were taken from the nonworking deltoid muscles. During exercise, whole blood and plasma arteriovenous (a-v) differences across the arm showed increased net uptake of lactate (Lac-), K+, Na+, Cl-, glycerol, and O2. Arm glucose uptake also increased during exercise and the last 30 min of recovery, but there was no change in muscle glycogen content. Deltoid intracellular Lac- concentration [( Lac-]) increased 2.5-fold to 8.2 +/- 1.4 meq/l during exercise and 25 min of recovery. Despite evidence of uptake from blood and plasma a-v differences, deltoid intracellular K+, Na+, and Cl- concentrations did not change. During recovery, arm a-v differences showed no Lac- release, but Cl- and Na+ were released to venous blood for at least 90 min of recovery. During repeated exercise, the elevated Lac- uptake (a-v [Lac-] is 5-8 meq/l) and a HCO3- release (a-v HCO3- concentration is -8-11 meq/l) by the arm was suggestive of a possible anion exchange (Lac-/HCO3-). It is concluded that during heavy exercise non-working muscles take up and oxidize significant amounts of Lac-. Other inactive tissues also play a role in the regulation of ion and metabolite concentrations of blood.
Influence of increased metabolic rate on [13C]bicarbonate washout kinetics
Authors: Barstow T. J. , Cooper D. M. , Sobel E. M. , Landaw E. M. , Epstein S.
Published: December 2017

The effect of changes in metabolic rate on the dynamics of CO2 exchange among its various compartments in the human body is not well understood. We examined CO2 dynamics in six healthy male subjects using an intravenous bolus of [13C]bicarbonate. Subjects were studied while resting, during light exercise [50% of the lactate threshold (LT), 3-4 times resting O2 uptake (VO2)], and during moderate exercise (95% of the LT, 6 times resting VO2). The sum of three exponential terms well described the washout of 13CO2 in exhaled breath both at rest and during each exercise level despite substantial increases in metabolic rate accompanying the exercise studies. Average recovery of 13C label rose from 67% during rest to 80% during light and moderate exercise (P less than 0.01). The estimate of CO2 elimination (VCO2) calculated from the washout parameters and corrected for recovery was in very good agreement with the VCO2 directly measured simultaneously breath by breath (r = 0.993, SE for VCO2 = 0.079 l/min). By use of a three-compartment mammillary model, the quantity of CO2 in the central pool (Q1) doubled from rest to light exercise (233 +/- 60 to 479 +/- 76 mmol, P less than 0.01) but did not change further with moderate exercise (458 +/- 74 mmol). Rate constants for exchange between pools and for irreversible loss from the system tended to increase with metabolic rate, but there was large variation in the responses. We conclude that the compartmental dynamics of CO2 transport and storage are very sensitive to changes in metabolic rate induced by exercise.
Improved method for estimating Ca uptake in vascular smooth muscle using compartmental analysis
Authors: Massaldi H. A. , Copello J. , Muller A. , Villamil M. F.
Published: December 2017

A comparative study on the modeling aspects of Ca uptake in vascular smooth muscle is presented with particular emphasis on determination of the influx rate and its standard error for one- and two-compartment models. Experimental data from our laboratory of 45Ca uptake by dog carotid arteries were optimally fitted to a one-compartment model and were used to compare different estimation methods and experiment designs. Reparameterization of the model equation yielded an expression that allows direct estimation of the influx rate and its standard error. Experiment design with replicated sampling at three to four times were found to provide the highest estimation precision and successful comparisons of influx rates under treatment and control conditions. Two-compartment model data reported in the literature for Ca uptake by cells were reprocessed, yielding standard errors for the rate constant of the fast component an order of magnitude larger than the mean estimate. For this case, a three-parameter variant of the one-compartment model was developed that described the data with acceptable standard errors. Overall we found that the choice of the model that fitted Ca uptake data best required consideration of parameter estimate precision comparisons in addition to F tests of significance between alternate models.
Reduced adipsin mRNA and circulating adipsin protein are modulated by adrenal steroids in obese Zucker rats
Authors: Johnson P. R. , Spiegelman B. , Rosen B. , Turkenkopf I. , Ree H. , Greenwood M. R.
Published: December 2017

We investigated expression of the adipose-specific serine protease adipsin in genetically obese Zucker rats and whether adrenalectomy modifies expression. Adipsin mRNA levels were determined by slot blot and Northern blot analysis of total RNA samples extracted from epididymal adipose tissue and isolated retroperitoneal adipocytes of obese (fa/fa) and homozygous lean (Fa/Fa) Zucker rats. Both 30-day-old and 4-mo-old animals were analyzed in experiment 1. In experiment 2, 10-wk-old obese and lean rats were either bilaterally adrenalectomized or sham operated, and adipsin mRNA levels were determined on tissue and cell samples 2 wk postsurgery. In both experiments, serum adipsin protein was determined by Western blot analysis and plasma insulin by radioimmunoassay. The data show that both adipsin mRNA and adipsin protein are reduced in obese compared with lean rats and that adrenalectomy restores these values toward normal in obese rats. The data thus suggest that adrenal steroids are involved in modulating adipsin expression in obese Zucker rats and that insulin may be an intermediary factor in such modulation.
Cardiovascular effects of microinjection of ANF and brain natriuretic peptide into ventrolateral medulla
Authors: Ermirio R. , Avanzino G. L. , Ruggeri P. , Bergaglio M. , Calaresu F. R.
Published: December 2017

Cardiovascular effects of microinjection of atrial natriuretic factor (ANF) into 77 sites of the ventrolateral medulla (VLM) were investigated in urethan-anesthetized rats. Changes in mean arterial pressure (MAP) and heart rate (HR) in response to injections of glutamate into these sites were used to determine that they contained cardiovascular neurons. ANF (20 nl of 10(-7) M) decreased MAP [-8.9 +/- 1.5 (SE) mmHg] and HR [-9.0 +/- 2.8 (SE) beats/min] in 5 of 36 vasopressor sites identified by glutamate located in the more rostral and lateral aspect of the rostral VLM (RVLM); no effect was elicited in the other 31 RVLM sites. ANF decreased MAP (-10.4 +/- 2.4 mmHg) and HR (-9.8 +/- 3.0 beats/min) in 25 of 41 depressor sites distributed throughout the caudal VLM (CVLM); no response was observed in the other 16 CVLM sites. Brain natriuretic peptide (BNP) was microinjected (20 nl of 10(-7) M) in 21 VLM sites, before or after microinjection of ANF. BNP and ANF elicited similar results in 17 sites, a decline in MAP and HR in 10 sites, and no effect in 7 sites. In the remaining four cases ANF caused a decline in MAP and in HR, whereas BNP had minimal or no effect. Cardiovascular responses to ANF microinjection into the RVLM and CVLM support the hypothesis that ANF is involved in the transmission of baroreceptor information from the nucleus tractus solitarii to these medullary regions. The similarity of the results obtained with BNP and ANF suggests that these peptides may serve similar roles in medullary pathways involved in the control of the cardiovascular system.
Calcium deprivation increases salt intake
Authors: Tordoff M. G. , Ulrich P. M. , Schulkin J.
Published: December 2017

Relative to rats fed chow or semisynthetic control diet, rats fed Ca2(+)-deficient diet increased daily "spontaneous" intake of 0.3 M NaCl solution by as much as eightfold. Intake of 0.3 M NaCl increased in monotonic relationship to the severity of Ca2+ deficiency, which was manipulated by both duration of depletion (0-32 days) and dietary Ca2+ content (0-50 mmol/kg Ca2+). The increased intake was specific to either Na+ or saltiness; relative to controls, Ca2(+)-deprived rats drank more of a wide range of NaCl solutions (0.05-0.50 M) but the same volume of 0.37 mM sucrose octaacetate (bitter), slightly more 2.5 mM citrate (sour), and significantly less 2.5 mM saccharin (sweet). Although urine volume of Ca2(+)-deprived rats was increased, total Na+ excretion was slightly decreased. Adrenal weights, hematocrit, and plasma concentrations of Na+, aldosterone, and angiotensin I were all normal. These results reveal that Ca2+ deficiency increases NaCl intake and thus challenge the notion that salt appetite is a specific response to perturbed Na+ homeostasis.
Body temperature effects on hypoxic and hypercapnic responses in awake rats
Authors: Maskrey M.
Published: December 2017

During surgery under pentobarbital sodium anesthesia, 20 rats had heat exchange devices implanted into their abdominal cavity. After recovery, 14 rats underwent two sets of trials, one in which body core temperature (Tbc) was lowered to 34.5-35.5 degrees C and another in which Tbc was raised to 40.5-41.5 degrees C. Rats breathed air and hypoxic (15, 11, and 7% O2 in N2) and hypercapnic (2, 4, and 6% CO2 in air) gas mixtures. Respiratory responses were measured using a barometric method and compared with data from the same rats breathing the gas mixtures at normal Tbc (37.5-38.5 degrees C) before surgery. The six remaining rats served as controls (Tbc unchanged). Lowering Tbc increased respiration in air, whereas heating had no effect. Hypothermia and severe hypoxia combined to inhibit respiration when compared with breathing air at lowered Tbc or low O2 at normal Tbc. The CO2 response slope became steeper when Tbc was raised, suggesting an increased CO2 sensitivity. Possible sites for the hypothermia-hypoxia interaction and the hyperthermia-hypercapnia interaction are discussed.
Brain histamine regulates pressor responses to peripheral hyperosmolality
Authors: Akins V. F. , Bealer S. L.
Published: December 2017

The role of brain histamine (HA) in the pressor response to peripheral hyperosmolality was investigated in the conscious Sprague-Dawley rat. Increased mean arterial pressure was observed during a 30-min intravenous infusion of hypertonic saline (HTS; 10 microliters.100 g body wt-1 x min-1) in vehicle-treated controls (20.1 +/- 3.8 mmHg) and in animals centrally pretreated with the specific H2-antagonist, cimetidine (15.0 +/- 3.7 mmHg). However, this pressor response was abolished in a dose-dependent manner after intracerebroventricular injection of the H1 antagonist promethazine. In other experiments, brain tissue microdissected from the supraoptic nucleus (SON), paraventricular nucleus (PVN), and posterior hypothalamic region showed significantly lower levels of total tissue HA after 60 min of intravenous HTS infusion compared with tissue taken from control animals receiving an isotonic infusion. Microdialysis in the region of the PVN or SON before and during HTS infusion showed increased extracellular concentrations of HA in the SON (24.4 +/- 10.9%) during infusion. No change in extracellular HA concentration was seen in the PVN during HTS infusion. These results support the conclusion that endogenous brain HA is involved in the pressor response to peripheral hyperosmolality.
Circulating angiotensin II and drinking behavior in rats
Authors: Pawloski C. M. , Fink G. D.
Published: December 2017

This study was designed to investigate the effects on water drinking of acute and chronic increases in circulating angiotensin II (ANG II) concentrations in rats. Experiments were conducted in male Sprague-Dawley rats chronically instrumented with femoral arterial and venous catheters and permanently housed in metal metabolism cages. ANG II was infused intravenously either acutely (30 min-2 h) or chronically (3 days) in a dose range of 10-60 ng/min. In no instance did such infusions cause a statistically significant increase in water intake. Other experiments examined the influence of ANG II (10 ng/min iv) on drinking elicited by infusion of hypertonic sodium chloride (1.5 M at 3.5 microliters/min). ANG II administration did not increase drinking to a hypertonic saline stimulus or lower the osmotic threshold for drinking. Nitroprusside (12 micrograms/min) was infused for 30 min to produce hypotension and drinking. Water intake associated with this stimulus was not changed by blocking ANG II formation with enalapril (2 mg/kg iv) or by concomitant infusion of ANG II (10 ng/min iv). Finally, plasma ANG II concentrations were measured before and after 1-h intravenous infusion of saline or ANG II to determine the levels of circulating ANG II produced by the infusion rates used here. It is concluded that the range of circulating ANG II concentrations found under most physiological conditions in rats does not directly stimulate drinking or participate importantly in osmotic or hypotension-induced drinking.
Forebrain rhythm generators influence sympathetic activity in anesthetized cats
Authors: Kenney M. J. , Gebber G. L. , Barman S. M. , Kocsis B.
Published: December 2017

Autospectral and coherence analyses were used to study the frequency-domain relationships between frontal-parietal cortical activity [electroencephalogram (EEG)] and the discharges of the interior cardiac and renal sympathetic nerves of baroreceptor-denervated and vagotomized cats anesthetized with either alpha-chloralose or pentobarbital sodium. Delta slow-wave activity in the EEG was correlated to sympathetic nerve discharge (SND) as shown by sharp peaks between 0.5 and 4 Hz in the coherence function. The relationship was stronger in chloralose- than in pentobarbital-anesthetized cats. Coherence of the two signals could be attributed to descending influences of forebrain delta slow-wave generators on sympathetic circuits, since midbrain transection preferentially reduced the power in SND at frequencies that cohered to the EEG before transection. In contrast, the power in the EEG was not reduced by midbrain transection. The relationship between cortical delta slow-wave activity and SND was stronger during than between cortical spindlelike events that lasted 1-3 s and recurred once every 5-10 s. These events were similar to cortical spindles observed during the early stages of sleep and under light barbiturate anesthesia. These observations raise the possibility that the influences of forebrain delta slow-wave generators on SND are gated by thalamic mechanisms normally involved in the sleep-wake cycle.
Preheparinization improves organ function after hemorrhage and resuscitation
Authors: Wang P. , Singh G. , Rana M. W. , Ba Z. F. , Chaudry I. H.
Published: December 2017

Recent studies indicate that heparinization before hemorrhage maintains microvascular patency in the liver and kidney during and after severe hemorrhagic shock. However, it is not known whether preheparinization has any protective effects on organ function after hemorrhage and resuscitation. To study this, unanesthetized rats (with or without preheparinization) were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the maximum shed blood volume was returned in the form of Ringer lactate (RL). They were then resuscitated with four times the volume of the shed blood with RL. Cardiac output (CO), [3H]inulin clearance (CIn; renal function), hepatic microvascular blood flow (HMBF), and hepatocellular function (HF), i.e., maximal velocity of indocyanine green clearance (Vmax), were determined 1.5 h after resuscitation. Although CO decreased in both groups, the values in preheparinized rats were significantly higher than in the nonheparinized rats. The improvement in CIn as well as HMBF followed the same trends. HF (Vmax) was significantly depressed in the nonheparinized rats but was maintained in preheparinized rats. Thus administration of heparin before the onset of hemorrhage improves CO and renal function and restores HF to control after hemorrhage and resuscitation. These protective effects of preheparinization could be due to the maintenance of microvascular patency and prevention of blood sludging during and after hemorrhage.
A method for continual monitoring of bone resorption in rats: evidence for a diurnal rhythm
Authors: Muhlbauer R. C. , Fleisch H.
Published: December 2017

A method has been developed to monitor bone resorption (BR) based on the urinary excretion of [3H]tetracycline ([3H]TC) from chronically prelabeled rats. This is possible because the [3H]TC released from bone has been found to be in a form that is not or only poorly bound to apatite and thus not reincorporated into newly formed bone. When BR was increased by means of dietary calcium restriction, parathyroid hormone (PTH) infusion, or retinoid injections, urinary [3H]TC doubled. When BR was inhibited by feeding calcium supplements or administration of dichloromethylenebisphosphonate, [3H]TC excretion dropped by two-thirds. Thyroparathyroidectomy inhibited [3H]TC excretion by one-third. The results obtained with this technique are therefore similar to those obtained with other methods such as 45Ca kinetics. The effect of dietary manipulations on BR was detected within 6 h of changing diet. Furthermore, a strong diet-dependent but PTH- and calcitonin-independent diurnal rhythm in BR was found. By use of this technique, bone resorption can be assessed continuously over long periods, and the acute regulation of bone resorption can be studied for the first time.
Effect of angiotensin-converting enzyme inhibitor on salt appetite and thirst of BALB/c mice
Authors: Weisinger R. S. , Blair-West J. R. , Denton D. A. , McBurnie M. , Ong F. , Tarjan E. , Williams R. M.
Published: December 2017

The role of angiotensin II (ANG II) in Na-depletion-induced Na appetite of mice was investigated. Intraperitoneal injection of the angiotensin-converting enzyme inhibitor captopril at 1.7 mg/mouse (high dose) decreased the Na intake of the Na-depleted (furosemide-treated) mice by 80-85%. The decrease in Na intake was restored to the initial level by concurrent subcutaneous infusion of ANG II. High dose of captopril also decreased the Na intake of fluid-deprived, Na-depleted mice. High dose of captopril did not alter water intake in any of the four conditions examined, i.e., in fluid-replete, Na-depleted, water-deprived, or fluid-deprived, Na-depleted mice. Low dose of captopril (1.7 microgram/mouse) tended to or significantly enhanced Na intake of Na-depleted mice. Low dose of captopril, however, did not enhance water intake in any of the conditions examined. Both high- and low-dose captopril treatment decreased food intake in water-deprived mice, whether or not the mice were Na depleted as well. The addition of captopril (0.1 or 1.0 mg/ml) to the drinking water did not influence Na or food intake. Water intake was enhanced during treatment with the low but not with the high dose of captopril. The results are consistent with the proposition that ANG II is involved in the Na appetite of Na-depleted mice. ANG II does not appear to have a role in water intake of Na-depleted or water-deprived mice, but neural mechanisms in which angiotensin has a role may influence food intake of water-deprived mice.
Insulin modifies flavor aversions and preferences in real- and sham-feeding rats
Authors: Vanderweele D. A. , Deems R. O. , Kanarek R. B.
Published: December 2017

In separate, parallel experiments, rats were allowed to sham or real feed a flavored sweetened condensed-milk solution after a 17.5-h fast. Coinciding with administration of the milk were injections of insulin or vehicle (saline). Insulin had no effect on intake in the real feeding situation, and flavors paired with insulin (0.8, 2.5, or 5.0 U/rat) were avoided, relative to saline-paired flavors. In sham-feeding rats, insulin (0.8 U/rat) significantly reduced the amount of milk consumed, and flavors paired with insulin injection were preferred, relative to saline-paired ones. Insulin produced a relatively larger hypoglycemia during sham feeding than during real feeding. Thus it appears that insulin-paired flavors of milk may be preferred by animals when they are ingested in sham feeding but not in animals real feeding. Perhaps rapid gastric emptying, as would occur with a liquid diet, accompanied by increased insulin levels, leads to malaise and flavor aversion.
Cortisol directly stimulates differentiation of chloride cells in tilapia opercular membrane
Authors: McCormick S. D.
Published: December 2017

Opercular membranes from freshwater tilapia (Oreochromis mossambicus) were maintained in vitro for 4 days and exposed to several concentrations of cortisol (0, 0.01, 0.1, 1, and 10 micrograms/ml). Chloride cell size, number, and Na(+)-K(+)-ATPase content were examined using a fluorescent mitochondrial dye (dimethylaminostyrylethylpyridiniumiodine), a fluorescent analogue of ouabain (anthroylouabain) that binds specifically to Na(+)-K(+)-ATPase, and a cytological stain specific for plasma and tubular membranes. In the absence of cortisol, chloride cell density of the freshwater tilapia opercular membrane decreased (from initial levels of 6,114 +/- 451 to 18 +/- 9 cells/cm2) and was restored by cortisol in a dose-dependent manner. Chloride cell height (5.5 +/- 0.3 microns initially and 7.8 +/- 0.5 microns after 4 days in vitro) increased twofold (13.1 +/- 0.7 microns) after exposure to 1 microgram/ml cortisol. Initially and after 4 days in control medium, there was no detectable staining with anthroylouabain; exposure to 1 microgram/ml cortisol resulted in the appearance of numerous anthroylouabain-positive chloride cells. Without cortisol, Na(+)-K(+)-ATPase activity of the opercular membrane remained constant through 4 days of culture (0.4-0.6 mumol ADP.mg protein-1.h-1); addition of cortisol caused a dose-dependent increase to a maximum of 1.2 +/- 0.1 mumol Pi.mg protein-1.h-1. In vitro cortisol also maintained the size, density, and appearance of chloride cells from opercular membrane of seawater-adapted tilapia. The results indicate that in vitro cortisol exposure causes morphological and biochemical differentiation of the seawater form of the chloride cell.
Role of atrial appendages in modulating stimulated plasma atrial natriuretic peptide levels in conscious rats
Authors: Hoffman A. , Grossman E. , Keiser H. R.
Published: December 2017

To evaluate the role of the atrial appendages in modulating plasma levels of atrial natriuretic peptide (ANP), we applied a series of both acute and chronic stimuli in conscious, chronic, bilaterally atrial-appendectomized (APP) and sham-operated control rats. Basal plasma ANP levels and urinary sodium excretion were normal in all rats after APP. The release of ANP was markedly blunted to acute volume expansion (+67% vs. +357% in controls, P less than 0.01) but was only moderately reduced after norepinephrine infusion (+106% vs. +212%, P less than 0.05) and was normal after acute salt load [+148% vs. +180% in controls, not significant (NS)]. Furthermore, plasma levels of ANP were increased normally in APP rats treated with deoxycorticosterone acetate (270 + 18 vs. 296 + 14 pg/ml in controls, NS) and in APP rats with congestive heart failure induced by a large arteriovenous (a-v) fistula between the aorta and the vena cava (306 +/- 18 vs. 302 +/- 12 pg/ml, NS). Sodium excretion patterns were similar in chronically stimulated APP and control rats. The results demonstrate that, although APP reduces the response of ANP release to acute volume expansion, it does not do so to other stimuli of either acute or chronic nature, suggesting that there is no permanent defect in the ability of APP rats to secrete ANP. These studies confirm that the atria are the major source for ANP release into the circulation after acute intravascular volume expansion. However, other tissue sources may contribute significantly to the levels of circulating ANP in response to this and other acute and chronic stimuli.
Alteration of baroreflex control of forearm vascular resistance by dietary fatty acids
Authors: Mills D. E. , Mah M. , Ward R. P. , Morris B. L. , Floras J. S.
Published: December 2017

The effects of dietary safflower (control, n = 10), borage (n = 9), and fish oil (n = 10), as sources of linoleic, gamma-linolenic, and eicosapentaenoic acid, respectively, at a dose of 4.5 ml/day for 4 wk, on cardiovascular responses to lower body negative pressure (LBNP) were studied in normotensive humans in a randomized, double-blind design. Pre- and postsupplementation, subjects were exposed to 5 min of -10 and -40 mmHg LBNP. Blood pressure (BP), heart rate (HR), forearm blood flow (FBF), forearm vascular resistance (FVR), and plasma norepinephrine (PNE) were measured at each level. Subjects were then exposed to a cold-pressor test, isometric handgrip, and forearm ischemia. At pretest, LBNP reduced BP and FBF and increased HR and FVR in all groups. After diets, the PNE and vasoconstrictor responses to -40 mmHg LBNP, as well as the reflex vasodilation on its cessation, were significantly augmented by borage oil. No diet differences were observed in the HR responses to LBNP or in the responses to the other tasks, with the exception that fish oil increased FBF after forearm ischemia. These data indicate that borage oil augments the arterial baroreflex control of vascular resistance. The vasodilatory effects of fish oil may be mediated via local mechanisms.
Entrainment of circadian rhythms with 26-h bright light and sleep-wake schedules
Authors: Eastman C. I. , Miescke K. J.
Published: December 2017

Subjects followed a 26-h sleep-wake schedule and were exposed to various light patterns while living at home exposed to the conflicting 24-h zeitgebers. In one protocol, a 26-h light pattern containing evening bright light was compared with a natural-light-only pattern. In another protocol, the evening-light pattern was compared with a morning-light pattern. Rectal temperature was continuously measured. Sleep times were estimated from daily sleep logs. The sleep times of most subjects conformed fairly well to the 26-h sleep-wake schedule, although the evening-light condition produced slightly better results. A larger proportion of subjects had their temperature rhythm entrained to the 26-h schedule during the evening-light condition than during the morning-light or natural-light conditions. Entrainment to the 26-h schedule was achieved in 74% (14/19) of the subjects tested in the evening-light condition. This study shows that non-24-h bright light and sleep-wake schedules can be used to phase shift and entrain human circadian rhythms, despite the presence of the conflicting 24-h zeitgebers.
SCN lesions block responses to systemic melatonin infusions in Siberian hamsters
Authors: Bartness T. J. , Goldman B. D. , Bittman E. L.
Published: December 2017

The role of the suprachiasmatic nuclei (SCN) in the response to short-day melatonin (MEL) signals was examined in long-day-housed pinealectomized (PINX) Siberian hamsters. Five- or ten-hour MEL infusions that mimicked the peak nocturnal durations of serum MEL levels in long or short days, respectively, or control saline infusions were given for 5 wk. Half the hamsters in each infusion group also received bilateral electrolytic SCN lesions. The 10-h MEL infusions reduced testes weight, body and fat pad weights, and serum prolactin (PRL) and follicle-stimulating hormone (FSH) concentrations in unoperated controls. These short-day-type effects were blocked by SCN lesions, which often produced hyperprolactinemia. Circadian rhythms of locomotor activity were disrupted or sparse in hamsters with lesions in or near the SCN. In a second experiment, 5 wk of long-day-like, short-duration (5-h) MEL infusions were administered to hamsters that had been PINX after 8 wk of short-day exposure. Control hamsters given 5-h MEL infusions, but not 10-h MEL or saline infusions, exhibited testicular growth and increased serum PRL levels. Hamsters with SCN lesions showed similar responses, regardless of the duration or type of infusion. Although the blockade of 10-h MEL infusion-induced testicular regression by SCN lesions in experiment 1 may have been due to stimulation of the testes by PRL, it is unlikely that the hyperprolactinemia accounted for the ability of SCN lesions to block effects of 10-h MEL infusions on fat pad and body weights. Therefore, the SCN and/or neighboring structures may participate in the response to short-day MEL signals in Siberian hamsters.
Yohimbine increases sympathetic nerve activity and norepinephrine spillover in normal volunteers
Authors: Grossman E. , Rea R. F. , Hoffman A. , Goldstein D. S.
Published: December 2017

It has been difficult to examine clinically the physiological role of central and peripheral alpha 2-adrenoceptors in humans. We simultaneously measured directly recorded peroneal skeletal muscle sympathoneural activity (MSNA) and the rate of appearance (spillover) of norepinephrine (NE) in forearm venous and arterial plasma before and at 15 min during intravenous administration of the alpha 2-blocker yohimbine (Yoh, 125 micrograms/kg bolus, 1 microgram.kg-1.min-1 infusion) in seven normal volunteers. Yoh administration increased mean arterial pressure by 16% (P less than 0.005), heart rate by 8% (P less than 0.05), and forearm vascular resistance by 67% (P less than 0.05). MSNA was increased by 73% (P less than 0.05), NE spillover into arterial blood by 125% (P less than 0.05), and forearm NE spillover (FSO) by 337% (P less than 0.005). Ganglion blockade by trimethaphan during Yoh infusion decreased MSNA to below detection limits and reversed Yoh-induced increases in arterial concentrations of NE and epinephrine. The results demonstrate that Yoh administration increases sympathoadrenal outflow. Because the mean increase of FSO was much larger than that of MSNA, the results suggest that alpha 2-adrenoceptors on sympathetic nerve endings modulate the neuronal release of NE for a given amount of sympathetic nerve traffic in humans; this effect seems prominent in the human limb.
Insulin-induced anestrus in Syrian hamsters
Authors: Wade G. N. , Schneider J. E. , Friedman M. I.
Published: December 2017

In Syrian hamsters, reproduction is sensitive to the availability of metabolic fuels. Estrous cycles can be interrupted by brief periods of food deprivation, by pharmacological inhibition of glycolysis and fatty acid oxidation, or by increasing energy demands for thermoregulation. We predicted that manipulations that divert an excessive portion of the metabolic fuel supply into storage also should inhibit reproduction. Redirection of metabolic fuels from oxidation to storage was accomplished by treatment with protamine zinc insulin suspension (PZI). Syrian hamsters treated with PZI and fed ad libitum increased their food intake by approximately equal to 40% and body fat stores, but there was no effect on estrous cycles. When PZI-treated hamsters were limited to approximately equal to 110% of their preinjection food intake, they still fattened, and there was a significant inhibition of estrous cyclicity. Thus, in the absence of overeating, PZI-enhanced energy storage may lead to a shortage of oxidizable metabolic fuels with the result that reproduction is inhibited in favor of processes essential for survival (e.g., cellular maintenance, thermoregulation). It is unlikely that insulin-induced anestrus is due to actions of PZI unrelated to metabolic fuel partitioning, because the hormone had no effects on estrous cyclicity in ad libitum-fed hamsters. These findings are inconsistent with the hypothesis that nutritional infertility is due to the failure to maintain a minimum body fat content and raise the possibility that the infertility associated with some types of obesity could be due in part to a disorder of macronutrient partitioning.
Effects of a peroxisome proliferator on beta-oxidation and overall energy balance in obese (fa/fa) rats
Authors: Assimacopoulos-Jeannet F. , Moinat M. , Muzzin P. , Colomb C. , Jeanrenaud B. , Girardier L. , Giacobino J. P. , Seydoux J.
Published: December 2017

The aim of the study was to examine in the obese Zucker (fa/fa) rats the effect of a peroxisome proliferator nafenopin on liver and brown adipose tissue peroxisomal and mitochondrial beta-oxidation enzyme activities and on the overall energy dissipation. A 17-day nafenopin treatment increased liver wet weight 2.1-fold and liver total acyl-CoA oxidase and mitochondria beta-oxidative activities 32- and 4.6-fold, respectively. It increased the interscapular brown adipose tissue (IBAT) acyl-CoA oxidase activity 2.1-fold but had no effect on the mitochondria beta-oxidative activity. Because nafenopin was found to decrease food intake by 22%, obese nafenopin-treated rats were compared with a group of obese pair-fed rats. Both food restriction and nafenopin treatment decreased body weight gain, but a decrease (14%) in fat content was only observed in nafenopin-treated rats. Food restriction of obese rats decreased the mean metabolic rate by 13%, and nafenopin treatment prevented this decrease. Both food restriction and nafenopin treatment decreased the mean daily respiratory quotient (RQ). However, the RQ of nafenopin-treated rats was steadily lower than that of control, whereas that of food-restricted rats was the same as that of control animals during the feeding period and decreased when food supply was exhausted. The increase in liver and IBAT fatty acid beta-oxidative activities may be the cause of the decreased lipid accretion measured in obese rats.
Effect of age on cold acclimation in rats: metabolic and behavioral responses
Authors: Owen T. L. , Spencer R. L. , Duckles S. P.
Published: December 2017

To determine whether senescence affects the metabolic and behavioral responses of rats to chronic cold exposure, 8- and 22-mo-old male Fischer 344 rats were studied before and after 6 wk of cold (6-10 degrees C) exposure. Measurements of body weight, food consumption, oxygen consumption, body temperature, and ambient temperature selection in a thermocline (7-37 degrees C linear gradient) were made at regular intervals throughout the acclimation period. Before acclimation, age groups differed significantly only by weight. During acclimation, older rats had increased mortality and morbidity below 10 degrees C. After acclimation at 10 degrees C, younger and older rats both selected cooler ambient temperatures (7 and 5 degrees C cooler than preacclimation, respectively), and older rats had a significantly greater decrease in body temperature in the thermocline. Both age groups increased resting metabolic rate at 25 degrees C with cold acclimation (16.5 and 10% increase for younger and older rats, respectively). This study indicates distinct differences in metabolic and behavioral responses of younger and older rats to cold acclimation. Chronic cold exposure is detrimental to thermoregulatory function in older rats, since it is not as effective in stimulating sustained increases in metabolic rate in older rats as in young adults and it leads to a preference for cooler ambient temperatures, resulting in increased heat loss and reduced body temperature.
Vascular tone influences arterial pressure lability after sinoaortic deafferentation
Authors: Jacob H. J. , Alper R. H. , Grosskreutz C. L. , Lewis S. J. , Brody M. J.
Published: December 2017

Sinoaortic deafferentation (SAD) results in increased variability of arterial pressure. The purpose of this study was to investigate the contribution of nonneurogenic, peripheral vasomotor mechanisms to this arterial pressure lability. In rats with SAD, ganglionic blockade combined with either captopril or a V1-vasopressin receptor antagonist reduced the high lability. Under these conditions, continuous infusions of phenylephrine and the endogenous vasoconstrictors angiotensin II, epinephrine, and vasopressin increased lability, suggesting that the level of vascular tone is important for maintaining lability. Hemodynamic changes in individual vascular beds did not correlate with pressure lability; however, the sum of the changes in resistance, an estimate of changes in total peripheral resistance, was significantly correlated. These results suggest that 1) direct actions of endogenous vasoconstrictors can induce marked variations of arterial pressure, presumably by sustaining a high background of vascular tone, and 2) variations in resistance of individual vascular beds do not account for the lability of arterial pressure evoked by infusion of vasoconstrictors. We conclude that vascular tone of neural and/or humoral origin is critical for the generation of fluctuations in arterial pressure associated with deafferentation of baroreceptors.
Altered sympathetic control of nutrient mobilization during physical exercise after lesions in the VMH
Authors: Balkan B. , Strubbe J. H. , Bruggink J. E. , Steffens A. B.
Published: December 2017

To study the impact of obesity on sympathetic nervous regulation of nutrient mobilization, obese rats and lean controls were subjected to physical exercise. Male Wistar rats, rendered obese by bilateral electrolytic lesions of the ventromedial hypothalamus (VMH) were subjected to 15 min swimming. Permanent cardiac catheters allowed frequent blood sampling. At rest, glucose, free fatty acids (FFA), and insulin concentrations were elevated in the obese animals, whereas catecholamine levels were similar in both groups. During exercise, glucose concentrations reached higher values in the lesioned rats, whereas these animals did not display the normal FFA increment. Plasma insulin concentrations were suppressed in both groups, and the rate of suppression was very similar when expressed as percentage change from resting levels. There was no difference in plasma epinephrine responses during swimming, but the increase in norepinephrine was diminished in the obese animals. The results suggest that obesity after VMH lesion leads to reduced stimulation of lipolysis by norepinephrine and a predominant mobilization of glucose during exercise, both favoring glucose utilization and the accumulation of fat.
FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms
Authors: Anderson B. O. , Bensard D. D. , Brown J. M. , Repine J. E. , Shanley P. F. , Leff J. A. , Terada L. S. , Banerjee A. , Harken A. H.
Published: December 2017

Bacterial lipopolysaccharide (LPS) and an N-formyl peptide, N-formyl-neoleucyl-leucyl-phenylalanine (FNLP), synergistically promote lung injury in rats as measured by 125I-labeled albumin flux. Concomitantly, neutrophils are sequestered in the lung. We hypothesized that LPS-FNLP-induced lung injury is mediated both by neutrophil-dependent and -independent mechanisms. Rats were depleted of circulating and marginating neutrophils with vinblastine. LPS-FNLP-induced lung protein leak was partially decreased in these neutrophil-depleted animals, although a component of lung injury remained. We hypothesized that LPS-FNLP-induced lung injury was also mediated by xanthine oxidase (XO). Rats were fed a tungsten-enriched diet that inactivates molybdenum-dependent oxidase systems. LPS-FNLP-induced lung leak was partially decreased in these animals as well. When tungsten-fed rats were also neutrophil depleted with vinblastine, no increase in 125I-albumin flux was observed in response to LPS-FNLP. In parallel experiments, lungs from vinblastine-pretreated rats were isolated and perfused. FNLP infusion into the LPS-primed, crystalloid-perfused lungs caused increased 125I-albumin flux, which was prevented by oxidase inhibition. We conclude that LPS-FNLP-induced lung injury is both neutrophil mediated and neutrophil independent. The nonneutrophil component of the LPS-FNLP-induced lung injury appears to be pulmonary XO derived and dependent.
Plasma glucagon, glucose, and free fatty acid concentrations and secretion during prolonged hypothermia in rats
Authors: Hoo-Paris R. , Jourdan M. L. , Moreau-Hansany C. , Wang L. C.
Published: December 2017

Impairment of metabolic substrate mobilization and utilization may be a factor limiting survival in hypothermia. Using a newly developed technique for maintaining stable low body temperature (Tb), substrate profiles and their regulation by glucagon were examined in hypothermic rats (Tb 19 +/- 0.3 degrees C) over 20 h. During cooling, plasma glucagon, glucose, and free fatty acid (FFA) concentrations increased significantly (536 +/- 55 pg/ml, 304 +/- 26 mg/100 ml, and 844 +/- 81 mueq/l, respectively). Plasma glucagon and glucose concentrations continued to increase up to 8 h (peaks 810 +/- 103 pg/ml and 451 +/- 33 mg/100 ml, respectively) and remained high throughout the rest of the hypothermic period. FFA concentrations decreased steadily during the hypothermic period. Exogenous glucagon (20 micrograms/kg) induced significant increases in plasma glucose (+129 +/- 31 mg/100 ml) and FFA concentrations (+351 mueq/l) at 2 h but had no effect at 15 h of hypothermia. In vitro evaluation of pancreatic alpha-cell function indicated that glucagon secretion is independent of temperature between 37 and 19 degrees C. Our data indicate that hypothermia is characterized by a disturbed substrate metabolism, which is likely due to an imbalance in pancreatic alpha- and beta-cell function and a time-dependent decrease in tissue sensitivity to glucagon. These deleterious changes may limit survival in hypothermia.
Exercise decreases fat selection in female rats during weight cycling
Authors: Gerardo-Gettens T. , Miller G. D. , Horwitz B. A. , McDonald R. B. , Brownell K. D. , Greenwood M. R. , Rodin J. , Stern J. S.
Published: December 2017

Weight cycling (weight loss and regain) increases fat intake in rats allowed to self-select a diet from protein, carbohydrate, and fat sources. This study reports the effects of exercise on macronutrient self-selection. Female Sprague-Dawley rats (5 mo old) self-selected their diet. After 3 wk, rats were assigned to one of the following three groups: ad libitum fed sedentary (Con), sedentary food restricted to 40% Con intake (R-Sed), or treadmill exercised (20 m/min, 1 h/day, 6 day/wk) food restricted to 40% Con intake (R-Ex). Food restriction was for 3 wk followed by 5 wk of refeeding. This was repeated for a second cycle. During restriction, body weight decreased by 30% in R-Sed and by 33% in R-Ex than in R-Sed, fat regain was greater in R-Sed. By week 3 of refeeding, total caloric consumption did not differ. However, fat selection increased in R-Sed (56% kcal) vs. R-Ex (30%) and Con (35%). Fat selection in R-Sed increased further during cycle 2 (73% kcal). Resting oxygen consumption decreased during food restriction in R-Sed and R-Ex. After refeeding, resting metabolic rate in R-Ex was significantly greater than in R-Sed. In conclusion, weight cycling increases dietary fat selection and adiposity. Exercise mitigates this effect.