bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of vasoconstrictors on intestinal vascular resistance and oxygen extraction
Authors: Shepherd AP , Pawlik W , Mailman D , Burks TF , Jacobson ED
Published: December 2017

To delineate the mechanism through which vasoactive compounds alter intestinal oxygen consumption and to determine the pharmacological nature of the receptors involved, we quantitated the effects of vasoconstrictors on arteriovenous oxygen difference and on vascular resistance in isolated constant-flow perfused canine small bowel. Norepinephrine (NE) and sympathetic stimulation (SS) increased vascular resistance and depressed O2 extraction. These effects were not altered by beta-blockade, but were abolished by alpha-blockade. Since capillary filtration coefficients at constant-pressure perfusion and 86Rb extraction at constant flow are reported to diminish during NE and SS, it follows that these agents reduce O2 extraction by an alpha-adrenergic closure of precapillary sphincters. Vasopressin had similar effects which were not affected by adrenergic blocking agents. Epinephrine (Epi) in high doses or after propranolol produced the same effects as NE and SS. By contrast, Epi in low doses increased O2 and 86Rb extraction. This response to low doses of Epi was not affected by phentolamine, but was reversed by propranolol. We conclude that Epi in high doses or after propranolol depresses intestinal O2 extraction by the same mechanism as NE and SS, but the mechanism through which Epi increases intestinal O2 extraction is unclear.
Primate gastric circulation: effects of catecholamines and adrenergic blockade
Authors: Zinner MJ , Kerr JC , Reynolds DG
Published: December 2017

The effects of intra-arterial injections and infusions of epinephrine, norepinephrine, and isoproterenol on gastric blood flow were studied in anesthetized baboons. Blood flow was measured electromagnetically before and after adrenergic blockade. The results for injected epinephrine and norepinephrine indicate these agents to be pure vasoconstrictors in the primate gastric circulation, and this response is attenuated by alpha-adrenergic blockade with phenoxybenzamine. Isoproterenol is a pure vasodilator, and its response is attenuated following beta-adrenergic blockade with propranolol. Intra-arterial infusions of epinephrine and norepinephrine (.05 mug kg-1 min-1) resulted in sustained vasoconstriction with no evidence of autoregulatory escape and no postinfusion "over-shoot." This study suggests that epinephrine and norepinephrine might provide alternatives to vasopressin as a vasoconstrictor for the control of upper gastrointestinal bleeding.
Effect of carbon monoxide on equilibrium between oxygen and hemoglobin
Authors: Okada Y , Tyuma I , Ueda Y , Sugimoto T
Published: December 2017

Oxygen dissociation curves of partially CO-saturated human whole blood drawn freshly or preserved more than 3 wk were studied. With increasing CO-hemoglobin concentrations, oxygen affinity of the blood increased and the Hill coefficient, n, fell and gradually approached unity. The changes induced by CO-hemoglobin showed practically no difference in the presence or absence of 2,3-diphosphoglycerate. The Bohr coefficient, deltalog P50/deltapH, was determined as a function of oxygen saturation for various concentrations of CO-hemoglobin. The coefficient remained essentially unchanged in the presence of CO-hemoglobin. In the presence of less than 50% CO-hemoglobin, a good agreement was observed between the observed oxygen dissociation curves and the curves calculated according to Roughton and Darling (Am. J. Physiol. 141: 17-31, 1944). Based on these results, physiological implications of carboxyhemoglobinemia are discussed quantitatively in comparison with methemoglobinemia.
Ventilatory response to hypercapnia in the larger spotted dogfish Scyliorhinus stellaris
Authors: Randall DJ , Heisler N , Drees F
Published: December 2017

Dogfish were exposed to sudden changes of Pco2 in inspired seawater. During hypercapnia breathing frequency remained constant, but gill ventilation was transiently increased to about 140% of control levels in the 1st h. O2 uptake was significantly increased also, but returned to the initial level before nomalization of gill ventilation. In contrast to the transient rise in gill ventilation and O2 uptake, arterial Po2 was increased for the whole period of hypercapnia. Hypercapnia results in a marked fall in pHa which returned to the initial value in 4-5 h even though hypercapnia is maintained. This rise in pHa with little change in PaCO2 was associated with an increase in plasma bicarbonate concentration. The increase of plasma bicarbonate was in part due to compensatory bicarbonate uptake from the seawater across the gills and in part was effected by transfer between intracellular tissue compartments and extracellular spaces. The compensatory bicarbonate exchange mechanism in the gills seems to have a delay both after onset and termination of hypercapnia.
Vascular response to short-term systemic hypoxia, hypercapnia, and asphyxia in the cat
Authors: Weissman ML , Rubinstein EH , Sonnenschein RR
Published: December 2017

Acute systemic hypoxia, hypercapnia, or asphyxia was produced in ketamine-anesthetized, paralyzed cats by ventilating them for 2-4 min with appropriate gas mixtures. A sustained rise in arterial pressure occurred in all cases. Vascular responses to hypoxia (7% O2, 10% 02, or 14% O2) included muscle constriction, cutaneous (hindpaw) dilatation (no change with 14% O2), renal constriction (unchanged flow), and unchanged intestinal resistance. Asphyxia (hypoxia + 10% CO2) produced a similar pattern, except that intestinal dilatation occurred. Hypercapnia (10% CO2 + 21% O2) produced muscle constriction, renal constriction (unchanged flow), intestinal dilatation, and no change in cutaneous resistance. Intestinal dilatation seemed in all cases a response to elevated CO2 only. Hypercapnia augmented the effects of hypoxia in skin and skeletal muscle. The variation of responses in different vascular beds suggests a patterning of sympathetic discharge, and varying responsivity to local and humoral factors.
Does hyperinsulinemia in ob/ob mice cause an insulin-stimulated adipose tissue?
Authors: Loten EG , Le Marchand Y , Assimacopoulos-Jeannet F , Denton RM , Jeanrenaud B
Published: December 2017

After a 1-h preincubation to remove endogenous insulin, adipose tissue of obese mice (C57BL/L4 ob/ob) had a lower rate of glucose metabolism than tissue which was not preincubated. In contrast, preincubation did not change the metabolism of adipose tissue from lean mice (C57B1/6J +/+). The preincubation effect was abolished in obese mice which had had their serum insulin levels lowered toward normal by streptozotocin treatment. Injection of anti-insulin serum to obese mice caused adipose tissue removed 15 min after the injection to display a rate of glucose metabolsim lower than that of tissue removed before the injection. No such effect was seen in lean mice. These data are consistent with the hypothesis that hyperinsulinemia in the obese mice causes a chronic state of insulin stimulation of their adipose tissue, possibly contributing to their high rates of lipogenesis and their obesity. Several lipogenic enzymes were measured in adipose tissue of both lean and obese mice, and no single enzymatic abnormality was detected which might explain the hyperlipogenesis. Pyruvate dehydrogenase and acetyl-CoA carboxylase were both insulin-sensitive enzymes in lean and obese mice.
Beta-hydroxybutyrate transport in rat brain: developmental and dietary modulations
Authors: Moore TJ , Lione AP , Sugden MC , Regen DM
Published: December 2017

Transport of beta-hydroxybutyrate (betaHB) into rat brain was estimated from the early rise in brain/serum 14C ratio after subcutaneous injection of [14C]betaHB. Permeability of the D isomer exceeded that of the L isomer. Permeability of either isomer rose throughout suckling (sevenfold) and declined after weaning to the low, newborn values. This age dependence differed markedly from those of cerebral blood flow and cerebral permeabilities of urea, glucose, valine, leucine, and DMO (5,5-dimethyloxazolidine-2,4-dione). Fat-feeding more than doubled cerebral betaHB permeability without significantly affecting cerebral blood flow or the permeabilities of urea, glucose, and DMO. Temperature dependence of betaHB permeability was similar to that of glucose transport. The age and diet dependence of betaHB were not accounted for in terms of body temperature, capillary surface, capillary porosity, or plasma proton concentration. A modulable betaHB carrier seemed indicated.Utilization of betaHB by the brain was signficantly governed by permeability, hence the increased permeability in ketotoc states should contribute to glucose sparing and eventually to protein sparing.
Uptake and metabolism of beta-alanine and L-carnosine by rat tissues in vitro: role in nutrition
Authors: Nutzenadel W , Scriver CR
Published: December 2017

Uptake and metabolism of the dipeptide L-carnosine (beta-alanyl-L-histidine) and of the free amino acid beta-alanine were studied in scraped mucosal epithelium of jejunum, kidney cortex slices, and intact hemidiaphragm muscle of the rat. These preparations expose plasma membranes with various orientations to amino nitrogen nutrition.
Regional blood flow in normotensive and spontaneously hypertensive rats
Authors: Nishiyama K , Nishiyama A , Frohlich ED
Published: December 2017

Regional distribution of cardiac output in unanesthetized spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar NR male rats (10 each group; average age 21 wk) was determined using two 15-mum microspheres (141Ce and 85Sr) injected 10 min apart through a left ventricular (LV) cannula. Fractional flow distribution was expressed as percentage activity of injected dose (average of the two measurements). Despite differences in body and organ weights, organ flow distribution did not vary between SHR and WKY, except for heart and testes (P less than 0.025). However, differences did not exist between SHR and NR with respect to heart, brain, lungs, spleen, and adrenal flows (P less than 0.05).
Circadian rhythms of intestinal sucrase and glucose transport: cued by time of feeding
Authors: Stevenson NR , Fierstein JS
Published: December 2017

In the rat, under constant illumination, the activities of the digestive enzyme sucrase and the absorptive transport system for glucose follow circadian rhythms on ad lib. and controlled feeding regimens. In response to controlled feeding, (1400-1800 h or 0200-0600 h, EST), both rhythms shift with time and the general level of activities are enhanced. Sucrase activity peaks before feeding and transport activity peaks during feeding. Feeding is a synchronizer for these digestive-absorptive functions, and the maximum activity of a function may occur prior to as well as subsequent to the daily onset of the synchronizer. The rhythms of these functions results from previous days' feeding patterns.
Erythropoietin production in the rat: additive role of kidney and liver
Authors: Peschle C , Marone G , Genovese A , Magli C , Condorelli M
Published: December 2017

Erythropoietin (Ep) levels were evaluated in serum of neonate, weanling, or adult rats subjected to 1) sham operation, nephrectomy, and/or subtotal hepatectomy and 2) a standard bout of hypoxia (0.45 atm air/6 h, starting 1 h after the operation). Ep activity was quantitated by means of strictly controlled assays in exhypoxic polycythemic mice. The sum of Ep titers in the serum of nephrectomized or hepatectomized rats was compared to Ep levels in sham-operated animals of corresponding age levels, with the exception of 1-wk-old rats: it is relevance that no significant difference is apparent between these Ep production curves. Thus, evidence is presented indicating for the first time that Ep derives from two functionally distinct and additive sources, i.e., the kidney and the liver. Liver Ep, although prevalent in neonatal animals, is obscured in the weanling adult rat by both gradual initiation of massive renal Ep production and progressive decrease of hepatic Ep activity.
Tachypnea after stimulation of afferent cardiac sympathetic nerve fibers
Authors: Uchida Y
Published: December 2017

The role of afferent cardiac sympathetic nerve fibers in the regulation of respiration has been examined. Application of potassium chloride or lactic acid solutions to the left ventricular surface of anesthetized vagotomized dogs resulted in a decrease in the manimum firing rate and shortening in period duration of firing of phrenic nerves. Also, application of the agents caused a decrease in amplitude and an increase in rate of respiratory thoracic movements. The same changes in phrenic nerve activity and respiratory movements were produced by coronary artery occlusion and centrifugal electrical stimulation of the left inferior cardiac nerves. The results indicate tachypnea that can be produced by excitation of afferent cardiac sympathetic nerve fibers.
Open-loop respiratory chemosensitivity in chickens and ducks
Authors: Jones DR , Bamford OS
Published: December 2017

In order to study the behavior of the avian respiratory center under open-loop conditions, recordings of respiratory motor discharges were made from an intercostal nerve in a unidirectionally ventilated paralyzed preparation during normoxic hypercapnia, hypoxic normocapnia and asphyxia, and under control conditions. Respiratory motor burst rate (RMBR) in ducks showed a maximum at 40 mmHg Paco2 with depression at higher and lower values, both in the steady state and during rapid transients. RMBR was apparently independent of Paco2 in chickens, and of Pao2 in both species. During asphyxia, RMBR in ducks fell steadily while the number of spikes in each burst did not change. RMBR during asphyxia bore the same relationship to Paco2 as during unidirectional ventilation. Chickens did not respond consistently to asphyxia, but RMBR tended to increase and, in some cases, the number of spikes per burst also increased. Possible mechanisms and functions of the asphyxic respiratory depression observed in ducks are discussed.
Altered hepatic glycogen metabolism and glucoregulatory hormones during sepsis
Authors: Curnow RT , Rayfield EJ , George DT , Zenser TV , DeRubertis FR
Published: December 2017

Levels of glucose, insulin, and glucagon in portal vein plasma and of liver glycogen and cyclic AMP and activities of glycogen synthase and phosphorylase in liver were assayed in control (CONT) rats and rats infected (INF) with Diplococcus pneumoniae. In INF rats compared with CONT rats, insulin and glucagon levels were higher (8,12,24 h). Activity of synthase I was lower (8, 12, 24 h) and of phosphorylase higher (12 and 24 h) in INF rats. Cyclic AMP levels were higher in INF rats at 12 and 24 h. Total synthase activity was lower in INF rats at 24 h. Glucose given intravenously increased glycogen less in INF than in CONT rats and activated synthase and inactivated phosphorylase in all animals except at 24 h in INF rats. However, in situ perfusion of the livers at 24 h with glucose in buffer decreased phosphorylase activities in all animals and increased synthase I activities in CONT but not INF rats.
Endogenous glucagon regulation in genetically hyperlipemic obese rats
Authors: Eaton RP , Conway M , Schade DS
Published: December 2017

Glucagon concentration and regulation were examined in the Zucker rat, in which obesity and hyperlipemia are phenotypic expressions of an autosomal recessive gene. Using littermate animals which are phenotypically thin and normolipemic as controls, we observed reduced basal plasma glucagon levels in the obese lipemic rats. In response to fasting, obese lipemic animals inappropriately demonstrated a further reduction in plasma glucagon concentration. In response to pharmacologic glucagon stimulation (arginine), a subnormal rise in plasma glucagon concentration was observed in the obese, lipemic animals. Glucagon suppressibility with exogenous glucose remained intact. The reduced secretion of glucagon may be a consequence of the abnormal elevation in concentration of plasma insulin, free fatty acids, and glucose, which are characteristic of the obese, lipemic animal. A possible role of glucagon deficiency in the evolution or maintenance of the lipemic state is suggested.
Ability of exogenous alanine to lower blood beta-hydroxybutyrate during development in rats
Authors: Ozand PT , Tildon JT , Stevenson JH , Reed WD , Cornblath M
Published: December 2017

The intraperitoneal injection of L-alanine into 10- and 21-day-old fed Wistar rats resulted in blood alanine levels of 3-5 mM and in a rapid, significant decrease in the concentration of beta-hydroxybutyrate (betaOHB) in blood. The drop in betaOHB was unrelated to changes in the concentrations of pyruvate, lactate, or glucose. The intraperitoneal injection of glutamate at the same age had no effect on betaOHB values. In 2-day-old pups and in older weaned animals, the injection of alanine had either no effect or increased the levels of betaOHB in blood. The most rapid disappearance of exogenous alanine occurred in 35-day-old and not in 10- and 21-day-old rats. These data suggest that alanine has a depressant effect on the level of circulating betaOHB at a specific stage in the animal's maturation.
Forelimb blood flow distribution during hypothalamic dilator response
Authors: Menninger RP , Baker CH
Published: December 2017

An attempt is made to determine whether hypothalamically induced forelimb vascular dilation in the dog affects primarily exchange beds or shunt circuits. Slug injections of [131I] albumin and 86RbCl were used to measure the active vascular volume of the forelimbs and permeability surface area product (PS), respectively. Changes in total vascular volume (TVV), filtration, and capillary filtration coefficient (CFD) were measured by plethysmography. During stimulation, forelimb blood flow increased 25% and TVV increased an average 1.5 ml. There was no plethysmographic evidence of outward capillary filtration. Active vascular volume decreased 11%. PS decreased 11%, and CFC decreased 20%. These results point to a redistribution of blood flow from exchange circuits to faster flow channels. During constant-inflow perfusion, there was evidence from CFC and PS measurements that the capillary surface area was increased while active vascular volume decreased. The results observed with hypothalamic stimulation are different from those obtained with pharmacologic dilators and denervation. It is suggested that the former method has a more selective effect in lowering resistance in the faster shuntlike vessels.
Similarities in coronary flow between external counterpulsation and intra-aortic balloon pumping
Authors: Watson JT , Platt MR , Rogers DE , Sugg WL , Willerson JT
Published: December 2017

The ability of external counterpulsation (Cardiassist) and intra-aortic balloon pumping (AVCO) to influence collateral coronary blood flow in ischemic myocardium was measured in anesthetized dogs. Cardiac output and heart rate (atrial pacing) were held constant on right-heart bypass. Both external counterpulsation and balloon pumping augmented peak diastolic pressure (30 mmHg and 38 mmHg, respectively), while mean aortic pressure, peak left-ventricular pressure, left-ventricular end-diastolic pressure, maximum left-ventricular dp/dt, hematocrit, and osmolality remained unchanged. Regional coronary blood flow was measured using 9-mum radioactive microspheres. External counterpulsation and balloon pumping begun immediately following ligation of the left-anterior descending coronary artery significantly increased collateral coronary blood flow 29 +/- 7.5% (SE, P is less than .01) and 20 +/- 8% (P is less than .05), respectively, to ischemic myocardium. This redistribution of collateral coronary blood flow produced by both methods of counterpulsation was primarily to the subepicardial region of the ischemic myocardium. The mechanism responsible for the measured increases in collateral coronary blood flow appears most likely to be an increased pressure gradient produced by diastolic augmentation.
Uric acid excretion by the pig kidney
Authors: Simmonds HA , Hatfield PJ , Cameron JS , Cadenhead A
Published: December 2017

The handling of uric acid by the pig kidney has been investigated during continuous urate infusion in unrestrained, unanesthetized animals. Urate-to-inulin clearance rates in excess of 1 were found under all experimental conditions, demonstrating only net secretion by the pig kidney. The demonstration of a secretory maximum was precluded owing to a progressive reduction in the GFR associated with high rates of urate infusion. Urate clearance was independent of urine flow rate up to 10 ml/min. The administration of probenecid inhibited urate secretion, but urate-to-inulin clearance ratios below unity were not observed. Pyrazinamide or pyrazinoic acid, at doses which either inhibited secretion or promoted uricosuria in other species, did not alter urate excretion in the pig. Probenecid together with pyrazinamide exerted the same inhibitory effect on urate secretion as probenecid alone. Pyrazinoic acid was reabsorbed at all infusion rates. It is concluded that the pig kidney eliminates uric acid by filtration and secretion only.
Metering of fluid intake and determinants of ad libitum drinking in rats
Authors: Rowland N , Nicolaidis S
Published: December 2017

The contributions of homeostatis mechanisms to spontaneous drinking were assessed in a study of residual oral drinking under several conditions of exogenous water administration. Continuous and/or discontinuous infusiors were conducted for long periods with dry food present ad libitum. The routes of administration were intravenous (IV), intragastric (IG) through a nasopharyngeal catheter. All infusions reduced from noninfused levels, but the magnitude of that reduction was a function of both route and temporal characteristics. Continuous infusions were more effective via the IG route than IV, and a residual intake of about 10 ml/24 h presisted at even the highest infusion rates. Discontinuous meal-paired IV infusions suppressed mid- and postmeal drinking, consistent with the satisfaction of systemic needs induced by cry food intake. Meal-paired IG nasopharyngeal infusions competely suppressed drinking when the infusions exceeded base-line intake by only about 20%. In marked contrast, corresponding IG infusions through a direct fistula catheter were relatively ineffective. In all cases the decreases in drinking were not of a nonspecific nature beacuse food intake was unchanged. The discussion considers the different levels of metering involved and the time-varying (derivative) nature of the infusion if was suggested that there is a nonhomeostatic contribution to normal drinking.
Arachidonic acid in splanchnic artery occlusion shock
Authors: Bridenbaugh GA , Flynn JT , Lefer AM
Published: December 2017

Arachindonic acid infused into the mesenteric vascular bed of normal pentobarbital-anesthetized dogs at a concentrations of 150 mug/kg per min produced no significant changes in mean arterial blood pressure (MABP), portal vein pressure (PVP), screen filtration pressure (SFP), platelet count, circulating lysosomal enzyme or myocardial depressant factor (MCF) activities, nad only modestly increased superior mesenteric arter flow (SMAF)ans endogenous prostaglandin concentrations concentrations. It is concluded that arachidonic acid, at the infusion rate employed, dose not have any major effect on the circulatory status or on the lysosomal or platelet stability in normal dogs. In contrast, arachidonic acid administered to dogs in splanchnic artery occulusion (SAO) shock significantly exacerbated the decline in MABP seen after release of the occlusive clamps and also significantly reduced mesenteric blood flow. The hypothnsive of arachidonic acid appears to be partly due to the fatty acid itself and partly due to the metavolically formed prostaglandin endoct the platelet count or aggregability, lysosomal hydrolase activity, or MDF formation in the SAO shock dogs. These data suggest that increased endogenous prostaglandin concentrations in themselves are not a prime factor in the pathophysiology of circulatory shock, but that endogenous prostaglandin or related substances can significantly modulate the shock state.
Intestinal ion transport: effect of norepinephrine, pilocarpine, and atropine
Authors: Hubel KA
Published: December 2017

The effects of parenteral pilocarpine, atropine, and norepinephrine on salt and water transport were studied in jejunum and ileum of anesthetized rats. Pilocarpine increased jejunal transmural PD, reduced absorption of Na, K, HCO3, and H2O, and increased secretion of Cl; in ileum, it caused secretion of Na and H2O, elicited secretion of K, and reduced the absorption of Cl. In both segments, perfusate became more akaline, and there was less of a rise in PCO2. Atropine prevented all changes caused by pilocarpine. Atropine alone increased jejunal absorption of Na and HCO3 and acidity of perfusate, implying that cholinergic nerves influence transport. Norepinephrine augmented jejunal absorption of Na, Cl, and H2O but caused no change in PD. In ileum, norepinephrine increased absorption of Na and Cl, reduced the rise in pH, increased the rise in PCO2 of perfusate, but did not affect net HCO3 movement. With all agents, when Na absorption increased, perfusate became more acidic in jejunum and less alkaline in ileum, evidence of an association between Na and H transport.
Hypoglycemic depression of RES function
Authors: Buchanan BJ , Filkins JP
Published: December 2017

The intravascular removal rates of colloidal carbon and of biologically active endotoxin by the reticuloendothelial system (RES) were evaluated as a function of blood-glucose levels. There was a significant negative correlation of carbon clearance half time on blood glucose in both saline-treated and insulin-treated rats. Insulin hypoglycemia depressed RES carbon clearance with the maximal effect occurring at blood glucose values below 30 mg/dl. Insulin hypoglycemia also severely impaired the intravascular removal of endotoxin as evaluated by lethality bioassay in lead-sensitized rats. It is concluded that blood glucose may modulate RES phagocytic function and that the hypoglycemia of endotoxin shock may augment the shock state due to impairment of RES host defense clearance functions.
Hypothalamic and thalamic blood flow during somatic afferent stimulation in dogs
Authors: Sandor P , Demchenko IT , Kovach AG , Moskalenko YE
Published: December 2017

The effect of somatic afferent C fiber stimulation on regional cerebral blood flow (rCBF) and cerebral tissue available oxygen (aO2) was studied in 20 dogs under chloralose anesthesia. Mean arterial blood pressure, arterial Pco2, and pH were stabilized before and during the 3-min stimulation of the sciatic nerves (20 V, 300 ms, 15 Hz). Combined gold+platinum electrodes were chronically implanted into the ventral posterolateral nucleus of the thalamus, ventromedial nucleus of the hypothalamus, and into the white matter. Tissue aO2 and rCBF of these regions were measured polarographically, the latter by the H2-gas clearance technique. Blood flow changed from 42 +/- 2.1 to 28 +/- 1.7 ml/100 g per min (cerebrovascular resistance (CVR), from 2.91 +/- 0.29 to 4.31 +/- 0.52 resistance units (RU) in the thalamus, from 59 +/- 5.0 to 47 +/- 5.0 ml/100 g per min (CVR: from 2.46 +/- 0.28 to 2.92 +/- 0.35 RU) in the hypothalamus, and from 21 +/- 1.0 to 17 +/- 0.8 ml/100 g per min (CVR: from 6.367 +/- 0.35 to 7.672 +/- 0.40 RU) in the white matter during ipsilateral stimulation. Contralateral stimulation of the sciatic nerves caused a more moderate but likewise significant drop in rCBF and an increase in CVR except in the white matter. Parallel to these changes, tissue aO2 decreased by 25 +/- 2% in the thalamic and by 19 +/- 2% in the hypothalamic area, relative to the prestimulation level.
Intestinal mucosal cyclic GMP: regulation and relation to ion transport
Authors: Brasitus TA , Field M , Kimberg DV
Published: December 2017

Stimulation of alpha-adrenergic and muscarinic cholinergic receptors in rabbit ileal mucosa in vitro produced 5- to 15-fold increases in cyclic GMP (cGMP) concentration that were maximal within 2 min and gone within 30 min. Cholecystokinin octapeptide and insulin caused similar increases in cGMP. None of these agents affected cAMP. The epinephrine-induced increase in cGMP was blocked by atropine at 100 but not at 1 muM concentration. Epinephrine stimulates active NaCl absorption and decreases short-circuit current (SCC) in vitro, the latter effect due to inhibition of HCO3 secretion. Atropine (100 muM) blocked the former but not the latter effect of epinephrine. In vitro additions of several concentrations of cGMP and 8-bromo-cGMP did not decrease SCC or alter Na fluxes. Thus, changes in cGMP concentration have been directly correlated with changes in active absorption of NaCl, but a causal relationship has not been proven.
Fibrin-induced release of platelet serotonin
Authors: Orloff KG , Michaeli D
Published: December 2017

Human platelets were reacted with polymerized fibrin formed from human fibrinogen. The platelets adhered to the fibrin particles and this adhesion was followed by the release of serotonin from prelabeled platelets. The adhesion of platelets to fibrin was not inhibited by adenosine or prostaglandin E1. However, the subsequent Ca2+-dependent release of platelet serotonin was completely inhibited by these compounds. After the initial platelet-fibrin interaction, ADP and serotonin released from activated platelets may lead to additional platelet aggregation and release. Therefore, in addition to clot stabilization, fibrin serves as an initiator of the platelet release reaction. This in turn initiates the self-amplifying process of platelet aggregation.
Interorgan transport of amino acids in hemorrhagic shock
Authors: Elwyn DH , Parikh HC , Stahr LJ , Kim SI , Shoemaker WC
Published: December 2017

Arterial concentrations and net organ metabolism of amino acids (AA), O2, CO2, H+, and glucose (Glc) were measured in two dogs before and during hemorrhage and after blood replacement. Shock caused increased splanchnic and decreased peripheral blood flow and O2 consumption. Po2 decreased more in hepatic venous than in mixed venous blood. pH fell in hemorrhage and increased with retransfusion. Increased liver output and arterial concentration of Glc were observed during hemorrhage. Differences between animals correlated with nutritional status. Blood concentrations of most AA showed little change during hemorrhage but increased after retransfusion. In contrast, arginine concentrations declined sharply. Peripheral output and hepatic uptake of most AA occurred during the control period. During shock, peripheral output and hepatic uptake of total AA and most individual AA declined progressively; after retransfusion peripheral uptake and hepatic output of many AA occurred. By contrast, peripheral output and hepatic uptake increased for alanine, glutamine, serine, phenylalanine, and tyrosine. After retransfusion net transport of some compounds occurred from periphery to liver; others, from liver to periphery. During shock, hepatic protein catabolism increased. and this catabolism, accompanied by decreased hepatic uptake (increased hepatic output), seemed the main cause of increased blood AA concentrations. Protein catabolism in peripheral tissue was not a cause of increased blood concentrations. Pathological changes in pH, Po2, and blood flow, occurred early in hemorrhage. In contrast, changes in AA movements and concentrations were within normal limits until late in shock.
Renal urate excretion at various plasma concentrations in the rat: a free-flow micropuncture study
Authors: De Rougemont D , Henchoz M , Roch-Ramel F
Published: December 2017

Free-flow micropuncture experiments were performed in male Sprague-Dawley rats undergoing moderate mannitol diuresis and infused with urate-containing solutions. The resulting plasma urate concentrations ranged from 37.5 +/- 2.4 to 601.2 +/- 23.8 muM. With urate loading, the fraction of filtered urate excreted in pelvic urine increased from 0.32 +/- 0.02 to 0.92 +/- 0.05 mu M, but net secretion was not observed. At normal urate levels net reabsorption occurred along superficial proximal tubules, whereas net secretion could be demonstrated at the highest plasma urate levels. Net movements of urate did not appear to occur across the walls of the lower segments of nephrons.
Effect of potassium depletion on cerebrospinal fluid bicarbonate homeostasis
Authors: Nattie EE , Tenney SM
Published: December 2017

We have examined the effect of K depletion on CSF [HCO3-] homeostasis in awake rats. The relationship of CSF [HCO3-] to arterial [HCO3-] in metabolic acid-base disturbances is displaced is an upward direction and has a significantly increased slope in K-depleted vs. control rats (0.51 +/- 0.02 vs. 0.42 +/- 0.02). Results of partial K-repletion experiments, with peripheral acid-base balance held constant, suggest that the effect is K specific. The K-depleted animals also exhibit a wider (CSF-arterial) PCO2 difference than controls (11.1 vs. 8.4 mmHg). When CSF [HCO3-] is shown as a function of CSF PCO2 the data of K-depleted rats are no longer displaced when compared to controls but still have a significantly greater slope (1.21 +/- 0.23 vs. 0.89 +/- 0.08). This increased slope is interpreted to reflect enhanced HCO3- movement from blood to CSF at high arterial [HCO3-]. Analysis of our data and observations from the literature in conditions of mixed acid-base disturbances suggest that CSF [HCO3-] is determined by a) CSF PCO2 and b) the level of arterial [HCO3-] when the latter is greater than the normal CSF [HCO3-].
Canine gut receptors mediating pancreatic responses to luminal L-amino acids
Authors: Meyer JH , Kelly GA , Spingola LJ , Jones RS
Published: December 2017

Pancreatic protein and bicarbonate outputs were measured in dogs with pancreatic fistulas receiving intravenous secretin while individual L-amino acids or mixtures of L-amino acids were perfused into proximal intestine, Both phenylalanine and tryptophan were potent stimuli of pancreatic secretion; alanine, leucine, and valine increased protein outputs but their effects were small and not statistically significant. Six other amino acids were ineffective. Tryptophan perfused together with phenylalanine augmented responses to phenylalanine; methionine, ineffective when perfused alone, did not alter responses to phenylalanine when perfused with the latter. Responses to phenylalanine perfused at concentrations above 8 mM were dependent on load and were mediated by lengths of proximal bowel greater than 10 cm.
Mechanisms of temperature regulation in heat-acclimated hamsters
Authors: Jones SB , Musacchia XJ , Tempel GE
Published: December 2017

Mechanisms of temperature regulation were assessed by measurements of oxygen consumption (VO2), body temperature (Rre = rectal, Tsk = skin), evaporative water loss (EWL), regional distribution of blood flow, and blood volume. Hamsters (Mesocricetus auratus) were acclimated to ambient temperatures of 34 or 22 degrees C. VO2 of 34 degrees C-exposed animals was reduced to 50% of that of controls at 22 degrees C, whereas EWL with heat exposure was almost double that of controls. Heat-acclimated animals had a slightly elevated Tre in comparison to 22 degrees C-acclimated animals, whereas there was a marked elevation in Tsk with heat exposure, in contrast to control animals at 22 degrees C. Blood flow distribution measurements indicated that with 34 degrees C exposure there was a decreased flow in liver, kidney, and intestine, whereas there was an increase to the carcass. Red cell and plasma volumes in heat-acclimated hamsters were decreased belwo the values of the 22 degrees C controls. Heat acclimation of the fhamster appears to involve reduced VO2 and increased WEL. Convective and radiative heat loss appear to be maintained by increased Tsk with heat exposure. Nonevaporative heat dissipation mechanisms are of primary importance in thermoregulation of the heat-acclimated hamster, and it is suggested that this is mediated by increased peripheral blood flow with reduced flow to the viscera.
Glucose and bicarbonate reabsorption in edematous dogs
Authors: Arruda JA , Westenfelder C , Lockwood R , Kurtzman NA
Published: December 2017

Glucose and bicarbonate reabsorption were studied in dogs made edematour by aortocaval fistula (A-V dogs) and in sham-operated dogs. Following construction of the A-V fistula, there was a significant increase in body weight; glomerular filtration rate, renal plasma flow, hematocrit, and sodium excretion decreased significantly. Bicarbonate reabosorption was significantly higher in A-V than in sham dogs both during control and volume expansion. Volume expansion depressed bicarbonate reabsorption significantly in both groups. Glucose reabsorption fell following volume expansion in both groups; glucose reabsorption was significantly higher in A-V dogs than in sham dogs during control and volume expansion. Volume expansion led to a minimal increase in sodium excretion in A-V dogs when compared to the increase in the sham dogs. These data demonsttate that chronic sodium retention is associated with enhanced reabsorption of glucose and bicarbonate. The site in the neophron responsible for the increase in reabsorption of these substances cannot be determined with certainty based on these clearance studies although it is possible that proximal reabsorption may be enhanced in this model.
Development of the renal response to blood volume expansion in normal and fast-growing rats
Authors: Bengele HH , Solomon S
Published: December 2017

Male rats from reduced (fast-growing) litters between 14 and 50 days of age were studied. Standard renal clearnce techniques were employed. After a 60-min control period, the animals were infused (2.3% body wt) with heparinized donor blood obtained from lillermates of the same age. Renal function was followed for an additional 60 min. The efficiency of the diuretic response, the percent infused volume excreted above control levels, and the sodium efficiency, the percent infused Na excreted, were calculated. Results indicate that both efficiencies develop in a discontinuous pattern and that they are comparable. This pattern of development, as well as the magnitude of the mature response, is comparable to that previously reported for rats from intact (normally growing) litters. The onset and attainment of the mature response is, however, shifted in time, such that reduced-litter animals achieve the mature response 10-15 days earlier than intact-litter rats. Results exclude chronological age or body weight alone as principal determinant of the mature response and suggest that some function of growth rate is responsible for the maturation of this regulatory function.
Bronchial epithelial cells release chemoattractant activity for monocytes
Authors: Koyama S. , Rennard S. I. , Shoji S. , Romberger D. , Linder J. , Ertl R. , Robbins R. A.
Published: December 2017

Lung macrophages are monocyte-derived cells that play a central and essential part in local immunity. Because the bronchial epithelial cells that line the airway can modulate their local cellular environment by releasing chemotactic factors for neutrophils, lymphocytes, and fibroblasts, we postulated that the bronchial epithelial cells might release chemotactic activity for monocytes. To test this hypothesis, bovine bronchial epithelial cells were isolated and cultured. The supernatant fluids were collected at 12, 24, 36, 48, 72, 96, and 120 h and evaluated for monocyte chemotactic activity, using a blind-well chamber technique. The supernatant fluids possessed significantly greater chemotactic activity than medium alone, with optimal migration contained in supernatant fluids harvested at 72 h (5.8 +/- 2.3 vs. 39.8 +/- 2.8 cells/high-power field, P less than 0.001). Partial characterization of the released monocyte chemotactic activity revealed that the cells released a low-molecular-weight lipid-soluble chemotactic factor after 24 h in culture, but in contrast, a high-molecular-weight protein chemokinetic factor was released after 72 h in culture. These findings suggest that bronchial epithelial cells may release chemotactic activity for, and thus may modulate the recruitment of, monocytes into bronchial passages.
Regulation of cellular glutathione
Authors: Deneke S. M. , Fanburg B. L.
Published: December 2017

In addition to its participation in a variety of other biochemical reactions, glutathione (GSH) is a major antioxidant. It is regularly generated intracellularly from its oxidized form by glutathione reductase activity that is coupled with a series of interrelated reactions. Synthesis of GSH also takes place intracellularly by a two-step reaction, the first of which is catalyzed by rate-limiting gamma-glutamylcysteine synthetase activity. Intracellular substrates for GSH are provided both by direct amino acid transport and by a gamma-glutamyl transpeptidase reaction that salvages circulating GSH by coupling the gamma-glutamyl moiety to a suitable amino acid acceptor for transport into the cell. Although the liver is a net synthesizer of circulating GSH, organs such as the kidney salvage GSH through the gamma-glutamyl transpeptidase reaction. Intracellular GSH may be consumed by GSH transferase reactions that conjugate GSH with certain xenobiotics. Elevation of cellular GSH levels in cultured cells in response to hyperoxia or electrophilic agents such as diethylmaleate is coupled with an increase in activity of the Xc- transport system for the amino acids cystine and glutamate. Strategies may be developed for protection against oxidant injury by enhancement of transport systems for precursor amino acids of GSH or by providing substrate that circumvents feedback inhibition of GSH synthesis.
Fatty acid biosynthesis in developing fetal lung
Authors: Rooney S. A.
Published: December 2017

Fatty acids are integral components of glycerolipids and hence of the phosphatidylcholine-rich pulmonary surfactant. There is ample evidence that the lung is able to synthesize fatty acids de novo. Toward the end of gestation as the fetus prepares for life outside the uterus, there is a surge in phosphatidylcholine synthesis. At the same time there is an increase in de novo fatty acid biosynthesis as well as in the activity of fatty acid synthase, the enzyme that catalyzes the final steps in fatty acid synthesis. Glucocorticoids have long been known to accelerate phosphatidylcholine biosynthesis in the fetal lung and they have also been found to stimulate fatty acid biosynthesis and fatty acid synthase activity. In fact, fatty acid synthase is the first, and so far the only, enzyme involved in lipid biosynthesis to be clearly identified as glucocorticoid inducible in fetal lung. De novo fatty acid biosynthesis may have two important roles relating to surfactant production during late fetal life. In addition to providing fatty acids for incorporation into surfactant phospholipids, recent data suggest that fatty acids may also directly regulate phosphatidylcholine biosynthesis by activation of choline-phosphate cytidylyltransferase, an enzyme catalyzing a rate-limiting step in its biosynthetic pathway.
Short-term perinatal 10% O2 alters postnatal development of lung alveoli
Authors: Massaro G. D. , Olivier J. , Massaro D.
Published: December 2017

We studied the effect of breathing 10% O2 for less than or equal to 9 h by rat dams during the last day of gestation and (with their pups) for 1-2 h immediately after birth on the development of the lung's gas exchange region in the pups. Our major finding is that this brief stress resulted in substantially altered lung development noted at age 7 days and still partially present at age 30 days. In particular, perinatal hypoxia slowed the postnatal increase of lung volume, delayed septation of the large gas exchange saccules, diminished the increase of the gas exchange surface area, but accelerated thinning of the wall of the gas exchange structures. The changes produced by briefly breathing 10% O2 had as great an effect on these aspects of lung development as the same prenatal exposure to 10% O2 plus continuous postnatal exposure to 10% O2 for 7 days. Breathing 10% O2 had a particularly strong effect on alveolar wall thinning, since 2 h of breathing 10% O2 immediately after birth, without prenatal hypoxia, accelerated thinning of the alveolar wall.
Secretagogues for lung surfactant increase lung uptake of alveolar phospholipids
Authors: Fisher A. B. , Dodia C. , Chander A.
Published: December 2017

This study evaluated the effect of known secretagogues for lung surfactant on the uptake of phospholipid from the aveolar space. Synthetic liposomes containing tracer [choline-methyl-3H]dipalmitoyl phosphatidylcholine (DPPC) were instilled endotracheally in anesthetized rats. Lungs were then isolated and perfused under control conditions or with addition of terbutaline (0.1 mM), ATP (1 mM), or a phorbol ester, tradecanoyl phorbol acetate (TPA, 30 ng/ml). Uptake of liposomes was defined as lavage-resistant accumulation of radioactivity in the lung. Uptake at 2 h was 18.2 +/- 0.93% of instilled radioactivity per minute (mean +/- SE, n = 4) under control conditions and was increased by 56-82% in the presence of each of the agonists (P less than 0.05). At 5 min after addition of terbutaline, uptake was unchanged but secretion of phosphatidylcholine (PC) into the alveolar space was significantly stimulated. Internalized diphosphatidylcholine was degraded to aqueous soluble metabolites and also converted to PC containing an unsaturated fatty acid, and this metabolism was significantly stimulated in the presence of each of the secretagogues. These results indicate that known secretagogues for surfactant increase uptake and metabolism of phospholipid, suggesting linkage of these processes in a physiologically regulated surfactant cycle.
Cellular and molecular mechanisms of chemical synaptic transmission
Authors: Millhorn D. E. , Bayliss D. A. , Erickson J. T. , Gallman E. A. , Szymeczek C. L. , Czyzyk-Krzeska M. , Dean J. B.
Published: December 2017

During the last decade much progress has been made in understanding the cellular and molecular mechanisms by which nerve cells communicate with each other and nonneural (e.g., muscle) target tissue. This review is intended to provide the reader with an account of this work. We begin with an historical overview of research on cell-to-cell communication and then discuss recent developments that, in some instances, have led to dramatic changes in the concept of synaptic transmission. For instance, the finding that single neurons often contain multiple messengers (i.e., neurotransmitters) invalidated the long-held theory (i.e., Dale's Law) that individual neurons contain and release one and only one type of neurotransmitter. Moreover, the last decade witnessed the inclusion of an entire group of compounds, the neuropeptides, as messenger molecules. Enormous progress has also been made in elucidating postsynaptic receptor complexes and biochemical intermediaries involved in synaptic transmission. Here the development of recombinant DNA technology has made it possible to clone and determine the molecular structure for a number of receptors. This information has been used to gain insight into how these receptors function either as a ligand-gated channel or as a G protein-linked ligand recognition molecule. Perhaps the most progress made during this era was in understanding the molecular linkage of G protein-linked receptors to intramembranous and cytoplasmic macromolecules involved in signal amplification and transduction. We conclude with a brief discussion of how synaptic transmission leads to immediate alterations in the electrical activity and, in some cases, to a change in phenotype by altering gene expression. These alterations in cellular behavior are believed to be mediated by phosphoproteins, the final biochemical product of signal transduction.