bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of serotonin on brown adipose tissue and on its sympathetic neurons
Authors: Steiner G , Evans S
Published: December 2017

Previously we have shown that there are two types of sympathetic neurons in the rat interscapular brown fat-pad: long adrenergic neurons with cell bodies located in the paraspinal ganglia and short adrenergic neurons with cell bodies located within the pad itself. The present studies examine 1) the uptake of [3H]norepinephrine by these neurons, 2) the effect of serotonin on release of the catecholamine, and 3) the metabolic action of serotonin on brown fat. [3H]norepinephrine uptake from the medium in which brown fat slices are incubated is linear with time up to 90 min. This uptake is blocked by both cocaine and imipramine. As these drugs block uptake by sympathetic neurons, the [3H]norepinephrine is probably taken up by neurons and not by some other cell in the pad. Serotonin creatinine sulfate, but not creatinine sulfate, promotes the release of the catecholamine from these neurons. Serotonin also exerts a norepinephrine-like metabolic effect on slices of normal brown fat. It stimulates lipolysis and inhibits lipogenesis. Serotonin has no effect on isolated brown fat cells or on slices of reserpinized tissue. It also does not potentiate the action of norepinephrine on these last two preparations. Therefore serotonin's action on brown fat is mediated by norepinephrine-containing stromal cells. The data suggest that the rat brown fat-pad has sympathetic neurons that can take up norepinephrine and that serotonin exerts its metabolic effect by stimulating the release of norepinephrine from these neurons.
Effect of insulin on canalicular bile formation
Authors: Jones RS
Published: December 2017

Mongrel dogs were prepared by cholecystectomy, ligation of the lesser pancreatic duct, and insertion of gastric and duodenal cannulas. The common bile duct was cannulated through the duodenal fistula. After bile flow had been stabilized by intravenous infusion of sodium taurocholate the dogs were given an intravenous injection of insulin or 0.9% NaCl (control). Insulin caused marked increases in bile flow, chloride output, and biliary clearance of erythritol and small increases in bicarbonate output and bile salt output. The increased erythritol clearance indicates that canalicular secretion contributes to insulin choleresis in dogs.
Mineralocorticoid activity of 18-OH-DOC and DOCA in dogs with an aortic-caval fistula
Authors: Lohmeier TE , Davis JO , Freeman RH , Spielman WS , Watkins BE
Published: December 2017

The mineralocorticoid activity of 18-hydroxydeoxycorticosterone (18-OH-DOC) was measured during chronic electrolyte balance studies or during the postprandial increase in electrolyte excretion in conscious dogs with an aortic-caval fistula. In the chronic balance study, daily doses of DOCA and 18-OH-DOC ranging from 1 to 25 mg were administered intramuscularly for 3 consecutive days each, 6 h prior to feeding. For the postprandial study, 2-10 mg of DOCA and 18-OH-DOC were administered at feeding and postprandial electrolyte excretion was measured hourly for 6 h. Sodium and fluid retention in the dogs with an aortic-caval fistula was related to the dose of mineralocorticoid administered and equivalent sodium-retaining responses were achieved with 6-10 times more 18-OH-DOC than DOCA. Rapid absorption of both steroids was suggested from the postprandial measurements of urinary sodium excretion. Slight potassium retention occurred during the chronic administration of large doses of DOCA but the postprandial potassium responses produced by the steroids were variable and suggested a slight kaliuresis. The data also emphasize the importance of mineralocorticoids in sodium retention and ascites formation in this experimental model of high-output heart failure.
Mechanics and electrolyte composition of arterial smooth muscle in developing dogs
Authors: Cox RH , Jones AW , Swain ML
Published: December 2017

The effects of age on arterial smooth muscles (SM) mechanics and electrolyte composition were studied during growth and development in six litters of puppies and their mothers from isolated segments of carotid, renal, mesenteric, and iliac arteries. An increase in the maximum wall stress following both norepinephrine (NE) and potassium (K) was found with age at all sites. The ratio of the stress response for K/NE was found to decrease with age. The maximum stress response for both NE and K shifted to lower values of wall strain with age in the same manner that passive stress-strain curves were shifted. The maximum diameter re3 (3 SM activator to SM activator were not significantly altered with age, but they were better maintained at higher transmural pressure in older animals. Chemical analysis indicated "cell" water, Mg, and K contents decreased with age, as did extracellular water, Na, and Cl. Na anhe suggest that changes in SM excitation-contraction coupling occur with age. Passive wall elements appear to interact with the contractile elements in determining wall responses to SM activation.
Renal handling of [(14)C]mannose
Authors: McNamara PD , Rea C , Ozegovic B , Segal S
Published: December 2017

The uptake of D-[(14)C]mannose by adult rat kidney cortex slices has been examined. The process involved appeared to be saturable and oxygen dependent and to be inhibited by glucose, galactose, chi-methyl-D-glucoside, and phlorizin. Extensive metabolism of the sugar occurred. (14)CO(2) was produced to an extent comparable to that from D-glucose. Radioactive compounds accumulated in the tissue, approximately 50% of which were in the form of phosphorylated or other polar intermediates. The remaining neutral fraction consisted of mannose with a small amount of label in glucose and an unidentified compound which behaves like an alditol. Mannose concentration in the intracellular fluid was never greater than that of the medium.
Agonist and antimineralocorticoid activities of spirolactones
Authors: Sakauye C , Feldman D
Published: December 2017

To investigate the mechanism of action of antimineralocorticoids, a series of spirolactone analogues was evaluated for both mineralocorticoid antagonist and agonist activity. Antagonist activity was assessed by inhibition of aldosterone stimulated sodium transport employing toad bladder short-circuit current (SCC) measurements. Agonist activity was assessed in the same system by the direct effect of spirolactones on SCC. Opening of the gamma-lactone ring of a spirolactone dramatically decreased antagonist activity in the compound studied. Several C-7 chi-substitutions resulted in either enhanced or diminished activity, whereas deletion of the C-10 methyl group (i.e., 19-nor compound) had only minimal effects on antagonist potency. Agonist activity was demonstrable for three of the analogues studied: the 19-nor compound, and those containing a C-7 chi-substitution with a carboxyl isopropyl ester or a C-6-7 cyclopropyl linkage. The functional activity in toad bladder was compared to previous measurements of the relative binding affinity of the same spirolactones for mineralocorticoid receptors in rat kidney. Although there was some correlation between binding to rat kidney receptors and antagonist activity in the toad bladder, the results did not coincide in the case of the three spirolactones that possessed partial agonist activity. Some of the discrepancy may have resulted from differences between mammalian and amphibian receptors; however, intrinsic agonist activity limits antagonist potency and thus may cause a divergence between binding and functional studies limited to antagonist activity alone. Binding affinity, although indicative of total activity, fails to distinguish agonist from antagonist potency.
Hepatic venous compliance and role of liver as a blood reservoir
Authors: Lautt WW , Greenway CV
Published: December 2017

Changes in hepatic blood volume in response to rapid elevations in hepatic venous pressure were examined in cats using hepatic plethysmography. The liver was intact and received blood from an intact portal vein and hepatic artery. The hepatic blood volume increased in response to elevated venous pressure. Compliance of the hepatic capacitance vessels became greater as the distending venous pressure was increased over the range of venous pressures studied (0-9.4 mmHg). When hepatic venous pressure was elevated to 9.4 MMHg, the hepatic blood volume more than doubled. The liver serves as an important buffer for rapid changes in blood volume, the importance increasing with greater infused volumes of fluid. While overall venous compliance decreased at distending pressures in excess of 5-6 mmHg, the compliance of the hepatic capacitance vessels shows marked increases at pressures above this level. Expansions of the blood volume results in elevations of central venous pressure. Within a few minutes the hepatic capacitance vessels sequester a significant proportion of the added volume. As long as central venous pressure is raised, the liver demonstrates a secondary fluid buffering role by filtering large volumes of fluid across the vascular bed into the peritoneum.
Effect of norepinephrine and hypertonicity on K influx and cyclic AMP in duck erythrocytes
Authors: Kregenow FM , Robbie DE , Orloff J
Published: December 2017

Cyclic adenosine 3',5'-monophosphate (cAMP) accumulation and cation transport were measured in duck erythrocytes after stimulation by norepinephrine (NE) or shrinkage induced by exposure to hypertonic media (S). Previously both NE and S were shown to initiate a similar transport process in this cell. NE elicited a rapid rise in cellular cAMP and 42K influx. Both effects were eliminated by propranolol. At concentrations of NE below 3 X 10(-8) M (the concentration at which 42K influx saturates), there was good correlation between the magnitude of the permeability change and the increment in cAMP. In contrast, medium hypertonicity, at a level which stimulated K influx to the same extent as a near-maximal norepinephrine response, did not alter cAMP content. The data are discussed in terms of a model in which S and NE activate a final common transport pathway by different mechanisms, which in the case of S does not involve cAMP.
Role of sinoatrial ring bundle in internodal conduction
Authors: Hiraoka M , Sano T
Published: December 2017

The role of the sinoatrial ring bundle (SARB) in internodal conduction was examined by the microelectrode technique in excised rabbit hearts. The spread of the sinus impluse to the surrounding tissues was shown to proceed anteriorly toward the right branch of the crista terminalis significantly faster than toward the other direction. Thus the right SARB and the right branch of the crista terminalis close to the sinus node were the earliest areas excited by the sinus impulse in the areas surrounding the sinus node. It was further shown that the activation sequence does not initiate from the right SARB to the right branch of the crista terminalis via the junction of these two structures. Cutting the SARB did not produce any delay in conduction from the sinus node to the atrioventricular (AV) node. The conduction velocity measured at the endocardial surface by two microelectrodes has proved that conduction in the crista terminalis was significantly faster than in the SARB. The upstroke of the action potential from the crista terminalis was also steeper than that from the SARB. These results suggest that the SARB is not the main route for impulse propagation from the sinus node to the AV node; the fastest internodal conduction therefore takes place with wide wave fronts, along the crista terminalis.
Time course of ureteral changes with obstruction
Authors: Biancani P , Zabinski MP , Weiss RM
Published: December 2017

Chronic obstruction is characterized by a marked degree of ureteral dilatation and tortuosity which develops in the presence of a relatively low intraluminal pressure. To define the mechanism for the development of this relationship, the pressure-tension-deformation relationships of acute and chronically obstructed ureters were investigated. Rabbit ureters, in vivo, were obstructed and deformation correlated with intraluminal pressure. During the initial 3 h of obstruction, ureteral resting pressure increased from approximately 0 to 42 cm H2O, and diameter increased 16% with a slight increase in length. Subsequently, average wall tension (tensile stress) and intraluminal pressure declined, although deformation persisted. Between 6 h and 8 days after the onset of obstruction, intraluminal pressure remained essentially unchanged. During this time interval, ureteral deformation continued gradually and progressively as the ureter underwent creep both circumferentially and longitudinally. This was associated with a marked increase in average wall tension. At 8 days the diameter had increased by 170% and the length by 25%.
Compensatory adrenal growth: a neurally mediated reflex
Authors: Dallman MF , Engeland WC , Shinsako J
Published: December 2017

The responses of young rats to left adrenalectomy or left adrenal manipulation were compared to surgical sham adrenalectomy in which adrenals were observed but not touched. At 12 h right adrenal wet weight, dry weight, DNA, RNA, and protein content were increased (P less than 0.05) after the first two operations. Left adrenal manipulation resulted in increased right adrenal weight at 12 h but no change in left adrenal weight. Sequential manipulation of the left adrenal at time 0 and the right adreanl at 12 h resulted in an enlarged right adrenal at 12h (P less than 0.01), and an enlarged left adrenal at 24 h (P less than 0.05), showing that the manipulated gland was capable of response. Bilateral adrenal manipulation of the adrenal glands resulted in bilateral enlargement at 12 h (P less than 0.01). Taken together with previous results, these findings strongly suggest that compensatory adrenal growth is a neurally mediated reflex.
Lactate and contractile force in frog muscle during development of fatigue and recovery
Authors: Fitts RH , Holloszy JO
Published: December 2017

The relationship between lactic acid concentration and twitch tension was reevaluated in electrically stimulated frog sartorius muscle. In muscles stimulated under anaerobic conditions at a rate of 30 stimuli/MIN CONTRACTILE FORCE DECREASED TO 36% OF THE INITIAL VALUE IN 15 MIN, Concomitantly lactate increased from 3.3 to 18.7 mumol/g of muscle. The correlaiton between the increase in lactate and the decrease in contractile force was significant (r = -0.99, P less than 0.000001). Recovery occurred in two phases. A rapid increase in contractile force, which represented 20% of the total recovery, took place during the first 15 s and occurred concomitantly with an increase in ATP from 3.9 to 4.6 mumol/g. Lactate concentration did not change significantly during this period. The second phase of recovery of contractile force was complete in 50 min. Lactate concentration and contractile force were significatly correlated during recovery (r = -0;92, P less than 0.00001). However, recovery of contractile force lagged behind the decrease in lactate; a given concentration of muscle lactate was associated with a higher contractile force early during development of fatigue than late during recovery.
Noncompensation of adipose mass in partially lipectomized mice and rats
Authors: Faust IM , Johnson PR , Hirsch J
Published: December 2017

The effects of surgical ablation of adipose tissue were studied in normal mice and rats. It was found that: 1) restortation of adipose tissue does not occur locally in epididymal fat pads of young rats. 2) Bilateral epididymal fat pad removal in mice disrupts the testes and causes the other fat depots to accumulate excess lipid, but these effects are not sustained; After a sufficient recovery period, testes appear normal and no excess lipid is found in the remaining depots; 3) Temporary enlargement of remaining depots is probably due specifically to epididymal pad removal. It does not occur in response to inguinal depot removal, nor in response to disruption of the testes alone; 4)The quantity of lipid stored by a rapidly growing mouse depends on the number of intact depots in the mouse. These results suggest that surgical removal of fat does not lead to compensatory growth of fat. Autoregulation of adipose tissue mass, if it occurs, most likely operates through detection of adipocyte size rather than adipocyte number or total fat mass.
Afterload-induced homeometric autoregulation in isolated cardiac muscle
Authors: Donald TC , Peterson DM , Walker AA , Hefner LL
Published: December 2017

Pressure-induced homeometric autoregulation (HAR) has been demonstrated by many investigators in the mammalian ventricle; In isolated cardiac muscle, however, several investigators have reported the opposite effect (anti-HAR); namely, that the first beat after a transition from isotonic to isometric contraction is the most forceful, with a decline over several beats to a steady state. In the present study we find that trabeculae from the canine right ventricle demonstrate either HAR or anti-HAR, depending on the rate of stimulation, the calcium level, and the temperature. Higher calcium, higher temperature, and lower rate of stimulation produce either less HAR or more anti-HAR. When only temperature and rate of stimulation are varied, in each muscle there is a unique rate for each temperature above which HAR occurs and below which anti-HAR occurs.
Sympathetic nervous system and renin release from submaxillary glands in vitro
Authors: Michelakis AM , Menzie JW , Yoshida H
Published: December 2017

We previously reported that alpha- but not beta-adrenergic agonists stimulate renin release from mouse submaxillary glands in vivo. The present studies were undertaken to determine if these in vivo effects were due to a direct action on the submaxillary glands and to find out if cyclic AMP (cAMP) might be involved in submaxillary renin release. Pooled mouse submaxillary gland slices were incubated in Krebs-Ringer bicarbonate medium following a preincubation period, and renin release was measured by a radioimmunoassay for the direct measurement of submaxillary gland renin. Tissue cAMP levels were also measured. Addition of the alpha-adrenergic agonists, phenylephrine or norepinephrine, significantly increased renin release (P less than 0.01 vs. control) while decreasing tissue cAMP levels (P less than 0.01 vs. control). In contrast, addition of the beta-adrenergic agonist isoproterenol markedly increased cAMP levels (P less than 0.01 vs. control) and decreased renin release (P less than 0.05 vs. control). Pretreatment of the slices with the alpha-blocker phenoxy genzamine inhibited the effect of phenylephrine. These results indicate that alpha-adrenergic agonists cause renin release from submaxillary glands which is accompanied by a fall in tissue cAMP levels. This is in contrast to renin release from the kidney which is stimulated by beta-adrenergic agonists.
Effect of muscle length on 45Ca efflux in resting and contracting skeletal muscle
Authors: Frank JS , Winegrad S
Published: December 2017

The increment of the slow component of 45Ca efflux from frog skeletal muscle that is produced by electrical stimulation is reduced by 70% when the muscle has been stretched to 160% of in vivo length. No change in the efflux from resting muscles or the increment in influx associated with stimulation was produced by increased length. The increased efflux produced by 8 mM caffeine was not altered by increased muscle length. Resting and action potentials were unchanged by the stretching. No morphological changes were seen in the transverse tubules or their junction with the terminal cisternae even at sarcomere lengths of 3.8 muM, but the terminal cisternae themselves were elongated at this length.
Polyamine synthesis in liver and kidney of flounder in response to methylmercury
Authors: Manen CA , Schmidt-Nielsen B , Russell DH
Published: December 2017

The effect of methylmercury administration on polyamine synthesis was studied in the liver and kidney of the winter flounder (Pseudopleuronectes americanus). A single injection of methylmercury resulted in five- and sevenfold elevations of ornithine decarboxylase activity in the liver and kidney within 15 and 45 h, respectively. There were elevations of both putrescine- and spermidine-stimulated S-adenosylmethionine decarboxylase activities (approximately 1.5-fold) in both tissues. Evaluation of the polyamine accumulation patterns in these tissues indicated that in the liver all three polyamines increased in concentration until 48 h and then decline. In the kidney, the concentration of putrescine increased steadily until it was 200% of control at 72 h and then declined. Spermidine concentration decreased throughout the time studied and was 17% of control at 1 wk. There was no significant change in the concentration of spermine throughout the period studied. The changes in the polyamine pools and in the activities of the polyamine biosynthetic enzymes after methylmercury administration are consistent with an involvement of the polyamines in the recovery phase to a toxic dose of methylmercury.
H+ current response to CO2 and carbonic anhydrase inhibition in turtle bladder
Authors: Schwartz JH
Published: December 2017

To evaluate the role of CO2 and carbonic anhydrase (CA) in H+ transport (JH) by turtle urinary bladder the effect of CO2 addition, with and without addition of CA inhibitiors, was examined on JH. Since in the presence of exogenous CO2 and HCO3- the pH stat-measured rate of mucosal (M) acidification underestimates JH by the rate of electroneutral HCO3- secretion, the reverse short-circuit current (RSCC) applied across ouabain-treated bladders was used to estimate JH. That the RSCC is a measure of JH was demonstrated by: 1) in the absence of added CO2 and HCO3- the rate of M acidification totally accounted for the RSCC, and 2) increases in RSCC with CO2 addition occurred without changes in Na+ and K+ fluxes or the coupled ration of HCO3- secretion for Cl-absorption. When serosal (S) percent CO2 was progressively progressively increased JH achieved a maximum rate of 64 +/- 3 muA (SE) with 4.5% CO2. At higher S percent CO2 JH did not change, suggesting that factors other than the rate of CO2 hydration were rate limiting. The maximum rate of JH was not decreased by low concentrations of CA inhibitors (acetazolamide, 5 X 10(-5) M), although the percent CO2 at which this maximum rate occurred increased to 8.5%. The increased percent CO2 requirement for the maximum rate of JH with low concentrations of CA inhibitors suggests that these agents alter JH by decreasing the rate of enzymatic CO2 hydration. At high concentrations (acetazolamide, 5 X 10(-4) M) these inhibitors decrease the maximum rate of JH in the presence of CO2, implying that these inhibitors at higher concentrations directly interfere with the H+ transport system.
Alanine metabolism and gluconeogenesis in the rat
Authors: MacDonald M , Neufeldt N , Park BN , Berger M , Ruderman N
Published: December 2017

The metabolism of alanine and several other gluconegoneic substrates was studied in anesthtized fed and fasted rats, i.e., rats with low and high rates of gluconeogenesis. Glutamine was released by the hindquarter (muscle) in both groups, whereas lactate, pyruvate, and alanine were taken up in fed rats and were released during starvation. Despite this, blood levels of alanine, lactate, and pyruvate were diminished in fasting rats, suggesting increased extraction by liver. Treatment of fasted rats for 24 h with phloridzin caused glycosuria and secondarily led to hypoglycemia and an intensification of the chargesobserved with fasting, i.e., hyperketonemia, hyperglucagonemia, and increased gluconeogenesis (assessed by urea N excretion). Blood alanine was decreased, even though the release of alanine from muscle was increased. Pretreatment with triamcinolone and administration of exogenous alanine both attenuated the hypoglycemia and ketosis, It is concluded that 1) in states of heightened gluconeogenesis, alanine release from muscle may not keep pace with extraction by liver and blood alanine decreases; 2) the release of alanine, lactate, and pyruvate from muscle parallel each other suggesting common control factors; and 3) in the red state muscle is an important site of lactate disposition.
Osmotic interaction of plasma proteins with interstitial macromolecules
Authors: Wiederhielm CA , Black LL
Published: December 2017

The osmotic interaction of plasma proteins with collagen and hyaluronate has been evaluated by measuring the oncotic pressure of mixed solutions of varying composition. Collagen, despite its insolubility, exhibits a pronounced volume exclusion effect on plasma proteins, and the oncotic pressure of mixed solutions is considerably higher than that of the plasma protein stock solution. The volume exclusion of collagen on small molecules such as sucrose is negligible. A solution composed of 1.6% plasma proteins, 20% collagen, and .4% hyaluronate in Ringer solution, approximating the composition of the interstitium, was found to yield higher oncotic pressures than those previously reported from the interstitium. The probable role of impurities and degradation in the isolation process is discussed. Results reported earlier from in vitro and in vivo studies indicated that tissue oncotic pressures are considerably higher than generally recognized and that tissue fluid is in probable osmotic equilibrium with lymph in skin and muscle.
Effect of dehydration on stimulation of ADH release by heterologous renin infusions in conscious dogs
Authors: Claybauch
Published: December 2017

Unanesthetized dogs were infused with heterologous (hog) renin at 0.33 Goldblatt U/kg per h for 2 h, once normally hydrated and once after 48 h of dehydration. Dehydration increased the average plasma osmolality from 306 to 322 mosmol/kg, the plasma renin activity (PRA) from 0.5 to 1.4 ng/ml per h, and the plasma antidiuretic hormone (ADH) concentration from 1.7 to 3.7 muU/ml, although the latter was not statistically significant. Renin infusion resulted in approximately the same average PRA, about 10 ng/ml per h, in both states of hydration. Mean arterial blood pressure increased during renin infusion in both states of hydration, although the increase was greater when the dogs were normally hydrated. There was no apparent effect of renin infusion on plasma ADH concentration when the dogs were normally hydrated, but in the dehydrated state renin infusion was accompanied by an increase from 3.7 to 6.3 muU/ml in plasma ADH concentrations after 80 min of infusion. There were no apparent changes in plasma osmolality or sodium or potassium concentrations due to the renin infusions; however, plasma osmolality and potassium concentration decreased during the course of the experiment. The results suggest a possible role for the renin-angiotensin system of renin released by the kidney in the control of ADH during dehydration. The metabolic clearance rate of the hog renin was 37 ml/min-kg.
Bicarbonate modulation of glucose-9nduced biphasic insulin release by rat islets
Authors: Henquin JC , Lambert AE
Published: December 2017

The role of HCO3 ions in pancreatic beta-cell functions was evaluated with isolated rat islets. The early phase of insulin release was absent when HCO3 ions were omitted from the medium prior to glucose stimuation, but was augmented if HCO3- withdrawal or reintroduction coincided with glucose increase. The inhibition of the late phase augmented as a function of the duration of HCO3- absence, and its reversibility upon readmission of the anion was delayed. Theophylline and cytochalasin B partially corrected the inhibition of the late phase but failed to restore a rapid response. In the presence of 5 mM NaHCO3, the early response was delayed but the total response was normal. In a HCO3--free medium, glucose oxidation and utilization and glucose transport in islet cells were unaltered. Uptake of calcium was reduced in the absence of HCO3 ions, but normal in 5 mM HCO3-. The results document the importance of HCO3- in insulin release and show that the two phases of glucose-induced secretion are differentially modified by its omission. Some of these findings may be explained by alterations in Ca++ uptake by islet cells. It is suggested that the mechanisms regulating insulin granule extrusion upon stimulation by glucose may be partially different for the two phases of release.
Inhibition of proximal tubular hydrolysis and reabsorption of bradykinin by peptides
Authors: Oparil S , Carone FA , Pullman TN , Nakamura S
Published: December 2017

[3H] bradykinin ([3H] BKN) was microinfused alone or in the presence of a 390- or 780-fold excess of BKN or angiotensin I (AI) into proximal tubules in Inactin-anesthetized rats. Urinary excretion of 3H-labeled material was measured, and intact peptide and its metabolites were identified and quantified. When [3H] BKN was administered with BKN or AI, urinary recovery of 3H-labeled material was increased in a manner directly proportional to tubular length, suggesting that reabsorption of [3H] BKN is related to extent of tubular contact. BKN and AI were equally effective in inhibiting the reabosroption of [3H] BKN and its metabolites from proximal tubular fluid. In contrast, BKN but not AI effectively inhibited the enzymatic hydrolysis of [3H] BKN in the proximal tubule, The data suggest that the proximal tubular mechanism for reabsorbing BKN and its metabolites is of high capacity but not high specificity and that the mechanisms for enzymatic cleavage and reabsorption of BKN and its metabolites may had different specificites and capacities.
Metabolic intermediates and lactate diffusion in active dog skeletal muscle
Authors: Graham TE , Sinclair DG , Chapler CK
Published: December 2017

The concentration of several metabolic intermediates, blood flow (Q), oxygen uptake (VO2), and lactate release (La) were measured in the gastrocnemius muscle of anesthetized dogs. Muscle lactate concentration increased from 1.6 to 2.7 mumol/g wet wt (P less than 0.05) during 0.5-5 min of contractions at 5 twitches/s but was not different from the contralateral resting muscle at 15, 30, or 60 min. Glycerophosphate increased from 0.35 to 0.70 mumol/g wet wt (P less than 0.05) during 0.5-5 min of activity, whereas muscle pyruvate decreased from 0.09 to 0.07 mumol/g wet wt (P less than 0.05). The concentration of NAD did not change in 9 of 11 experiments during contractions, despite a 12- to 15-fold increase in La. Significant decreases in NAD were observed when Q was compromised by arterial occlusion during contractions. No demonstrable relationship existed between La and either the muscle lactate concentration or muscle-venous lactate concentration gradient. Q was positively correlated with both La and muscle lactate during the first 5-15 min of activity. We conclude that increased La or increased lactate concentration in muscle need not be associated with hypoxia and that Q has a major influence on La.
Cat heart acetylcholine: structural proof and distribution
Authors: Brown OM
Published: December 2017

The distribution of acetylcholine (ACh) in the cat heart was investigated by a pyrolysis-gas chromatography (PGC) method. The hearts were dissected into various regions and homogenized in acetonitrile in the presence of propionylcholine, internal standard. Following extraction with toluene and hexane, the choline esters were precipitated as the enneaiodide complex. The isolated choline esters were analyzed by PGC, and the peak corresponding to ACh was quantified. The compound extracted from heart tissue that eluted with the retention time of authentic ACh was identified by mass spectrometry as dimethylaminoethylacetate, the pyrolysis product of ACh. ACh concentrations were found to be higher in the atria than the ventricles. In both the atria and the ventricles, a higher content of ACh was found in the right than the left portions: right ventricle, 5.0 compared to left ventricle, 2.0 nmol/g; and right atrium, 16.8 compared to left atrium, 11.3 nmol/g. Some cats were subjected to a bilateral cervical vagotomy 3 wk before removal and analysis of heart tissue. Hearts from vagotomized cats contained less ACh than controls in the right ventricle (-31%), right atrium (-54%), SA node (-42%), and papillary muscle (-53%), but no decreases were found in the left ventricle, left atrium, or interventricular septum.
Comparison of microelectrode, DMO, and methylamine methods for measuring intracellular pH
Authors: Boron WF , Roos A
Published: December 2017

The intracellular pH (pHi) of giant barnacle muscle fibers was measured with glass microelectrodes and also calculated from the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO) and methylamine (MA). Simultaneously applying any two of these methods to muscle fibers of the same barnacle, we found the pH measured with an intracellular electrode (pH-Elec) to be about 0.06 higher than the DMO-derived pH (pH-DMO), and pH-DMO to be about 0.10 higher than the MA-derived pH (p-ma). in studies on the pHi of squid giant axons, we found that pH-Elec (7.35) and pH-DMO (7.36) were not significantly different. In the barnacle experiments, DMO required about 30 min to reach a steady-state distribution, while MA required more than 5 h. The deviations of pH-DMO and pH-MA from pH-Elec for the barnacle can be explained by a) an error in the assumed intracellular pKa' of DMO or MA, b) membrane permeability to the ionic form of DMO or MA, or c) intracellular compartmentalization. Included is a detailed study of the apparent dissociation constant of DMO as affected by temperature, and ionic strength and composition.
Pathways regulating cardiovascular changes during volume loading in awake dogs
Authors: Bishop VS , Peterson DF
Published: December 2017

The role played by the cardiac sympathetic nerves and arterial baroreceptors in the cardiovascular responses to acute volume loading was studied in conscious dogs. In 15 normally innervated animals, mean arterial pressure rose 10 mmHg, heart rate increased 38 beats/min and cardiac output 1,696 ml/min, while peripheral resistance decreased 0.99 PRU. Neither bilateral baroreceptor denervation, dorsal root sections (T1-T5) or surgical interruption of the left ansa subclavia altered the above responses to acute volume loading. Bilateral section of the ansa subclavia (total cardiac sympathectomy) significantly reduced the heart rate response from 35 +/- 5 to 20 +/- 5 beats/min but did not alter other changes. A similar reduction in heart rate response was observed following selective section of the right ansa subclavia. Intravenous infusions of epinephrine augmented the heart rate response in both normally innervated and cardiac sympathectomized dogs. It is suggested that although the primary efferent pathway for the reflex trachycardia is via the vagus, responses are modulated by sympathetic neural activity. Additionally, the nervous system was not shown to play a measureable role in the observed peripheral resistance changes.
Lipoprotein lipase and uptake of chylomicron triglyceride by skeletal muscle of rats
Authors: Linder C , Chernick SS , Fleck TR , Scow RO
Published: December 2017

Uptake of chylomicron triglyceride and lipoprotein lipase was studied in red and white skeletal muscles, heart, and adipose tissue of rats. Retention of triglyceride fatty acids 10 min after injection was 1.6%/g in heart and adipose tissue, 0.2-0.4%/g in red (soleus and diaphragm) muscles, and 0.1%/g in white (psoas minor) muscles of fed rats. Fasting (24 h) increased retention two- to fourfold in red skeletal muscles and heart, had no effect in white muscles, and decreased retention greater than 75% in adipose tissue. Lipoprotein lipase activity in fed rats was lowest in white muscles and in certain red (posterior belly of digastric and medial head of triceps brachii) musclws, intermediate in soleus and diaphragm muscles and adipose tissue, and highest in heart. Fasting doubled lipoprotein lipase activity in all red skeletal muscles and heart, had no effect in white muscles, and decreased activity 60% in adipose tissue. The findings indicate that triglyceride uptake is related to lipoprotein lipase activity in skeletal muscle and the changes in enzyme activity during fasting divert blood triglyceride to red skeletal muscles.
Interstitial fluid oncotic pressures in rabbit subcutaneous tissue
Authors: Stromberg DD , Wiederhielm CA
Published: December 2017

Interstitial fluid oncotic pressures in rabbit subcutaneous tissues were measured by chronically implanted membrane osmometers. Pairs of osmometers were used, one using a membrane permeable and one impermeable to plasma proteins. Measurements from the small-pore membranes averaged 10.2 mmHg while pressures measured from the large-pore membrane osmometers averaged -1.2 mmHg, indicating that the measured pressures were osmotic rather than hydrostatic in nature. These values are in agreement with previously published values from this laboratory on oncotic pressures of excised rabbit skin and with a computer-simulation study of capillary fluid balance. The oncotic pressures described in this study are of the s-me general magnitude as those of lymph from most organs in the body.
Effectiveness of the aldosterone-sodium and -potassium feedback control system
Authors: Young DB , McCaa RE , Pan UJ , Guyton AC
Published: December 2017

This study was conducted to determine the quantitative importance of the aldosterone feedback mechanism in controlling each one of three major factors that have often been associated with aldosterone, namely, extracellular fluid sodium concentration, extracellular fluid potassium concentration, and extracellular fluid volume. To do this, the ability of the body to control these three factors in the face of marked changes in daily sodium or potassium intake was studied under two conditions: 1) in the normal dog, and 2) in the dog in which the aldosterone feedback mechanism was prevented from functioning by removing the adrenal glands and then providing a continuous fixed level of supportive aldosterone and glucocorticoids during the low and high electrolyte intake periods. Under these conditions, removal of feedback control of aldosterone secretion decreased the effectiveness of plasma potassium control by nearly fivefold (39% vs. 8% change in plasma potassium concentration), fluid volume by sixfold (12% vs. 2% change in sodium space) and had no effect on control of plasma sodium concentration (2% change with and without feedback control of aldosterone secretion.)
Incidence and pathophysiological changes in chronic two-kidney hypertension in the dog
Authors: Watkins BE , Davis JO , Hanson RC , Lohmeier TE , Freeman RH
Published: December 2017

Unilateral renal artery plication in dogs reduced renal blood flow by 80% and produced a sustained elevation in arterial pressure whereas plasma renin activity increased for only 4 days. Sodium was retained for 3 days after plication, but this response is similar to that after a sham operation. Of seven dogs studied chronically, elevated arterial pressure was sustained for 27 days or longer in six animals. In three dogs hypertension continued for 2 mo before collateral vessels developed and arterial pressure fell; ligation of these collaterals restored hypertension. Arterial pressure was unaffected by an infusion of [1-sarcosine, 8-alanine] angiotensin II in chronic hypertensive dogs on a normal sodium intake. This angiotensin antagonist lowered arterial pressure after sodium depletion, but became ineffective following rapid sodium repletion. Chronic hypertensive dogs showed normal responses to deoxycorticosterone acetate. These findings suggest that the renin-angiotensin system is not critically involved in maintenace of chronic two-kidney renovascular hypertension in the dog. The data also show that the homeostatic role played by the renin-angiotensin system in the maintenance of arterial pressure remained intact in chronic hypertension.
Characteristics of phosphate transport in isolated proximal tubule
Authors: Dennis VW , Woodhall PB , Robinson RR
Published: December 2017

The characteristics of inorganic phosphate transport in isolated perfused proximal tubules of the rabbit were examined using radioisotopic techniques. When tubules were perfused with an ultrafiltrate of rabbit serum, the mean lumen-to-bath flux of phosphate in the convoluted segment was 6.60 +/- 1.41 (SE) pmol/mm-min with a simultaneous back-to-lumen flux of 0.45 +/- 0.08. In the straight portion of the proximal tubule, the lumen-to-bath flux was significantly lower (P less than 0.01) at 2.22 +/- 0.48 pmol/min-min with a bath-to-lumen flux of 0.31 +/- 0.05. The lumen-to-bath flux was not affected by increases in the intraluminal phosphate concentration from 2.00 +/- 0.19 to 3.12 +/- 0.34 mM or by the isohydric replacement of bicarbonate in the ambient fluids with chloride. However, phosphate absorption was completely inhibited by ouabain 10(-5) M in the bath. These data indicate that phosphate absorption in these segments occurs by a mechanism other than independent diffusion and is saturated at phosphate concentrations characteristic of normal glomerular filtrate. There is no evidence for significant phosphate transport from bath to lumen.
Bronchial epithelial cells release chemotactic activity for lymphocytes
Authors: Robbins R. A. , Shoji S. , Linder J. , Gossman G. L. , Allington L. A. , Klassen L. W. , Rennard S. I.
Published: December 2017

Lymphocytes can frequently be observed in association with bronchial tissues. One mechanism that might account for this association is that bronchial epithelial cells might release chemotactic factors for lymphocytes. To test this hypothesis, bovine bronchial epithelial cells were cultured in serum-free media, and the supernatant fluids were harvested and evaluated for lymphocyte chemotactic activity using a blind-well chamber technique. Media alone attracted few lymphocytes (12 +/- 2 cells/high power field), but in contrast, there was a significant increase in the number of cells attracted by supernatant fluids obtained from bronchial epithelial cell cultures (40 +/- 6 cells/high power field, P = 0.002). The activity was dose dependent and was demonstrated to be chemotactic activity by checkerboard analysis. Partial characterization of the activity revealed it was not extractable into ethyl acetate but was partially inactivated by trypsin and heat (100 degrees C, 15 min). The responding cells were predominantly T-helper lymphocytes as shown by monoclonal antibody staining, with a smaller proportion being B-lymphocytes. Molecular sieve column chromatography revealed multiple peaks of lymphocyte chemotactic activity, with three of the peaks preferentially attracting T-helper lymphocytes and one of the peaks preferentially attracting B-lymphocytes. These data demonstrate that bronchial epithelial cells can release chemotactic factors for lymphocytes and suggest that bronchial epithelial cells may modulate their local population of immune effector cells.
The search for the cystic fibrosis gene
Authors: Buchwald M. , Tsui L. C. , Riordan J. R.
Published: December 2017

This article reviews progress made to date in the attempt to find the gene causing cystic fibrosis (CF). The search has been focused on a region of the human genome containing no more than 10 genes and has been accomplished in two steps. First, linkage analysis was used to localize the gene to the q31 band of chromosome 7. Subsequently, molecular cloning methods were employed to isolate DNA segments estimated to be within 400,000 base pairs of the CF gene. The current challenge in the research is to find the genes located in this interval and to then prove that one of them is the CF gene. The approaches by which this will be accomplished are discussed.
Peptidase enzymes of the pulmonary vascular surface
Authors: Ryan J. W.
Published: December 2017

No fewer than five peptidase enzymes are disposed on the pulmonary vascular surface and are capable of reacting with peptides (including peptide hormones and pro-hormones) within the intravascular space. The review that follows describes these enzymes and their actions and suggests how the enzymes may be assayed in vivo to improve understanding of pulmonary microvascular functions as well as aspects of endocrinology.
Lung fibroblasts produce chemotactic factors for bronchial epithelial cells
Authors: Shoji S. , Rickard K. A. , Ertl R. F. , Linder J. , Rennard S. I.
Published: December 2017

The interaction between the epithelial cells and the subjacent mesenchymal cells in the airway is thought to play a major role during tissue repair and morphogenesis. To evaluate this interaction, we cultured human lung fibroblasts and bovine bronchial epithelial cells and determined that fibroblast-conditioned medium has chemotactic activity for bronchial epithelial cells. This activity was nondialyzable, heat labile, pepsin labile, acid stable, lipid inextractable, and eluted from Sephadex G-150 column chromatography in the high-molecular-weight range. DEAE-Sephacyl ion exchange and gelatin-Sepharose affinity chromatography revealed two peaks containing chemotactic activity, one of which may be fibronectin, since it binds to gelatin, reacts in a specific immunoassay, and is inhibited of chemotactic activity by anti-fibronectin antiserum, and another of which does not appear to be fibronectin, since it does not bind to gelatin nor react in the immunoassay. Thus lung fibroblasts can produce at least two chemotactic factors for bronchial epithelial cells that may play a role during lung tissue repair and morphogenesis by modulating bronchial epithelial cell migration.
The alpha 1-antitrypsin gene and emphysema
Authors: Perlmutter D. H. , Pierce J. A.
Published: December 2017

alpha 1-Antitrypsin (alpha 1-AT) is the major endogenous inhibitor of neutrophil elastase. Individuals with alpha 1-AT deficiency are susceptible to premature development of emphysema. Thus a greater understanding of this serine proteinase inhibitor (serpin) has been a major objective of research on the pathogenesis of emphysema. In this article, we review recent literature on the alpha 1-AT gene and its relationship to other members of the serpin supergene family, particularly as it pertains to the function of alpha 1-AT. We also discuss the current literature on biosynthesis of alpha 1-AT and how its synthesis may be tightly regulated by the net balance of neutrophil elastase and alpha 1-AT at sites of inflammation/tissue injury. The net functional activity of alpha 1-AT in complex biological fluids is also affected by interaction with other enzymes, inhibitors, matrix proteins, and endogenous oxidants. Finally, we discuss the pathogenesis, clinical manifestations, and treatment of injury to the lung associated with deficiency variants of the alpha 1-AT gene.
Fibroblast-pneumonocyte factor
Authors: Smith B. T. , Post M.
Published: December 2017

Fibroblast-pneumonocyte factor (FPF) is an organ-specific differentiation factor produced, under glucocorticoid regulation, by the fetal lung fibroblast, which in turn enhances the differentiation of the alveolar type II cell with respect to surfactant production. In this article we review the appearance of the type II cell phenotype during fetal life and the action of FPF to time full acquisition of this phenotype. Evidence supporting a physiological role for this factor is reviewed as are details of its production by the fetal lung fibroblast and action on the type II cell. Finally we summarize possible future clinical advantages of using such a material to regulate lung maturation compared with currently used maternal glucocorticoid therapy. These include a more rapid effect and bypassing the inhibition of glucocorticoid action seen in male fetuses and in infants of diabetic mothers.