bluuebunny/crossref_metadata_2025 huggingface dataset:
Properties of toad skin Na-K-ATPase with special reference to effect of temperature
Authors: Park YS , Hong SK
Published: December 2017

The NA-K-ATPase of toad skin was characteristically sensitive to Na, K, and ATP. It was not affected by amiloride, vasopressin, cAMP, and thyroxine, but stimulated by insulin. Ouabain, a potent inhibitor at 37 degrees C, did not inhibit the enzyme activity significantly at 23 degrees C. The optimal pH for the enzyme activity increased as temperature decreased. However, the optimal OH-/H+ ratio of the medium remained constant at 16 regardless of temperature. The Km for ATP remained unchanged between 37 and 8 degrees C if the OH-/H+ ratio was held constant at 16, but increased as temperature decreased if the pH of the medium was held constant at 7.4. The enzyme activity showed no appreciable variation between 37 and 20 degrees C with a constant OH-/H+ ratio of 16, whereas it decreased logarithmically at a constant pH of 7.4 over the same temperature range. These results indicate the presence of a typical Na-K-ATPase system in toad skin and that the enzyme is in the most active catalytic state at a fixed level of OH-/H+ ratio in the medium regardless of incubation temperature.
Effects of hypoxia on cardiac growth in neonatal rat
Authors: Hollenberg M , Honbo N , Samorodin AJ
Published: December 2017

To determine whether low oxygen environments enhance cardiac cell division in the neonatal period, newborn rat pups were reared for 21 days in 12-15% oxygen. Left ventricle and right ventricle weights were 30 and 180% greater than controls matched for body weight (P less than 0.001) as were left ventricle/body weight ratios (3.68+/-0.26 vs. 2.99+/-0.05 mg LV/g body wt,P less than 0.001). Left ventricular total DNA and DNA concentration was 95 and 48% greater than controls (P less than 0.001). Autoradiography confirmed that this increase in ventricular DNA resulted from an increased rate of division of cardiac muscle cells, fibroblast, and vascular endothelial cells. When [3H]thymidine was injected on day ), autoradiographs prepared on day 21 reflected an increased dilution of label in hypoxic rats consistent with enhanced proliferation. The labeling index and grains per nucleus of ventricular muscle cells was 25% (P less than 0.01) and 20% (P less than 0.02) less than controls, Thus, hypoxic stress applied early in the neonatal period augments the rate of division and ultimate number of cardiac muscle cells. Whether this enhancement results from a primary effect of oxygen or from secondary hemodynamic factors remains unknown.
Increase in resting tension of tracheal muscle due to rigor during metabolic inhibition
Authors: Bose D
Published: December 2017

Resting tension of canine tracheal smooth muscle increased when glucose and oxygen were withdrawn from the bathing medium. Similar treatment of muscle stimulated with carbachol caused first a relaxation and then a secondary increase in tension. The increase in tension due t0 metabolic inhibition, unlike normal tracheal contractions, was insensitive to calcium depletion, was not associated with an active state, and was accompanied by marked reduction of tissue adenosine triphosphate, creatine phosphate, and glycogen content. Because muscle stiffness was also increased we concluded that hypoxic glucose-free contracture is due to rigor and not to an increased tissue calcium level as has been previously suggested. Rigor shortening during lightly loaded isotonic conditions is better maintained than rigor tension during isometric conditions. Our results also indicate that rigor tension is reduced irreversibly on imposition of a load and, therefore, the load-extension relationship during rigor in smooth muscle should be studied by making only small load changes.
Inhibitory effect of ethacrynic acid on chloride permeability
Authors: Motais R , Cousin JL
Published: December 2017

Ethacrynic acid inhibits anion movements in ox red blood cells. The I50 for chloride is 7 X 10(-6) M. The inhibitory effect is instantaneous and completely reversed by washing the cells with a Ringer solution, suggesting that reaction with a membrane SH group is not involved in this process. Direct proof that ethacrynic acid does not act by its reactivity with thiol groups is given by experiments with dihydroethacrynic acid, a derivative that lacks the ability to combine with SH groups: the characteristics of inhibition are strictly identical (instantaneous and reversible; I50 equals 9 X 10(-6) M). All the phenoxyacetic derivatives tested were also more or less inhibitory. The relative activity of all the derivatives was highly correlated with their liposolubility, indicating that hydrophobic interaction is important in determining drug effect and influence of steric factors is minimal. The data suggest that inhibition essentially results from a hydrophobic interaction between ethacrynic acid and apolar regions of the membrane protein allowing chloride transport.
Rigor and resistance to stretch in vertebrate smooth muscle
Authors: Butler TM , Siegman MJ , Davies RE
Published: December 2017

Depletion of the APT content of the rabbit taenia coli muscle to 0.07 mumol/g caused an increase in force equal to 11% of maximum active tension (Po) when the muscle was bathed in a calcium-containing Krebs solution at 21 degrees C, but no increase in force in a calcium-free solution. Stimulation of the muscle in calcium-containing medium during the loss of ATP increased the force maintained and permitted demonstration of an increased stiffness by shortening of the muscle. There was no increase in resistance to stretch in the ATP-depleted state compared with the resting state. There was, however, a calcium-dependent resistance to stretch with properties that suggested the presence of attached crossbridges in the resting state. Bathing of the resting muscle in a calcium-free medium decreased the resting resistance to stretch and permitted demonstration of an increased resistance to stretch in the rigor state. It is concluded that the rigor state exists in vertebrate smooth muscle.
Effect of acetylcholine on Cl- and Na+ fluxes across dog tracheal epithelium in vitro
Authors: Marin MG , Davis B , Nadel JA
Published: December 2017

Electrical potential difference is generated across canine tracheal epithelium by active transport of Cl- toward and Na+ away from the lumen. The present study examines the effects of acetylcholine on short-circuit current, potential difference, resistance, and fluxes of 36Cl and 24Na measured across pieces of canine tracheal epithelium mounted in Ussing-type chambers. Under short-circuit conditions, acetylcholine (5 X 10(-5) M) increased significantly net ion flux toward the lumen of Cl- (n equals 7) from +1.7 +/- SE 0.5 TO +3.3 +/- SE 0.5 mueq/cm2 - h, and of Na+ (n equals 7) from -0.8 +/- SE 0.2 to +0.5 +/- SE 0.2 mueq/cm2 - h. Under open-circuit conditions, acetylcholine (5 X 10(-5) M) increased significantly the unidirectional flux of Cl- (n equals 6) toward the lumen from 4.7 +/- SE 1.3 to 5.9 +/- SE 1.4 mueq/cm2 - h, while the other measured fluxes did not change significantly, suggesting that net Cl- flux had increased toward the lumen. Atropine sulfate (10(-8) M) prevented the response to acetylcholine (5 X 10(-5) M). The increased ion flux due to acetylcholine may mediate water secretion into the airway lumen, and this secretion may have important effects on the physical properties of the liquid through which the respiratory cilia beat.
Absorption and exchange of water across rumen epithelium
Authors: Dobson A , Sellers AF , Gatewood VH
Published: December 2017

The osmotic pressure of solutions in the ventral sac of the rumen of the conscious cow was varied with Na Cl or mannitol. The mucosal blood flow measured by HTO clearance was minimal when the lumen contained an isotonic solution and rose threefold when the rumen was hypo- or hypertonic to plasma by 150 mosmol/kg. Thus osmotic gradients actoss the rumen epithelium stimulated mucosal blood flow. Using osmotic gradients small enough to avoid blood flow stimulation, the net water flow could be enhanced by butyrate, a chemical stimulator of blood flow. Thus water movement was partially limited by blood flow. This implied an appreciable change in osmotic pressure of the capillary blood toward that of the rumen contents. The relative importance of blood flow, membrane permeability, and solute uptake on water transport was assessed. The osmotic pressure in the rumen was stationary when the rumen solution was distinctly hypotonic to plasma. The absorbate in the absence of an osmotic gradient was thus hypertonic. The net uptake of solute increased rapidly when the solution in the lumen was hypertonic to plasma. This gave rise to a more rapid rate of change of osmotic pressure in the rumen under this condition.
Tumor necrosis factor-alpha decreases surfactant protein B mRNA in murine lung
Authors: Pryhuber G. S. , Bachurski C. , Hirsch R. , Bacon A. , Whitsett J. A.
Published: December 2017

Respiratory failure secondary to acute lung inflammation is associated with quantitative and qualitative abnormalities of pulmonary surfactant. The surfactant-associated proteins (SP)-A, -B, and -C are critical for normal surfactant function, synthesis, and metabolism.Tumor necrosis factor-alpha (TNF-alpha), a primary mediator of acute lung inflammation, decreased SP gene expression in vitro (32, 34). In the present in vivo study, transient T cell activation and TNF-alpha release were initiated by intraperitoneal administration of anti-CD3 antibody 145-2C11. Serum TNF-alpha was elevated 2 h after injection of the antibody. SP-B and -C mRNA were decreased 12 and 24 h after antibody treatment. Intratracheal murine TNF-alpha also resulted in decreased SP-B and SP-C mRNA levels in the bronchiolar and alveolar epithelium of adult FVB/N mice, as demonstrated by S1 nuclease protection and in situ hybridization assays, despite minimal histological inflammation. SP-A mRNA was not significantly altered after anti-CD3 antibody and was only mildly decreased after TNF-alpha. As previously reported, intercellular adhesion molecule-1 mRNA was elevated after intratracheal TNF-alpha. SP insufficiency contributes to the pathogenesis of pulmonary diseases associated with increased TNF-alpha, such as adult respiratory distress syndrome and pneumonia (8). TNF-alpha-mediated decrease in SP gene expression may contribute to the surfactant dysfunction and atelectasis observed in inflammatory lung diseases.
Acetylcholine in isolated airways of rat, guinea pig, and human: species differences in role of airway mucosa
Authors: Reinheimer T. , Bernedo P. , Klapproth H. , Oelert H. , Zeiske B. , Racke K. , Wessler I.
Published: December 2017

Stored endogenous acetylcholine (ACh) and in vitro synthesis of [3H]ACh were measured in isolated, mucosa-intact and mucosa-denuded airways of rat, guinea pig, and humans. In addition, choline acetyltransferase (ChAT) activity and ACh content were measured in freshly isolated airway mucosa as well as in cultured epithelial cells of rat tracheas. Rat tracheas stored 25 nmol/g ACh, whereas guinea pig tracheas and human bronchi contained only 2-3 nmol/g ACh. When incubated with [3H]choline, the isolated airways of rat, guinea pig, and human synthesized significant amounts of [3H]ACh. In guinea pig and human airways, removal of the mucosa affected neither stored ACh nor in vitro synthesis of [3H]ACh. In rat tracheas, however, removal of the mucosa resulted in a 50% reduction of stored ACh. Freshly isolated mucosa wiped off from the luminal surface of rat tracheas contained large amounts of ACh (6.5 nmol/g airway), whereas in human mucosa (central bronchi) only small amounts of ACh were found. In enzymatically isolated mucosal cells of rat tracheas, a considerable ChAT activity (21 nmol.mg protein 1.h-1) was detected, blockable by bromoacetylcholine. Enzymatically isolated human mucosa contained a rather low ChAT-like activity (0.5 nmol.mg protein 1.h-1), not sensitive to bromoacetylcholine. In cultured epithelial cells of rat tracheas (4th-6th passage), neither ChAT activity nor ACh was detected. The large airways of rat, guinea pig, and humans contain considerable amounts of ACh, supporting histological evidence of a dense cholinergic innervation, particularly of rat tracheas. The mucosa of rat tracheas synthesizes and stores large amounts of ACh, whereas the low ChAT activity in human mucosa argues against the presence of cholinergic neurons able to synthesize and store ACh.
Dual signal transduction mechanisms modulate ciliary beat frequency in upper airway epithelium
Authors: Yang B. , Schlosser R. J. , McCaffrey T. V.
Published: December 2017

This study investigated the effects of methacholine and terbutaline on the ciliary beat frequency (CBF) of upper airway epithelium. The CBF of cultured human adenoid explants was measured using microphotometry. Methacholine (10(-6) M) and terbutaline (10(-6)M) increased CBF a maximum of 23.0 +/- 1.8% (P < 0.001) and 16.5 +/- 2.3% (P < 0.001). Inhibition of endogenous nitric oxide (NO) production by nitro-L-arginine methyl ester (L-NAME) (10(-6) M) abolished the effects of methacholine in L-arginine-free medium (P < 0.008). This inhibition was reversed by addition of L-arginine. There was no inhibition of terbutaline-induced ciliostimulation by L-NAME (P < 0.5). KT-5823 (10(-6)M), a guanosine 3',5'-cyclic monophosphate (cGMP) kinase inhibitor, significantly inhibited the effects of methacholine (P < 0.0001), but not terbutaline (P > 0.15). H-89 (10(-6) M), a cAMP kinase inhibitor, significantly inhibited terbutaline-induced ciliostimulation (P < 0.0001), but not methacholine-induced ciliostimulation (P > 0.05). Diclofenac (10(-6) M), a cyclooxygenase inhibitor, significantly inhibited the effects of methacholine (P < 0.0007) but had no effect on terbutaline-induced ciliostimulation (P > 0.05). These findings suggest that the CBF of upper airway epithelium is modulated through at least two distinct pathways. The beta 2-adrenoceptor produces ciliary stimulation by a pathway involving increased intracellular cAMP levels, while the muscarinic receptor increases CBF by a mechanism involving production of prostaglandins, NO, and cGMP.
Acetylcholine and caffeine activate Cl- and suppress K+ conductances in human bronchial smooth muscle
Authors: Janssen L. J.
Published: December 2017

The conductance changes underlying agonist-evoked depolarization in human airway smooth muscle (ASM) were examined using single ASM cells liberated enzymatically from noncarcinomatous bronchi and studied using patch-clamp techniques. Step commands to potentials at or more positive than the resting membrane potential evoked outward current, which was predominantly delayed rectifier K+ current with some Ca(2+)-dependent K+ current Caffeine (5 mM) evoked depolarization and contraction lasting several minutes. During voltage clamp at -60 mV, caffeine evoked inward current with a latency of approximately equal to 1 s, mean amplitude of 320 +/- 65 pA, and a duration of approximately equal to 5 s (even though agonist application exceeded this duration). With the use of the perforated-path configuration, these responses could be evoked repeatedly at 4-min intervals for up to 30 min; rupture of the membrane and dialysis of the cytosol, however, abrogated the responses to caffeine. The current was outwardly rectifying with mean reversal potential (Vrev) of -31 +/- 4 mV. When K+ conductances were blocked by Ca+, the current-voltage (I-V) relationship was linear (i.e., an outwardly-rectifying component was eliminated) and Vrev was displaced in the positive direction to +2 +/- 1 mV. Changes in the CL- equilibrium potential were accompanied by a displacement of Vrev in a manner predicted by the Nernst equation for a Cl- current. The effects of caffeine were mimicked by acetylcholine; in addition, acetylcholine and caffeine each occluded the response to the other agonist. Spasmogens also caused a prolonged suppression of K+ currents (both Ca(2+)--dependent and delayed rectifier). We conclude that, in human ASM, acetylcholine and caffeine cause a transient activation of Ca(2+)--dependent Cl- current (due to release of internal Ca2+) and prolonged suppression of K+ currents, leading to depolarization and contraction.
Depletion of alveolar macrophages decreases neutrophil chemotaxis to Pseudomonas airspace infections
Authors: Hashimoto S. , Pittet J. F. , Hong K. , Folkesson H. , Bagby G. , Kobzik L. , Frevert C. , Watanabe K. , Tsurufuji S. , Wiener-Kronish J.
Published: December 2017

The mechanism for neutrophil (PMN) influx into infected airspaces of the lung is not known. To determine whether alveolar macrophage products are important in the initiation of chemotaxis, we depleted rats of alveolar macrophages by aerosolizing negatively charged oligolamellar liposomes complexed to clodronate disodium. Ninety-five percent of the alveolar macrophages were depleted, and lung injury and inflammation were minimized with this depletion technique. Rats depleted of alveolar macrophages were then anesthetized, and either 5 x 10(6) colony-forming units (CFU) or 5 x 10(7) CFU of Pseudomonas aeruginosa were instilled into the airspaces of these animals. When recombinant macrophage inflammatory protein MIP-2 was intratracheally instilled into rats depleted of alveolar macrophages, PMN were recruited to their airspaces. Nonetheless, PMN numbers were decreased in the lavage fluids when moderate or large inoculums of bacteria were instilled into depleted rats, although the PMN response appeared dose dependent. Levels of bioactive tumor necrosis factor-alpha and immunoreactive proteins CINC/gro (cytokine-induced PMN chemoattractant) in the lavage fluids obtained from infected rats depleted of alveolar macrophages were significantly decreased compared with the levels in the lavage fluids obtained from normal infected rats. MIP-2 mRNA expression, as detected by Northern analysis, was also decreased in the infected lungs of depleted rats, and the lavage fluid from these rats had significantly decreased chemotactic activity. Therefore these results suggest that alveolar macrophage products play a direct role in the initial recruitment of PMN into infected lungs.
Cellular and subcellular localizations of annexins I, IV, and VI in lung epithelia
Authors: Mayran N. , Traverso V. , Maroux S. , Massey-Harroche D.
Published: December 2017

The cellular and subcellular localizations of annexins I, IV, and VI in the rabbit tracheal and alveolar epithelia were studied by performing immunofluorescence labeling on thin frozen sections of these tissues, using specific monoclonal antibodies. Annexin I was highly expressed by ciliated cells, where it was concentrated in the cilia but was also present along the basolateral domain of the plasma membrane and in the nuclei. It was also abundant in the cytoplasm of type II pneumocytes and alveolar macrophages. Either one or both of these alveolar cells might be capable of secreting a very small amount of annexin I, which was found to be associated with the surfactant layer. Annexin IV was synthesized by all the lung epithelial cells. It was associated with the plasma membrane basolateral domain in ciliated cells and with either the apical or basal domain of plasma membrane in type I pneumocytes, whereas it was cytoplasmic in goblet cells and type II pneumocytes. Annexin VI was expressed only by alveolar endothelial cells, where it was probably cytoplasmic. None of these three annexins seem to be expressed in the nondifferentiated tracheal basal epithelial cells.
Posttranscriptional regulation of plasminogen activator inhibitor-1 in human lung carcinoma cells in vitro
Authors: Shetty Sreerama , Idell Steven
Published: December 2017

Plasminogen activator inhibitor-1 (PAI-1), the major circulating inhibitor of urokinase [urokinase-type plasminogen activator (uPA)], has been linked to the pathogenesis of lung cancer. PAI-1 belongs to the serpin family of inhibitors and inhibits both free urokinase (uPA) and receptor-bound urokinase (uPA receptor). Although PAI-1 has been related to a poor prognosis in lung carcinoma, mechanisms that regulate its expression in human lung cancer cells are not well understood. We used cultured human small cell and non-small cell lung carcinoma cell lines as model systems to elucidate the regulatory mechanisms that control expression of PAI-1. Levels of PAI-1 protein were significantly increased in selected lung carcinoma cells compared with those in normal small-airway epithelial cells. Corresponding steady-state levels of PAI-1 mRNA were similarly increased in these cells. The half-life of PAI-1 mRNA was prolonged in these lung carcinoma cell lines after transcriptional or translational blockade. We identified a 60-kDa protein that binds the 3′-untranslated region of PAI-1, and complex formation of this binding protein with PAI-1 mRNA reciprocally correlates with mRNA stability. The findings demonstrate that expression of PAI-1 is regulated at the posttranscriptional level in small cell- and non-small cell-derived human lung carcinoma cell lines. Altered regulation of PAI-1 at the posttranscriptional level may contribute to relative overexpression by malignant lung epithelial cells. A newly identified regulatory protein that binds to the 3′-untranslated region of PAI-1 mRNA appears to be involved in the posttranscriptional regulation of PAI-1 gene expression by human lung carcinoma cells in vitro.
Acid-base balance and plasma composition in the aestivating lungfish (Protopterus)
Authors: DeLaney R. G. , Lahiri S. , Hamilton R. , Fishman P.
Published: December 2017

Upon entering into aestivation, Protopterus aethiopicus develops a respiratory acidosis. A slow compensatory increase in plasma bicarbonate suffices only to partially restore arterial pH toward normal. The cessation of water intake from the start of aestivation results in hemoconcentration and marked oliguria. The concentrations of most plasma constituents continue to increase progressively, and the electrolyte ratios change. The increase in urea concentration is disproportionately high for the degree of dehydration and constitutes an increasing fraction of total plasma osmolality. Acid-base and electrolyte balance do not reach a new equilibrium within 1 yr in the cocoon.
Properties of the laryngeal chemoreflex in neonatal piglets
Authors: Lee J. C. , Stoll B. J. , Downing S. E.
Published: December 2017

Cardiorespiratory reflex responses to laryngeal chemoreceptor stimulation were studied in 62 piglets of both sexes varying in age from 1 to 79 days. The distal trachea was cannulated to provide a free airway and the proximal end used to introduce fluids into the laryngeal area. Introduction of either water or milk produced apnea, bradycardia, and hypertension. Swab application of test fluids to the laryngeal epithelium produced similar responses. The reflex could be interrupted by flushing the laryngeal region with saline, by cutting the superior laryngeal nerves (SLN) or by anesthetizing the laryngeal epithelium with lidocaine. Electrical stimulation of SLN elicited identical responses. Respiratory inhibition by the reflex was enhanced following central depression with chloralose and overridden by administration of the respiratory stimulant, aminophylline. The relative potency of the laryngeal reflex was estimated to be equivalent to about 40% of the dose of chloralose which produced permanent respiratory arrest. It is concluded that in circumstances where respiratory drive is reduced the laryngeal inhibitory reflex is capable of caused persistent apnea and asphyxial death in the young piglet.
Ingestive behavior after intracerebral and intracerebroventricular infusions of glucose and 2-deoxy-D-glucose
Authors: Berthoud H. R. , Mogenson G. J.
Published: December 2017

Direct infusions of 2-DG into the lateral hypothalamic area (LHA), the ventromedial hypothalamus (VMH), the dorsal hippocampus, the amygdaloid complex or the caudate nucleus were all ineffective in eliciting drinking or feeding in satiated rats. However, 2-DG (but not D-glucose) infused into the lateral ventricles of satiated rats elicited feeding preceded by an initial burst of drinking, which could be blocked by prior intraventricular infusion of the alpha-adrenergic antagonist, phentolamine, by the serotonergic blocker, methysergide, but only slightly by the dopaminergic receptor blocker, spiroperidol. The feeding response was totally blocked by phentolamine but not by methysergide or spiroperidol. These results show that 1) intraventricular administration of 2-DG can induce feeding, as well as drinking, supporting the hypothesis of cerebral glucoreceptors for the initiation of feeding behavior; and 2) local cytoglucopenia in the LHA, the VMH, or other limbic structures is not sufficient to initiate feeding. It is hypothesized that a specific pattern of cerebral glucoprivation rather than local glucoprivation, or an action of 2-DG on the presynaptic membrane of noradrenergic "feeding neurons" could be the mechanisms of 2-DG-induced feeding.
Essential role of mean circulatory filling pressure in salt-induced hypertension
Authors: Manning R. D. , Coleman T. G. , Guyton A. C. , Norman R. A. , McCaa R. E.
Published: December 2017

Experimental hypertension was produced in nine dogs by continuously infusing isotonic saline after renal mass had been surgically reduced to approximately 30% normal. Data were collected during 8 days of base-line measurements and 13 days of saline infusion to determine the cause of the initial increase in cardiac output observed in this type of hypertension and to measure other variables possibly important in the pathogenesis of hypertension. During the infusion period, these dogs demonstrated an increase in arterial pressure to hypertensive levels, transient increases in blood volume, sodium space, and cardiac output, initially depressed then subsequently elevated total peripheral resistance, and decreases in plasma renin activity and plasma aldosterone concentration. The mean circulatory filling pressure increased 4.7 Torr by day 3 and was still elevated 2 Torr at the end of the 2nd wk of infusion. We conclude that the initial increase in cardiac output in salt-loading hypertension is due to elevated fluid volumes and the associated increase in mean circulatory filling pressure.
Modes of thermal protection in polar bear cubs--at birth and on emergence from the den
Authors: Blix A. S. , Lentfer J. W.
Published: December 2017

At birth in late December the polar bear is small (700 g), uninsulated, and helpless. It probably has a modest capacity for metabolic heat production and depends on the female and a snow den in which it is born for thermal protection. The microclimate of an artificial polar bear den was investigated at Point Barrow, AK, and the temperature therein found to stay around 0 degrees C provided a heat source (200 W) equivalent to an adult polar bear was introduced. When the bears desert the den in early April the cub has grown to about 10 kg and has a well-developed fur insulation, but almost no subcutaneous fat. The cub has a high resting metabolic rate (4.6 W.kg-1), which is supported by the fat polar bear milk. Its lower critical temperature is about -30 degrees C, and an ambient temperature of -45 degrees C results in only a 33% increase in metabolism. The cub can tolerate a wind chill of 2.3 kW.m2 without apparent stress of drop in rectal temperature. If the cub is immersed in ice water rectal temperature drops 11 degrees C in 30 min. It is concluded that the cub can tolerate extremely low temperatures in air due to fur insulation and high metabolic heat production, but is unable to cope with the chill of ice water for any prolonged period of time.
Circadian control of thermoregulation in the squirrel monkey, Saimiri sciureus
Authors: Fuller C. A. , Sulzman F. M. , Moore-Ede M. C.
Published: December 2017

The characteristics and control of the circadian rhythms of core body temperature (colonic) and skin temperature (tail) were studied in chair-acclimatized squirrel monkeys (Saimiri sciureus). When animals were entrained to a light-dark cycle (12 h 600 lx; 12 h less than 1 lx) these two temperatures displayed prominent, reproducible, tightly coupled circadian rhythms. In contsant light of 600 lx, where no other effective circadian time cues were present, both temperature rhythms persisted with free-running periods. Within each animal, however, these rhythms were not as tightly coupled to one another as in LD. On occasion colonic and tail temperature rhythms free-ran with different circadian periods and some animals demonstrated "splitting" of the colonic temperature rhythm, with the colonic temperature rhythm displaying a bimodal pattern. These results suggest that the circadian rhythm of body temperature in primates is under the control of more than one potentially independent circadian oscillator.
Computer simulation of metabolism in pyruvate-perfused rat heart. III. Pyruvate dehydrogenase
Authors: Kohn M. C. , Achs M. J. , Garfinkel D.
Published: December 2017

A physiologically and biochemically realistic model of the regulation of pyruvate dehydrogenase complex (PDH) was constructed for the perfused rat heart. It includes conversion between inactive (phospho) and active (dephospho) forms by a specific protein kinase (PDHK) and phosphoprotein phosphatase (PDHP). The activity of the tightly bound PDHK is influenced by synergistic activation/inhibition by acetyl CoA/CoASH and NADH/NAD. PDHK in this simulation was more sensitive to the fraction of ADP that was Mg2+-chelated than to the ATP-to-ADP ratio. Ca2+ stimulates binding of Mg2+-dependent PDHP to the complex; the bound enzyme was considered to be the active species. The fraction of PDH in the active form, rather than substrate and inhibitor levels, determines PDH activity under these conditions. This fraction depends on the present value and recent history of the difference between PDHK and PDHP activities. Both of these are active continuously and continuously control PDH.
Sinovagal interaction in arterial pressure restoration after 10% hemorrhage
Authors: Hosomi H. , Sagawa K.
Published: December 2017

The summation between the carotid sinus baroreceptor reflex system (CS system) and the vagally mediated reflex system (V system) was studied as they restore mean arterial pressure (MAP) after 10% quick hemorrhage in splenectomized conscious dogs chronically instrumented with catheters for pressure measurement and hemorrhage. The experiment was repeated under nerve-intact condition (intact), with cold block of the vagi ([V]), after carotid sinus denervation (CS), and CS plus [V] situations. MAP falls at 1.5 min after the hemorrhage were 7.2 in intact, 24.7 in [V], 36.0 in CS, and 67.6 in CS + [V] mmHg. When we calculated the open-loop gains of CS and V systems assuming a simply additive summation between them a self-contradiction occurred. To avoid this contradiction, it was necessary to assume that CS and V systems interact in a facilitatory manner. Mean open-loop gains calculated under this assumption were 1.64 for the CS system alone, 0.89 for the V system alone, and 6.59 for the interacting component between them. These intriguing results warrant further analysis of the summation between the two reflex systems.
Metabolism of totally ischemic excised dog heart I. Construction of a computer model
Authors: Achs Murray J. , Garfinkel David
Published: December 2017

Construction and fit to the experimental data of a computer model of glycolysis, the Krebs cycle, and related metabolism in an ischemic dog heart preparation, involving 122 metabolites, 65 enzymes, and 406 chemical reactions, is described. The experimental preparation simulated is a dog heart excised from the body, placed in a beaker of Tyrode's solution, and sampled for 100 min; the model required only moderate modification from models representing perfused rat hearts, and little modification from a model of another ischemic dog heart preparation. Common underlying mechanisms for the ischemia are indicated, although this preparation appears to evolve more slowly with time, perhaps owing to heavy sedation and diffusion-limited transport. Lactate is, at first, exported and then accumulates intracellularly; pH falls, but not as much in the mitochondria as the cytoplasm; redox couples go reduced, but with counterintuitive time courses; calcium phosphate is calculated to precipitate, as often observed in cardiac ischemia

enzymes; glycolysis; simulation; metabolic regulation

Submitted on October 24, 1978

Accepted on May 21, 1979
Fish gill carbonic anhydrase: acid-base regulation or salt transport?
Authors: Haswell M. S. , Randall D. J. , Perry S. F.
Published: December 2017

During the passage of blood through the fish gill, large oscillations in oxygen and carbon dioxide content occur. Although the increase in oxygen content is related to oxygen binding by red blood cells, the fall in carbon dioxide content is independent of red blood cells and their complement of carbonic anhydrase. This loss of venous carbon dioxide content is primarily the result of the movement of plasma bicarbonate into the gill epithelium, where it subsequently can be converted to molecular carbon dioxide by branchial carbonic anhydrase. The ultimate control of the bicarbonate flux and hence plasma hydrogen ion regulation is coupled to salt movements also occurring in the fish gill. This evidence in conjunction with carbonic anhydrase localization studies makes it possible to formulate a model capable of explaining acid-base regulation as well as salt transport in freshwater- or seawater-adapted fish. In light of this model the role of the “chloride cell” is discussed.
Thermoregulation in the only nocturnal simian: the night monkey Aotus trivirgatus
Authors: Le Maho Y. , Goffart M. , Rochas A. , Felbabel H. , Chatonnet J.
Published: December 2017

The night monkey, a tropical monkey, is the only nocturnal simian; its thermoregulation was studied for comparison with other nocturnal or diurnal primates and other tropical mammals. Resting metabolic rate was 2.6 W (closed-circuit method) and 2.8 W (open-circuit method), 24 and 18% below the value predicted from body mass. The thermoneutral zone was very narrow; the lower critical temperature (LCT) was 28 degrees C and the upper critical temperature (UCT) was 30 degrees C. The body temperature (Tb) was at its minimum (38 degrees C) at an ambient temperature (Ta) of 25 degrees C, thus below the LCT. At low Ta, the increase in metabolic rate (MR) was smaller than predicted by the Scholander model, since MR intersected to a Ta 13 degrees C above Tb when extrapolated to MR = 0; this was attributed to a decrease of body surface area by behavior. The thermal conductance at the LCT was low: 2.3 W . m-2 . degrees C-1. Above the UCT, panting was the major avenue of heat loss. The response pattern of nocturnal habits, low resting metabolic rate, low thermal conductance, and panting in the night monkey, unique among simians, is found in many other mammals of tropical and hot desert habitats; it may be considered as an alternative adaptation to the thermal environment.
Control of glomerular filtration rate by circulating angiotensin II
Authors: Hall J. E. , Coleman T. G. , Guyton A. C. , Kastner P. R. , Granger J. P.
Published: December 2017

Previous studies from our laboratory have provided evidence that the renin-angiotensin system plays an important role in controlling glomerular filtration rate (GFR) through an efferent arteriolar vasoconstrictor mechanism; however, the relative importance of circulating versus intrarenally formed angiotensin II (ANG II) in this control has not been determined. In the present study, the role of circulating ANG II in regulating GFR during reduced renal artery pressure (RAP) was examined in sodium-depleted dogs. After 90 min of infusion of the angiotensin-converting enzyme inhibitor SQ 14225, which presumably inhibited formation of both circulating and intrarenal ANG II, reduction of RAP to 81 +/- 2 mmHg resulted in marked decreases in GFR, filtration fraction (FF), and calculated efferent arteriolar resistance (RE), whereas renal blood flow (RBF) was maintained approximately 40% above initial control levels determined before SQ 14225 infusion. Replacement of circulating ANG II during SQ 14225 infusion, by intravenous infusion of ANG II at rates that decreased RBF to control levels, increased GFR, FF, and RE to levels not significantly different from control while RAP was maintained constant by aortic constriction. These observations suggest that circulating ANG II plays an important role in regulating RE and GFR during reductions in RAP. The importance of intrarenally formed ANG II in controlling GFR remains to be determined.
Shivering thermogenesis and glucose uptake by muscles of normal or diabetic rats
Authors: Smith O. L. , Davidson S. B.
Published: December 2017

Acute cold exposure of normal rats (4 degrees C for 24 h) increased food intake, reduced plasma glucose and liver glycogen, caused a small increase in plasma free fatty acids, and lowered serum insulin concentration by 50%. In fasted rats, cold raised fatty acid levels twice as high as in fed. In mild diabetes (40 mg/kg streptozotocin iv) cold reduced glucose levels in blood and urine, but in severe diabetes (90 mg/kg) cold aggravated hyperglycemia and ketonuria. Changes in muscle glucose utilization were also studied, after evisceration (functional hepatectomy) of rats from each group. Uptake was calculated from the fall in plasma glucose concentration during the 4-h period after a load of 50% glucose iv. Cold normally increased uptake 67%, but it failed to do so in fasted rats. In diabetic rats, cold enhanced uptake, but only if the disease were mild or insulin controlled. Sensitivity of uptake to insulin was unaffected by cold. The results suggest that shivering thermogenesis, like exercise, can promote glucose uptake by skeletal muscle, if enough insulin is present to prevent excess mobilization of lipid substrates.
Dietary-induced severe obesity: a rat model
Authors: Oscai L. B.
Published: December 2017

In this study, dietary intervention before and after weaning was used to produce body fatness in adult rats ranging from severe obesity (61% body fat) to the lean condition (18% body fat). To produce severe obesity, rats were programmed for a high caloric intake during suckling. After weaning, they were provided unrestricted access to a diet in which approximately 40% of the calories were derived from fat (high-fat diet). The high-fat diet appeared to cause hyperphagia such that appetites were highly stimulated between 29 and 58 wk of age. Body weight in these rats stabilized at 1,213 +/- 62 g. Severe obesity was also observed in rats programmed for a low caloric intake if, after weaning, they ate the high-fat diet (59% body fat). These results provide evidence that the fat content of the diet may play a regulatory role in the development of severe obesity.
Glucocorticosteroid injection is a circadian zeitgeber in the laboratory rat
Authors: Horseman N. D. , Ehret C. F.
Published: December 2017

Intraperitoneal temperatures were monitored by radiotelemetry to observe the thermoregulatory rhythm of male laboratory rats (Rattus norvegicus albinus) Rats received single injections of dexamethasone (as dexamethasone sodium phosphate) during constant darkness (0.1 lx) with food freely available or no food available. No phase shifts occurred following saline injection or dexamethasone at 1 mg/kg body wt. Depending on the phase of injection relative to the circadian cycle, dexamethasone at 10 mg/kg caused thermoregulatory peaks to be either delayed or advanced on the 4th and 5th day after injection. There was an insensitive interval which corresponded to subjective day. Phase shifts induced by dexamethasone during ad libitum feeding were of less magnitude than those induced during starvation. The determination of phase-shifting parameters (i.e., a phase-response curve) for hormonal substances represents a rigorous and broadly applicable technique for determining endogenous mechanisms for circadian phase control and entrainment.
Ionic distribution in dopamine-stimulated NaCl fluid-secreting cockroach salivary glands
Authors: Gupta B. L. , Hall T. A.
Published: December 2017

The compound, racemose, innervated salivary glands of the cockroach Periplaneta americana closely resemble in structure and function the mammalian salivary glands (C.R. House, Biol. Rev. 55: 417-473, 1980). The quantitative distribution of Na, K, Cl, Ca, Mg, P, and S was investigated in the P-cells secreting isotonic NaCl and in duct lumens by using electron probe X-ray microanalysis of frozen-hydrated and frozen-dried cryosections. In the unstimulated glands in vitro the cells had (mmol/l cell-H2O) Na, 10; K, 110; Cl, 39 while the primary saliva had Na, 153; K, 4; Cl, 151. With 1 mumol dopamine in the bathing Ringer solution the P-cells had Na, 25; K, 177; Cl, 58 and the primary saliva, Na, 153; K, 26; Cl, 172. During passage through the ducts, the primary saliva was modified by an absorption of NaCl: more in unstimulated than in stimulated glands. It is proposed that the cells have a Na-K-ATPase both in the apical and basal cell membrane, as in vertebrate choroid plexus, and dopamine might increase the K and Na conductance of the basal cell membrane.
Brain and CSF water and ions during dilutional and isosmotic hyponatremia in the rat
Authors: Melton J. E. , Nattie E. E.
Published: December 2017

Dilutional (DH) and isosmotic (IH) hyponatremia (plasma [Na+] = 103-109 meq/l) were produced in conscious rats over 3-6 h by intraperitoneal injection of water or mannitol Ringer solution. During DH, CSF [Na+], [Cl-], and osmolality decreased as predicted by passive dilution by the water load. During IH, these variables exhibited little change. Brain water was unchanged during IH despite significant reduction of brain Na+ and Cl- content suggesting that tissue ions lost were replaced by other osmoles. During DH, brain water increased but less than predicted by passive osmotic equilibration. Cell volume increased as predicted by passive swelling while the extracellular volume (Cl space) decreased. Tissue K+ content decreased by a small but significant amount. Tissue Na+ and Cl- decreased by 21 and 28%. This pattern of fluid compartmental and electrolyte changes suggests that brain volume regulation during acute DH occurs via reduction of extracellular volume as cells swell. This may result from bulk flow of extracellular fluid to CSF or from ion and water movement across the blood-brain barrier.
A mathematics for physiology
Authors: Garfinkel A.
Published: December 2017

Nonlinear dynamics gives us a language within which to express the basic concepts of physiology. Form, qualitative change, oscillation, stability, and other biologically important notions find natural expressions in this new mathematical approach. An introduction to qualitative dynamics is sketched, its relevance to physiology is argued, and several examples of its usefulness in providing models and metaphors for describing brain activity are offered.
Esophageal desalination of seawater in flounder: role of active sodium transport
Authors: Parmelee J. T. , Renfro J. L.
Published: December 2017

The esophagus of the flounder, Pseudopleuronectes americanus, was studied to determine how salinity of ingested seawater (SW) is decreased before fluid absorption in the intestine. Drinking rate was 2.5 ml X h-1 X kg-1. Stomach fluid osmolality was 45% that of seawater, and intestinal fluid was isosmotic to plasma. Esophagus and stomach were nearly impermeable to 28Mg; thus Mg concentrations were accurate indicators of fluid addition and NaCl removal between pharynx and stomach. Measurements of water and ion fluxes across isolated esophageal epithelium mounted in Ussing chambers and bathed by Ringer solution showed that the tritiated water flux was lower in esophagus than in intestine and that 22Na flux ratio was 1.4 (Jm leads to s/Js leads to m) regardless of acclimation medium (100 or 10% SW). Potential difference was zero, and electrical resistance averaged 90 omega X cm2. Mucosal-to-serosal Na transport was inhibited by 0.1 mM amiloride, 0.1 mM ouabain, and Cl-free medium, whereas 1.0 mM furosemide had no effect. Net esophageal Na absorption (mucosal-to-serosal) averaged 10.0 mumol X h-1 X cm-2 with mucosa exposed to SW and was inhibited 46% by 0.1 mM ouabain. Taken together the above observations suggest a role for both passive and active esophageal Na transport in SW desalination.
Vagotomy does not alter cholecystokinin's inhibition of sham feeding
Authors: Kraly F. S.
Published: December 2017

Verified bilateral abdominal vagotomy (with hepatic branch intact) did not alter the ability of 20% pure cholecystokinin (CCK) or octapeptide of cholecystokinin (CCK-8) to inhibit sham feeding of liquid diet in dose-response studies for male Sprague-Dawley rats with open gastric fistula. In light of previous reports that 1) abdominal vagotomy blocks the satiety effect of exogenous CCK-8 on real feeding in intact rats and 2) inhibition of sham feeding requires seemingly supraphysiological doses of exogenous CCK or CCK-8, these findings show that the inhibition of sham feeding by CCK and the inhibition of real feeding by CCK are different. This limits the utility of the sham-feeding preparation for examining mechanisms for the satiety action of CCK.
What is a biological oscillator?
Authors: Friesen W. O. , Block G. D.
Published: December 2017

Biological oscillators are amenable to qualitative analysis even before they have been described exhaustively in quantitative terms. Qualitative analysis can identify the elements essential for generating the oscillations and can enhance our understanding of underlying oscillator mechanisms. Two essential elements of a biological oscillator are 1) an inhibitory feedback loop, which includes one or more oscillating variables, and 2) a source of delay in this feedback loop, which allows an oscillating variable to overshoot a steady-state value before the feedback inhibition is fully effective. The analysis of the patterns of interactions and delays observed in biological oscillators is simplified by the translation of variables, interactions, and delays into schematic representations. To illustrate how such translations can be implemented, three biological oscillators are described schematically: 1) the glycolytic oscillator, 2) the bursting of the molluscan neuron, R15, and 3) the oscillations underlying smooth muscle contractions.
Preferential utilization of brown adipose tissue lipids during arousal from hibernation in hamsters
Authors: Nedergaard J. , Cannon B.
Published: December 2017

The participation of brown adipose tissue in the arousal process of golden hamsters was studied. The utilization of lipids in different depots of brown adipose tissue was followed gravimetrically. From both the interscapular and the cervical brown adipose tissue depots, 28 mg of lipid were lost during arousal; there was no measurable loss of lipid from the white adipose tissue depots. The total weight of eight identified depots of brown adipose tissue in nonhibernating, cold-acclimated hamsters was estimated to be 1,700 mg, of which 475 g were lipid. It is calculated that a total of 255 mg lipid disappeared from brown adipose tissue during arousal; this lipid is theoretically capable of giving rise to 2.4 kcal (9.9 kJ) of heat. It is concluded that the heat produced by the combustion of the lipid that disappeared from the brown adipose tissue during the arousal process could be the major source of the heat needed to rewarm the hamster from hibernating to euthermic body temperatures.