bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of 4-pentenoic acid on renal phosphate and calcium excretion in the dog
Authors: Yeoh HH , Rice LE , Maggio A , Levin ML
Published: December 2017

The effects of 4-pentenoic acid (4-PA) on renal excretion of phosphate and calcium were studied in anesthetized mongrel dogs. The major metabolic action of 4-PA is inhibition of long-chain fatty acid oxidation. In intact dogs undergoing modest saline diuresis, 4-PA caused significant decrease in the percentage of filtered phosphate reabsorbed. No statistically significant calciuria was observed. Similar results were observed in intact dogs undergoing more brisk saline diuresis as well as in acutely and chronically thyroparathyroidectomized dogs. However, when results were pooled, both phosphate and calcium excretions were significantly increased. The results are interpreted as demonstrating the importance of fatty acid oxidation in providing energy for the work of tubular phosphate reabsorption. Either the energy source for calcium reabsorption differs from fatty acid oxodation, or calcium reabsorption is less sensitive to changes in energy sources. The action of 4-PA is independent of the forces involved in saline diuresis and of parathyroid hormone.
Effect of colchicine on urinary phosphate and regulation by parathyroid hormone
Authors: Dousa TP , Duarte CG , Knox FG
Published: December 2017

The possible role of cytoplasmic microtubules in the renal handling of phosphate and its regulation by parathyroid hormone (PTH) was evaluated with colchicine, a microtubule-disrupting agent. Colchicine-treated rats were thyroparathyroidectomized (TPTX) and subsequently infused with PTH. Treatment with a total dose of 1 mg colchicine had no effect on glomerular filtration rate or fractional excretions of sodium and potassium. Fractional excretion of phosphate in colchicine-treated TPTX rats was significantly higher compared with TPTX controls. After PTH infusion, control rats responded with increases in fractional excretion of phosphate and urinary cyclic AMP but colchicine-treated rats had variable and insignificant changes in both parameters. Fractional excretion of sodium and potassium did not change significantly after PTH. Renal cortical activities of cyclic AMP phosphodiesterase, soluble alkaline phosphatase, cytochrome oxidase, leucine aminopeptidase, or basal adenylate cyclase were not significantly affected by colchicine treatment. On the other hand, stimulation of adenylate cyclase by a submaximal dose of PTH was markedly decreased in colchicine-treated rats, and the activity of membrane-bound alkaline phosphatase was also significantly decreased. The binding of radioactive colchicine in renal cortical extracts from rats treated with colchicine was significantly diminished. These results suggest that disruption of cytoplasmic microtubules in renal cortical cells interferes with phosphate transport and its regulation by PTH.
RENAL HANDLING OF CITRATE DURING HEAT-INDUCED HYPOCITRICEMIA
Authors: Gold AJ , Costello LC
Published: December 2017

A model of steady-state hypocitricemia, characterized by hypocitraturia and reduced kidney cortex citrate, has been demonstrated in the rate chronically exposed to environmental heat. The renal citrate extraction ratio remains unchanged. The physiological mechanism that brings about the reduction in circulating citrate has not been determined. Hypocitraturia likely results from a decreased filtered citrate load. Although it is generally contended that filtered citrate load. Although it is generally contended that alkalosis increases and acidosis decreases renal excretion of citrate, observations of mild alkalosis and hypocitraturia during heat exposure suggest that factors other than pH can alter renal handling of citrate. Kidney mitochondrial function, as determined by in vitro measurements of citrate-stimulated respiratory rates and specific activities of isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and cytochrome c oxidase, appears to be unaffected by environmental heat.
Left ventricular force-length relations of isovolumic and ejecting contractions
Authors: Weber KT , Janicki JS , Hefner LL
Published: December 2017

To determine the interrelationships between ejecting and isovolumic force-length relations and the extent to which the left ventricle will shorten, data obtained in 27 isolated, servo-regulated hearts were examined. For each heart a series of contractions, variably loaded (delta L) were derived for a thickwalled sphere and normalized by the cross-sectional area of muscle and length at zero end-diastolic pressure. It was found that within the physiological range examined total and active force were essentially a linear function of initial L with respective increments or reductions in slope produced by positive or negative shifts in contractile state. The force-L relations obtained isovolumically and at end ejection were virtually identical. For a given ejection pressure, end-systolic L was constant, despite variations in filling and therefore independent of initial L and deltaL; moreover, the L to which the ventricle shortened was determined by the course of the systolic force L-relation. Thus, irrespective of loading, delta L occurs within the confines of the contractile state-dependent isovolumic force-L relation and where the latter is equivalent to the end-systolic force-length relation.
Effects of food deprivation on protein synthesis and degradation in rat skeletal muscles
Authors: Li JB , Goldberg AL
Published: December 2017

The effects of food deprivation on protein turnover in rat soleus and extensor digitorum longus (EDL) were investigated. Muscles were removed from fed or fasted growing rats, and protein synthesis and breakdown were measured during incubation in vitro. Rates of synthesis and degradation were higher in the dark soleus than in the pale EDL. One day after food removal protein synthesis and RNA content in the EDL decreased. On the 2nd day of fasting, rates of protein catabolism in this muscle increased. Little or no change in synthesis and degradation occurred in the soleus. Consequently, during fasting the soleus lost much less weight than the EDL and other rat muscles. In unsupplemented buffer or in medium containing amino acids, glucose, and insulin, the muscles of fasted rats showed a lower rate of protein synthesis expressed per milligram of tissue but not per microgram of RNA. Thus the decrease in muscle RNA on fasting was responsible for the reduced synthesis observed under controlled in vitro conditions. In vivo the reduction in muscle protein synthesis on fasting results both from a lower RNA content and lower rate of synthesis per microgram of RNA. Reduced supply of glucose, insulin, and amino acids may account for the lower rate of synthesis per microgram of RNA demonstrable in vivo.
Integration of the cardiovagal mechanism in the medulla oblongata of the cat
Authors: Chen HI , Chai CY
Published: December 2017

The central cardiovagal mechanism of the medulla oblongata was explored by stimulation and ablation techniques in the anesthetized cat. Insertion of an electrode into the nucleus solitarius (NS) occassionally evoked slight and transient bradycardia, but similar mechanical irritation to the nucleus ambiguus (NA) usually evoked prolonged and intense bradycardia. Electrical stimulation of the dorsal motor nucleus of the vagus (DNV) produced no or little bradycardia. Stimulation of NS and NA consistently produced cardiac slowing with a latency of less than 2 s and the effect was more prominent in the NA. Contralateral vagotomy did not significantly affect the bradycardia on the NS and NA stimulation but ipsilateral vagotomy caused a complete abolition. Lesions of the NA or DNV largely or completely abolished the bradycardia consequent to NS stimulation. Extensive destruction of the NS and/or DNV did not affect the bradycardia resulting from NA stimulation. Destruction of the ventral midline area partially reduced th bradycardia on NS STIMULATION BY 36-54%. The results suggest that the sequence of the three vagal nuclei for cardiac inhibition runs in the following order: NS, DNV, and NA. Synaptic connections are probably scanty in the DNV. Part of the vagal pathway passes through the ventral midline area before it reaches the NA. A scheme of the neural pathway for reflex bradycardia of vagal origin has been proposed.
Micropuncture studies of glucose transport in the dog: mechanism of renal glycosuria
Authors: Wen SF
Published: December 2017

Clearance and micropuncture studies were performed in 23 dogs without glucose loading to examine the tubule mechanism of renal glycosuria. Studies were carried out in three groups of animals before and after 10% extracellular volume expansion, and administration of maleic acid in low dose at 150 mumol/kg and in high dose at 300 mumol/kg. Specific hexokinase methods were used for the determination of glucose in tubule fluid and urine. Under control conditios, glucose reabsorption occurred predominantly in the proximal tubule. In all three groups, proximal tubule reabsorption of both sodium and glucose was inhibited in the second phase, showing a good correlation between the two. In contrast, fractional urinary glucose excretion remained unchanged after volume expansion and low-dose maleic acid, indicating reabsorption of virtually all the increased glucose load at a further "distal" site. On the other hand, significant glycosuria developed after high-dose maleic acid that was a result of reduced glucose reabsorption in the distal nephron, in addition to the proximal effect. It was concluded that distal glucose transport plays a significant role in regulating urinary glucose excretion and maintains renal thershold for glucose,
Frank-Starling relationship as an important determinant of fetal cardiac output
Authors: Kirkpatrick SE , Pitlick PT , Naliboff J , Friedman WF
Published: December 2017

The importance of the Frank-Starling mechanism was evaluated in seven chronically instrumented fetal lambs (128-141 days gestation). Continuous determinations of left ventricular (LV) internal dimensions and pressures were obtained while LV end-diastolic diameter (LVEDD) was reduced by superior vena cava occlusion and increased by infusion of fetal blood into left atrium. A highly significant relationship was found to exist between stroke volume and LV extent of shortening (delta D) (r = + 0.99, P less than 0.001). Altering LVEDD from 10,5 to 13mm or LV end-diastolic pressure from 2.5 to 8 mmHg resulted in a 68% augmentation, in delta D. Spontaneous respiratory efforts resulted in frequent beat-to-beat variations in LVEDD and delta D, which maintained cardiac output constant over a wide range of respiratory rates. Moreover, LV output determined by indicator-dilution techniques remained unchanged over a wide range of spontaneous heart rates (114-180 beats/min) as a result of changes in delta D appropriate to alterations in LVEDD. Thus, changes in resting myocardial fiber length are of fundamental importance in fetal cardiovascular homeostasis and, within physiologic limits, it is quite clear that the Frank-Starling mechanism is operative and effective in the fetal lamb;
Ion transport and structure of urinary bladder epithelium of Amphiuma
Authors: Mullen TL , Kashgarian M , Biemesderfer D , Giebisch GH , Biber TU
Published: December 2017

The urinary bladder of Amphiuma exhibits stable transport properties and an electrical potential difference in vitro. The lumen is significantly negative to the serosa and under short-circuited conditions flux rations for Na and Cl of 5.92 +/- 0.42 and 1.81 +/- 0.20, respectively, were observed. The close agreement between the short-circuit current and net Na flux suggests that most, if not all, of the current is carried by Na. Both ouabain and amiloride decreased the short-circuit current and the mucosal-to-serosal (M leads to S) flux of Na. Furosemide caused a transient increase in the M leads to S flux of Na and Cl but ADH was without effect. In bladders that had high transmural resistance, a net movement of K in the M leads to S direction under short-circuited conditions with flux ratios of up to 2 could be observed. The epithelium of the Amphiuma bladder consists of three cell types: granular cells, basal cells, and mitochondria-rich cells. No goblet cells are present. The mitochondria-rich cells comprise less than 5% of the population of the surface epithelium in Amphiuma in contrast to other amphibian bladders, where it accounts for up to 25% of the population.
Urate reabsorption in proximal convoluted tubule of the rat kidney
Authors: Weinman EJ , Steplock D , Suki WN , Eknoyan G
Published: December 2017

Urate reabsorption was examined in the rat utilizing clearance and in vivo microperfusion techniques. In control rats, the fractional excretion of urate averaged 12.5 +/- 1.3% of the filtered load, with 60-70% of perfused urate reabsorbed at 2 mm of perfused tubule length (urate efflux). Increasing the perfusion concentration of urate to 6, 12, and 25 mg/100 ml did not alter the fractional rate of reabsorption. The acute administration of chlorothiazide resulted in a fall in GFR and Curate such that the fractional excretion was unchanged from controls and averaged 13.3 +/- 2.0%, without an associated change in urate reabsorption from proximal perfusates despite the presence of significant inhibition of sodium and water reabsorption. By contrast, the chronic administration of chlorothiazide accompanied by a low-sodium diet resulted in a significantly lower fractions excretion rate of urate of 7.95 +/- 0.5% and a significant increase in reabsorption of sodium and water as well as urate from microperfusates, In control rats receiving an infusion of 5% mannitol in isotonic saline, urate secretion was demonstrated by the urinary precession of [2-14C]urate from [methoxy-3H]inulin following placement of these isotopes on the surface of the kidney. The additional infusion of chlorothiazide did not alter this pattern of isotope recovery in the urine.
Effect of the histamine (H2) inhibitor metiamide on histamine-stimulated bile flow in dogs
Authors: Kaminski DL , Ruwart MJ , Jellinek M
Published: December 2017

The effects of the histamine H2-receptor inhibitor metiamide on histamine-stimulated canine bile flow and gastric hydrogen ion output were evaluated. Histamine was found to stimulate bile volume in doses comparable to those that stimulated gastric hydrogen ion output; both responses appeared to have the same maximal response dose, 150 mug/kg per h. Metiamide alone did not alter hepatic bile flow. Administration of metiamide, 2 mg/kg per h, along with various doses of histamine demonstrated that the H2-receptor antagonist decreased bile volume and gastric hydrogen ion output from values obtained with histamine administration alone. The D50 of histamine for bile flow was 16.3 mug/kg per h and the D50 for hydrogen ion output was 44.2 mug/kg per h, Kinetic analysis suggests that the decrease in histamine-stimulated hydrogen ion output produced by metiamide is the result of competitive inhibition; the decrease in histamine-stimulated bile volume by metiamide which is different from the hydrogen ion inhibition, suggests noncompetitive inhibition. These data indicate that the mechanism of histamine choleresis is different from the mechanism of histamine-stimulated gastric acid output and that histamine-stimulated bile flow may not be the result of direct hormone-receptor interaction.
Renal sugar transport in the winter flounder. I. Renal clearance studies
Authors: Pritchard JB , Kleinzeller A
Published: December 2017

The renal handling of several sugars was examined using clearance techniques in the winter flounder Pseudopleuronectes americanus. The nonmetabolizable sugar alpha-methyl-D-glucoside was extensively reabsorbed, with consequent accumulation in renal tissue to nearly twice plasma concentration. Both glucose and phlorizin abolished reabsorption and reduced tissue-to-plasma ratios (T/P). D-Galactose was reabsorbed. However, the T/P for free galactose was only 0.6 (total sugar was 1.7). Glucose and phlorizin produced only a transient decrease in reabsorption and no change in T/P. 2-Deoxy-D-glucose showed neither net reabsorption nore secretion. Nevertheless, kidney T/P were inexcess of 6 for total sugar and 1.2 for free sugar, indicating entry through the peritubular face of the tubule. Neither glucose nor phlorizin altered 2-deoxy-D-glucose clearance, but both reduced T/P for total sugar (2.4) and free sugar (0.7). Thus, several systems govern the handling of these sugars at the luminal membrane of the renal tubule, just as has been previously demonstrated at the peritubular membrane in this species.
Organic solutes in fluid absorption by renal proximal convoluted tubules
Authors: Burg M , Patlak C , Green N , Villey D
Published: December 2017

Proximal convoluted tubules were dissected from rabbit kidneys and perfused with artificial solutions in vitro. The effect of various organic solutes on rate of fluid absorption and transepithelial voltage was tested by removing solutes from or adding them to perfusate and/or bath. Omission of albumin from the bath caused rate of fluid absorption to descrease 33% without any change in voltage. Omission of glucose, lactate, alanine, and citrate from the bath had no effect. In contrast, when they were removed from perfusate, rate of fluid absorption fell by 45-75% (depending on whether they were replaced by NaCl or mannitol and NaCl), and voltage (normally negative in lymen) decreased to near zero. Adding glucose or alanine individually to perfusate caused a small increase in rate of fluid absorption and a relatively large increase in voltage. alpha-Methyl-D-glucoside and cycloleucine (which are transported but not metabolized) had effects similar to glucose and alanine, except that voltage changes were not as great. Phlorizin (10(-5) M in perfusate) had the same effect as removing glucose from perfusate. When glucose and alanine were added to perfusate, epithelial cell swelled significantly. Lactate and citrate also caused rate of fluid absorption to increase when they were added to perfusate, but they did not affect transepithelial voltage nor did they cause cells to swell significantly. Possible mechanisms of these effects and the role of organic solutes in fluid absorption by proximal convoluted tubules are discussed.
Metering of intravenous versus oral nutrients and regulation of energy balance
Authors: Nicolaidis S , Rowland N
Published: December 2017

Unrestrained rats received continuous and discontinuous intravenous infusions of nutritive substances over long periods, and the effects on energy regulation were examined. Oral food intake was decreased by all glucidic infusions, but by less than the theoretical (caloric) value of the infused substances. A residual oral food intake thus persisted when the energy needs were supplied intravenously, and rats with the greater residual intakes gained excessive body weight. The less nutritionally balanced the infusion, the less the reduction in food intake, which suggests that some of the residual oral feeding may be due to a specific appetite for missing elements. The reduction of oral intake became equal to the calories infused when exogenous insulin was coinfused, and results from discontinuous infusions showed a similar trend. A model for the metering of nutrients at the systemic level was proposed; only when substances are metabolized is there a direct effect on feeding control mechanisms.
Canine pancreatic response to intestinally perfused oligopeptides
Authors: Meyer JH , Kelly GA , Jones RS
Published: December 2017

Although older work indicated that luminal peptides are stimulants of pancreatic secretion, these earlier experiments were performed with crude peptide mixtures containing amino acids that are also known stimulants. Furthermore, no information was provided about size or composition of stimulating peptides. For this reason, the problem was reinvestigated with commercially synthesized oligopeptides in dogs equipped with chronic gastric and pancreatic fistulas. Synthetic peptides at 30 mM concentrations were perfused into the proximal bowel when luminal pancreatic proteases were reduced to undetectable concentrations and dogs were receiving intravenous exogenous secretin infusions. Increases in pancreatic outputs of protein and bicarbonate were measured. Of the peptides tested, only glycylphenylalanine, glycyltryptophan, and phenylalanylglycine stimulated, whereas both di- and triglycine were without effect. It was concluded that some, but not all, oligopeptides in the gut lumen are stimulants of pancreatic secretion.
Canine pancreatic responses to intestinally perfused proteins and protein digests
Authors: Meyer JH , Kelly GA
Published: December 2017

Pancreatic bicarbonate and protein secretory responses to intestinally perfused proteins or digests of proteins were measured in dogs with chronic gastric and pancreatic fistulas when luminalpancreatic protease concentrations were reduced to undetectable levels. Protein digests were analyzed for amino acid content, and various other indirect met-ods were used to assess the composition of the digest mixtures. Of five undigested proteins, none evoked more pancreatic secretion than a control perfusion with saline. Peptic digestion of these same proteins converted four of them to polypeptides that were poten stimuli of a pancreatic juice similar in HCO3-/protein ratios to that evoked by luminal amino acids. Dialyzed peptic digests of one of the proteins, bovine serum albumin (BSA), retained potency. Likewise, digestion of BSA with endogenous or exogenous pancreatic proteases converted the protein to a stimulus about equipotent with the peptic digest, though the composition of the pancreatic digests differed markedly from that of the peptic digests. We conclude that a) luminal peptides of four or more amino acids can stimulate the pancreas and b) during protein alimentation a wide array of luminal protein products may evoke pancreatic secretion.
Effect of prostaglandin E2 on ovine maternal placental blood flow
Authors: Rankin JH , Phernetton TM
Published: December 2017

The effect of PGE2 on regional blood flows in the chronically catheterized near-term pregnant sheep was investigated using radioactive microspheres. The injection of 20 mug PGE2 per kilogram into the left ventricle of eight sheep resulted in no change in maternal brain and noncotyledonary uterine flow. The renal blood flow increased from 692 to 892 ml/min (P less than 0.004). The uterine blood flow decreased from 673 to 317 ml/min (P less than 0.001). The trium was bypassed by injecting 7 mug PGE2 per kilogram of sheep into a fetal venous catheter and permitting it to reach the placental vasculature after placental transfer. Eleven sets of observations were made in eight animals. We observed no change in the intrauterine pressure, maternal brain flow, and noncotyledonary uterine blood flow secondary to this procedure. The maternal renal blood flow changed from 592 to 669 ml/min (P less than 0.007). The uterine blood flow increased from 762 to 853 ml/min (P less than 0.02). The uterine vascular resistance decreased from 0.124 to 0.115 mmHg x min/ml (P less than 0.04). It was concluded that 1) PGE3 crosses the placenta quite readily, and 2) PGE3 causes dilatation of the maternal placental vascular bed.
Sex and estrogens in protection against circulatory stress reactions
Authors: Altura BM
Published: December 2017

From Wistar rats, data are presented which indicate that inbred females a) have a greater ability to clear particulate matter from the blood stream than do males of the same strain; b) are significantly more resistant to two different forms of lethal circulatory stress (e.g., intestinal ischemia and whole-body trauma) than are males; and c) exhibit a greater resistance to undergo reticuloendothelial system (RES) phagocytic depression after both forms of lethal trauma than do males. Estradiol treatment of males, using either acute, massive (1 or 10 mg/kg) or multiple, low dose (10 or 100 mug/kg) regimens, confers trauma resistance on such animals. Such estradiol treated male rats exhibit hyperactive RES's. These estradiol-treated males, when subjected to either lethal ischemia or trauma, fail to demonstrate the early RES phagocytic depression seen in untreated controls. Untreated female as well as estradiol-treated male rats exhibit significantly higher arterial blood pressures post-trauma than do untreated male rats. Direct microscopic observation of rat mesenteries indicr whole-b0dy trauma, the untreated females as well as the estradiol-treated males exhibit significantly less dilatation of microscopic capacitance vessels (i.e., venules) than do untreated male rats. The data reported herein could be used to suggest that estrogenic hormones may play pivotal roles in a) the amelioration of an organism's reaction to systemic stress; and b) control of macrophage and peripheral vascular functions.
Effect of fatty acids on renal ammoniagenesis in in vivo and in vitro studies
Authors: Vinay P , Lemieux G , Cartier P , Ahmad M
Published: December 2017

Intravenous or renal intra-arterial infusion of sodium octanoate results in a 60% decrease in renal ammoniagenesis in the acidotic dog. Mobilization of endogenous fatty acids by levarterenol infusion is accompanied by a 30% fall in renal ammoniagenesis which coincides with considerable increase in renal extraction of fatty acids. In both types of experiments, the renal extraction of glutamine falls in proportion with decreased ammoniagenesis. The effect of octanoate and levarterenol infusion cannot be explained by changes in acid-base equilibrium, renal hemodynamics, or the release of insulin. In vitro experiments using kidney cortical slices from acidotic dogs show that addition of sodium octanoate (0.05-10 mM) or sodium palmitate (0.1-2.5 mM) to the incubation medium induces a 35% decrease in both ammonia and glucose production when L-glutamine (1 mM) is used as the basic ammoniagenic and gluconeogenic substrate. Glutamine uptake decreases concomitantly, whereas tissue glutamate either rises or remains unchanged. The same results were observed when L-glutamate (5 mM) was used as substrate. Glycerol (5 mM) in the medium has no effect on ammoniagenesis, whereas gluconeogenesis increases by 81%. The present studies demonstrate that fatty acids may interfere with renal ammoniagenesis from glutamine during acidosis. The effect is probably related to substrate availability and competition. Fatty acids appear to inhibit ammoniagenesis in the mitochondria through a direct metabolic effect linked with their oxidation and not through modification of glutamine transport across the mitochondrial membrane.
Thermoregulation in fasting emperor penguins under natural conditions
Authors: Le Maho Y , Delclitte P , Chatonnet J
Published: December 2017

Emperor penguins breed during the cold antarctic winter. The males incubate the single egg while fasting for up to 4 mo and losing some 20 kg of their body mass. Fasting captive birds under outdoor conditions lost from 0.145 to 0.434 kg day -1. Mean resting metabolic rate, 49.06 W for 24.8 kg body mass, is 7 and 27%, respectively, higher than predicted from general metabolic equations for birds. Minimal thermal conductance, 1.31 W m-2 degrees C-1, is within the range for other birds. The lower critical temperature is about -10 degrees C; this can be related to large body size (20-40 kg) and to body shape, giving a smaller relative surface area than for other birds. Rigidity of the feathers explains why winds of moderate speed (up to 5 m s-1) have little effect on heat loss. At very low temperatures the behavior of huddling close together is essential in reducing metabolic rate. Without this behavior, survival during the long fast (up to four mo) at winter temperatures would be impossible.
Effect of dorsal root section on the arrhythmias associated with coronary occlusion
Authors: Schwartz PJ , Foreman RD , Stone HL , Brown AM
Published: December 2017

In anesthetized vagotomized dogs and cats the circumflex and/or the anterior descending coronary artery were briefly occluded (5-90 s), and ectopic beats occurring during the occlusion and for 60 s following release were counted. When arrhythmias were regularly produced for a given occlusion, the dorsal roots from C8 to T5 were transected and the occlusions were repeated. Dorsal root section produced minor changes in heart rate and blood pressure. Dogs and cats did not differ in their responses. Dorsal root section was performed in eight animals and decreased the absolute number of ectopic beats by 63 +/- 19% compared to control values (P less than 0.05). In four animals the effect on ectopic beats produced by repeated occlusions without dorsal root section was investigated and found to be increased by 35 +/- 24% compared to contrl values. Most of the somatic afferents contained in the dorsal roots were damaged by the surgical preparation. Therefore, repeated occlusions and interruption of somatic afferents do not appear to have influenced our results. The arrhythmogenic interaction between the local effects of myocardial ischemia and the sympathetic activity, whose outlow contained in the ventral roots remained intact, was still possible after dorsal root section and this explains why ectopic beats were reduced but not almost suppressed as is usually the case after bilateral stellectomy. We conclude that dorsal root section reduces the number of ectopic beats associated with short-lasting coronary artery occlusions and that the most likely mechanism is the interruption of the cardiocardiac sympathetic reflex which depends upon afferent fibers running through the dorsal roots.
Uptake and release of hormones and metabolites by tissues of exercising leg in man
Authors: Rennie MJ , Park DM , Sulaiman WR
Published: December 2017

To examine release of insulin from tissues of the exercising llin, growth hormone, cortisol, and circulating metabolites were studied in five men before, during, and after exercise on a bicycle ergometer at 60% of their maximum work capacity. At rest, insulin, growth hormone, and cortisol were taken up by leg tissues. During exercise arterial plasma insulin concentration fell, but cortisol and growth hormone levels rose; there was net release of insulin into venous blood but little change in uptake of cortisol and growth hormone. Insulin release persisted after exercise for 15-30 min. During exercise arterial concentrations and uptake of glucose and free fatty acids (FFA) increased. Examination of the changes in hormones and metabolites failed to identify any single hormonal or metabolic factor causing the observed reversal of insulin uptake with exercise.
Alpha-adrenergic regulation of Na-Cl cotransport in human airway epithelium
Authors: Liedtke C. M.
Published: December 2017

The demonstration of abnormal beta-adrenergic and cAMP-modulated apical Cl- channels in cystic fibrosis (CF) airway epithelial cells suggests that other transporters, which are required for Cl- secretion, may also be abnormally regulated. A basolateral cotransporter was investigated by determining the initial rate of 36Cl efflux from cells isolated from CF nasal polyps or trachea and non-CF trachea. Cells were preequilibrated with radioactive tracer at 25 degrees C, and tracer transport was initiated by 10-fold dilution of an aliquot of cells in radioisotope-free medium. The initial rate of Cl transport was calculated from the linear portion of the efflux curves. In CF and non-CF cells, base-line Cl- transport was not blocked by furosemide but was stimulated twofold by l-epinephrine in Ca2+-deficient and Ca2+-replete transport medium. In both types of cells, furosemide blocked 70 and 77%, respectively, of the stimulated Cl- transport. Prazosin, an alpha 1-adrenergic antagonist, blocked the effects of l-epinephrine and methoxamine, an alpha 1-adrenergic agonist, stimulated prazosin- and furosemide-sensitive Cl transport. Ionomycin mimicked the effects of l-epinephrine. l-Isoproterenol, a beta-adrenergic agonist, did not affect Cl transport. The results of this study indicate an alpha 1-adrenergic stimulation of furosemide-sensitive Cl transport in human airway epithelium that functions normally in CF airway epithelial cells. The transport mechanism is probably a Na-Cl or Na-K-2Cl cotransport located in the basolateral membrane and requires elevated intracellular Ca2+ for activation.
Roles of mast cell tryptase and chymase in airway function
Authors: Caughey G. H.
Published: December 2017

Mast cells are abundant and are widely distributed in airway tissues. They release their secretory products into microenvironments as diverse as epithelium, smooth muscle, and glands. The major secretory granule proteins of mast cells are proteases that are released outside of the cell with heparin, histamine, and other preformed mediators. In the past few years, investigations in a number of laboratories have rapidly increased our knowledge of the chemical and biological properties of the two major mast cell secretory proteases, tryptase and chymase. Recent experimental evidence suggests the possibility of biologically important roles for tryptase and chymase in the airways, particularly in the regulation of neuropeptide activity, bronchomotor tone, and submucosal gland secretion. The purpose of this commentary is to examine critically the evidence of participation of these mast cell proteases in molecular and physiological events in the airways.
Role of physical forces in compensatory growth of the lung
Authors: Rannels D. E.
Published: December 2017

In many species, partial resection of the lung leads to rapid compensatory growth of the remaining tissue to restore normal lung mass and function. The response to partial pneumonectomy is closely controlled; both its rate and nature are subject to hormonal modulation. Physical factors, particularly distortion of the lung by altered inflation, are likely involved in regulation of the response, although the details of the regulatory mechanisms are not understood. In a number of tissues including the lung, application of external physical force leads to both acute and long-term changes in metabolism. In some cases these include cell growth and division, along with increased production of extracellular matrix components. Similar responses have been described after application of stress to isolated cells in culture. Independent lines of investigation have defined dramatic influences of cell shape on growth, differentiation, and metabolism, but stress-strain relationships at the cellular or subcellular levels are poorly defined. The mechanisms by which changes in cell shape are transduced to intracellular signals likely depend on receptor-mediated interactions with the cytoskeleton, but strain-associated transduction pathways may involve stretch-sensitive ion channels, G protein-dependent reactions, the action of locally produced autocrine or paracrine factors, or a combination of these factors. These observations suggest a general model of the response to pneumonectomy that may be used to formulate specific hypotheses as a basis for future investigations. This approach will provide insight into the mechanisms by which physical forces influence growth and metabolism in the lung and other tissues.
Mechanism of phorbol ester inhibition of histamine-induced IP3 formation in cultured airway smooth muscle
Authors: Murray R. K. , Bennett C. F. , Fluharty S. J. , Kotlikoff M. I.
Published: December 2017

Cytosolic calcium is a key determinant of the contractile state of airway smooth muscle (ASM). To investigate the mechanisms by which histamine affects cytosolic calcium, we measured changes in inositol 1,4,5-trisphosphate (IP3) following the addition of histamine to cultured canine ASM cells. The effect of phorbol 12-myristate 13-acetate (PMA) on IP3 formation was investigated under conditions previously shown to abolish histamine-induced calcium release. In both intact cells and ASM membranes, histamine produced a significant increase in IP3 formation, which was inhibited by PMA. The site of this blockade was investigated by examining the effect of PMA on guanine nucleotide-stimulated IP3 formation and on phosphoinositide-specific phospholipase C (PI-PLC) activity in ASM membranes. Guanine nucleotide-stimulated IP3 formation was inhibited by PMA pretreatment. Membrane-associated PI-PLC activity was also decreased, an effect that was not due simply to a shift in the calcium sensitivity of the enzyme. We conclude that in cultured canine ASM cells, PMA blocks histamine-induced IP3 formation and that this inhibition is caused, in part, by a postreceptor site of action of protein kinase C, possibly via a direct effect on PI-PLC.
New "rest period" protocol for inducing tolerance to high O2 exposure in adult rats
Authors: Frank L. , Iqbal J. , Hass M. , Massaro D.
Published: December 2017

We report a new protocol for inducing marked tolerance to prolonged exposure to hyperoxia in adult rats that entails the use of a single "rest period" between exposures to a usually lethal concentration of O2. Exposure of adult rats to greater than 95% O2 for 48 h followed by a rest in air, or a rest even in 50-75% O2, consistently resulted in 100% survival with evidence of only slight pulmonary edema during continuation of exposure to greater than 95% O2 for 3-7 more days (7-day survival for rats rested in room air for 24 h = 23/23; for rats rested in 50-75% O2 for 24 h = 27/27; for continuously O2-exposed control rats = 0/11). Induction of tolerance to hyperoxia was associated with significant increases in the lungs' antioxidant enzyme activities during the reexposure to greater than 95% O2 following the rest period. The molecular means by which the events in this protocol lead to increased lung antioxidant enzyme activity is only partially known, but because of the marked tolerance produced, the elucidation of the mechanisms must be important to our understanding of tolerance to hyperoxia.
Tumor necrosis factor and interleukin 1 alpha increase vascular endothelial permeability
Authors: Royall J. A. , Berkow R. L. , Beckman J. S. , Cunningham M. K. , Matalon S. , Freeman B. A.
Published: December 2017

Endotoxic shock is associated with acute vascular endothelial injury resulting in edema. Tumor necrosis factor (TNF) and interleukin 1 (IL-1) are cytokines produced by endotoxin-stimulated mononuclear phagocytes that are potential mediators of endotoxic shock. In this study, we investigated the effects of TNF and IL-1 alpha on vascular endothelial cell permeability in vitro. The movement of radiolabeled macromolecules of different sizes (57Co-vitamin B12, 125I-cytochrome c, and 131I-albumin; 6.5-35A) across bovine aortic endothelial cell monolayers was measured after exposure to these cytokines. TNF induced a time- and dose-dependent increase in endothelial cell monolayer permeability that was enhanced in the presence of serum. The peak increase was noted after 12 h of incubation with less alteration of permeability with longer incubations. IL-1 alpha caused a similar time-dependent increase in endothelial cell monolayer permeability, but the peak effect of IL-1 alpha was seen after 24 h. Therefore the increased permeability seen with TNF cannot be explained by release of endogenous IL-1 alone. Neither TNF nor IL-1 alpha increased release of [14C]adenine, and the only effect on lactate dehydrogenase release was a small, but statistically significant, increase after 24 h of incubation. From these studies, we conclude that TNF and IL-1 alpha directly increase vascular endothelial cell permeability in vitro and speculate that these cytokines may be involved in the acute vascular endothelial injury associated with endotoxic shock.
Evidence for active H+ secretion by rat alveolar epithelial cells
Authors: Lubman R. L. , Danto S. I. , Crandall E. D.
Published: December 2017

A plasma membrane proton-translocating adenosinetriphosphatase (ATPase) has been identified in rat alveolar pneumocytes in primary culture using the pH-sensitive fluorescent probe 2',7'-biscarboxyethyl-5,6-carboxyfluorescein. Intracellular pH (pHi) was acutely lowered by NH3 prepulse in HCO3(-)-free medium buffered with 6 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, and its recovery was measured thereafter under control conditions, in the presence of amiloride to inhibit Na(+)-H+ antiport, and in the presence of N-ethylmaleimide (NEM), a plasma membrane H(+)-ATPase inhibitor. Initial rate of pHi recovery was reduced by 67% in the presence of amiloride, 52% in the presence of NEM, and 96% in the presence of both. Recovery was decreased but not abolished in Na(+)-free buffer, was essentially abolished when NEM was present in the absence of Na+, and was also abolished by addition of the metabolic inhibitor KCN in glucose- and Na(+)-free medium. These data suggest that alveolar epithelial cells possess a plasma membrane H(+)-ATPase. In Na(+)-containing buffer at pH 7.4, steady-state pHi was 7.50. This value was unaffected by amiloride but decreased to 7.01 in the presence of NEM, suggesting active H(+)-ATPase and inactive Na(+)-H+ antiport at steady-state pHi. We conclude that this plasma membrane proton-translocating ATPase in alveolar pneumocytes may be an important mechanism contributing to regulation of steady-state pHi, recovery from acute intracellular acidification, and modulation of extracellular alveolar fluid pH.
The cell biology and pathogenic role of pulmonary intravascular macrophages
Authors: Warner A. E. , Brain J. D.
Published: December 2017

Pulmonary intravascular macrophages (PIMs) are an extensive population of mature phagocytic cells adherent to the pulmonary capillary endothelium in selected species. They are not prevalent in lungs of commonly studied laboratory animals, such as rodents, and thus have only been recently appreciated. However, their potential role in host defense and acute lung injury has attracted interest, since a number of studies have demonstrated pulmonary localization of circulating particles, microbes, and endotoxin by PIMs. Those animal species, such as ruminants, that provide useful models of pathogen (or endotoxin)-induced acute lung injury demonstrate rapid pulmonary uptake of bacteria by PIMs. Inflammatory mediators released by activated PIMs may initiate the process and provoke accumulation of neutrophils and platelets. This review summarizes the morphological characteristics of PIMs and their species distribution. The role of these members of the mononuclear phagocyte system, both beneficial and potentially pathogenic, is reviewed. The question of whether PIMs have a role in acute lung injury in humans is also discussed.
Sodium efflux from isolated submucosal gland in feline trachea
Authors: Sasaki T. , Shimura S. , Ikeda K. , Sasaki H. , Takishima T.
Published: December 2017

We examined Na efflux, as an indicator of electrolyte (or water) secretion from isolated feline tracheal submucosal glands. After incubation with 22NaCl-containing KRB solution (pH 7.4) at 37 degrees C, the 22Na-loaded glands were transferred to a superfusion apparatus in which perfusate was continuously pumped to the glands at a flow rate of 2.5 ml/min and sampled at 18-s intervals for 10-15 min. After 5 min of perfusion, a pharmacological or electrical field stimulation (FS) was given to the isolated glands. The instantaneous rate constant was calculated by measuring the radioactivity (counts/min) of each effluent sample. The mean rate constant of the base-line 22Na efflux was 0.21 min-1, which fell significantly to 0.03 min-1 after treatment with ouabain. Both methacholine and phenylephrine significantly accelerated the 22Na efflux to 3.6-fold and 1.8 times base-line efflux, respectively. FS produced a significant increase in the rate constant, and the increase was abolished by pretreatment with ouabain or tetrodotoxin. Further, atropine or phentolamine significantly suppressed the FS-evoked increase in the rate constant to 76 and 84%, respectively, of the maximal response evoked by FS alone. These results indicate that Na efflux from feline tracheal submucosal glands, which is dependent on ouabain-sensitive Na-K-ATPase activity in the secretory cells, is stimulated by both cholinergic and alpha-adrenergic agonists.
Tumor necrosis factor-alpha augments pulmonary arterial transendothelial albumin flux in vitro
Authors: Goldblum S. E. , Sun W. L.
Published: December 2017

Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator of pulmonary vascular endothelial injury. We studied the effect of human recombinant TNF alpha (rTNF alpha) on transfer of 14C-labeled bovine serum albumin (BSA) across cultured bovine pulmonary arterial endothelial cell monolayers. rTNF alpha induced a dose-, time-, and temperature-dependent increment in transendothelial [14C]BSA flux. Only after an incubation time of greater than or equal to 4 h did rTNF alpha significantly (P less than 0.005) increase transendothelial albumin flux. rTNF alpha exposure times as brief as 5 min induced significantly (P less than 0.005) increased albumin transfer at 6 h. Although this initial rTNF alpha-endothelial interaction was not temperature dependent, the subsequent barrier dysfunction could only be generated at 37 degrees C. The rTNF alpha-induced changes could not be ascribed to endothelial cell cytotoxicity and was not blocked by protein synthesis inhibition. The effects of rTNF alpha on endothelial permeability were reversible and not specific for albumin transfer. Therefore, rTNF alpha may influence the movement of macromolecules across the pulmonary vascular endothelial barrier.
Effects of hypoxia on endothelium-dependent relaxation of rat pulmonary artery
Authors: Rodman D. M. , Yamaguchi T. , Hasunuma K. , O'Brien R. F. , McMurtry I. F.
Published: December 2017

We have previously reported that the isolated rat branch pulmonary artery (PA) contracts when made hypoxic and that the contraction is dependent in large part on the presence of a functioning endothelium. This study tested if the hypoxic contraction was caused by reduced endothelium-derived relaxing factor (EDRF) activity. To do so we tested if chemical inhibitors of EDRF mimicked the effect of hypoxia, if PA guanosine 3',5'-cyclic monophosphate (cGMP) fell during hypoxic contraction, and if stimulation of smooth muscle cGMP attenuated hypoxic contraction. We found that the EDRF inhibitors hemoglobin and methylene blue caused a concentration-dependent increase in PA force that equaled that produced by hypoxia. PA cGMP decreased in endothelium-intact rings from 105 +/- 14 pM/g (wet wt) during normoxia to 41 +/- 9 pM/g during hypoxia. In endothelium-denuded rings normoxic cGMP was reduced to 32 +/- 10 pM/g with no further decrease during hypoxia. The endothelium-independent stimulators of cGMP, nitric oxide, and 8-bromo-cGMP, reduced maximum hypoxic contraction by 80 +/- 11 and 93 +/- 3%, respectively, whereas the endothelium-dependent stimulator acetylcholine did not. PA adenosine 3',5'-cyclic monophosphate (cAMP) fell only slightly during hypoxia and cAMP inhibitors failed to mimic the hypoxic contraction. We conclude that the hypoxic contraction of isolated rat PA is caused largely by decreased EDRF activity.