bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered heart rate baroreflex during pregnancy: role of sympathetic and parasympathetic nervous systems
Authors: Brooks V. L. , Kane C. M. , Van Winkle D. M.
Published: December 2017

Two studies were performed to determine whether the attenuation of baroreflex control of heart rate during late pregnancy in conscious rabbits is due to changes in parasympathetic (Para) or sympathetic (Sym) control of the heart. In the first, baroreflex relationships between arterial pressure and heart rate were generated before and after treatment with propranolol (Pro) to block Sym or with methscopolamine (Meth) to block Para. Each rabbit was studied in both the pregnant and nonpregnant state. Pregnancy decreased maximum baroreflex gain from 14.9 +/- 4.0 to 4.8 +/- 0.9 beats.min-1.mmHg-1 (P < 0.01) and decreased heart rate range from 177 +/- 6 to 143 +/- 10 beats/min (P < 0.01), primarily by increasing minimum heart rate (114 +/- 6 to 134 +/- 8 beats/min; P < 0.01). The difference between pregnant and nonpregnant rabbits in baroreflex gain was not altered by Meth but was abolished by Pro, suggesting that it is due to decreased Sym control of the heart. The elevated minimum heart rate of pregnancy persisted after Pro, but was abolished by Meth, suggesting that it is mediated by decreased Para control of the heart. In the second study, isolated buffer-perfused hearts from pregnant and nonpregnant rabbits were treated with increasing doses of isoproterenol (0.3-300 mM) or acetylcholine (0.3-10,000 microM), and the heart rate responses were determined. Hearts from pregnant rabbits were more sensitive to isoproterenol (P < 0.05), but less responsive to acetylcholine (P < 0.05). In conclusion, pregnancy-induced decreases in cardiac reflex gain and range appear to be mediated by alterations in Sym and Para, respectively. The change in Sym occurs proximal to the heart, whereas the decreased contribution of Para may be due, at least in part, to decreased sensitivity of the heart to acetylcholine.
Fetal grafts containing suprachiasmatic nuclei restore the diurnal rhythm of CRH and POMC mRNA in aging rats
Authors: Cai Aihua , Scarbrough Kathryn , Hinkle David A. , Wise Phyllis M.
Published: December 2017

We assessed whether fetal tissue containing the suprachiasmatic nuclei (SCN) can restore age-related changes in the diurnal rhythm of hypothalamic corticotropin-releasing hormone (CRH) and anterior pituitary proopiomelanocortin (POMC) mRNA. Young, middle-aged, and middle-aged SCN-transplanted rats were killed at seven times of day. In young rats, CRH mRNA exhibited a diurnal rhythm in the dorsomedial paraventricular nuclei but not in other subdivisions of the nuclei. No rhythm was detected in aging rats. SCN transplants restored a rhythm in CRH mRNA, but the timing was not precisely the same as in young animals. POMC mRNA exhibited a daily rhythm in young rats. Aging abolished the rhythm and decreased the average mRNA level; fetal transplants restored the rhythm, but the amplitude remained attenuated. These data are the first demonstration that fetal tissue can restore the diurnal rhythm of a neuroendocrine axis that is driven by the SCN. We conclude that the neuroendocrine substrate from the aging host remains capable of responding to diurnal cues to express diurnal rhythmicity in CRH/POMC mRNA when fetal SCN transplants confer the appropriate signals.
Glucocorticoid-induced renal vasodilatation is mediated by a direct renal action involving nitric oxide
Authors: De Matteo R. , May C. N.
Published: December 2017

Glucocorticoids increase renal blood flow (RBF) and glomerular filtration rate, but the mechanisms are unclear. We investigated whether the cortisol-induced increment in RBF is a direct renal action or secondary to its systemic effects and whether nitric oxide (NO) plays a role in this response. In conscious sheep, cortisol infused intravenously (5.0 mg/h) or into the renal artery (1.3 mg/h) for 5 h increased RBF by 66 ± 8 and 53 ± 11 ml/min, respectively. Plasma glucose was increased by intravenous cortisol (0.4 ± 0.1 mmol/l) but not by intrarenal cortisol. Renal vein plasma cortisol levels were similar at the end of each infusion (193 ± 31 intravenously; 151 ± 25 nmol/l intrarenal), but systemic levels were different (277 ± 31 intravenous; 69 ± 10 nmol/l intrarenal). Inhibition of NO synthesis by N ω-nitro-l-arginine infused intravenously (10 mg/kg followed by 5 mg ⋅ kg−1 ⋅ h−1) or intrarenally (2 mg ⋅ kg−1 ⋅ h−1) significantly reduced the cortisol-induced renal vasodilatation. In contrast, constriction of the renal vasculature with intrarenal angiotensin (0.3 μg/h) did not prevent the cortisol-induced renal vasodilatation. These findings demonstrate that cortisol acts directly on the kidney to cause renal vasodilatation and to increase RBF and suggest that this response involves the endothelium-derived relaxing factor NO.
Cardiac afferents play the dominant role in renal nerve inhibition elicited by volume expansion in the rabbit
Authors: Badoer Emilio , Moguilevski Viatcheslav , McGrath Barry P.
Published: December 2017

In the rabbit, vagotomy combined with arterial baroreceptor denervation abolishes the renal sympathoinhibition elicited by volume expansion. However, the effect of removing cardiopulmonary afferents alone has not been investigated. The aim of the present study was to determine the role of the cardiac afferents in the renal sympathetic response elicited by volume expansion in the normal conscious rabbit. Four experimental groups were used in which rabbits were administered 1) volume expansion (Haemaccel, 1.9 ml/min for 60 min), 2) volume expansion + bolus intrapericardial procaine (20 mg) to block cardiac afferents, 3) volume expansion + intravenous procaine (20 mg bolus), and 4) intrapericardial procaine alone (20 mg bolus). Volume expansion did not significantly affect mean arterial pressure or heart rate but produced a profound fall in renal sympathetic nerve activity (∼50%). Intrapericardial procaine administered 30 min after the start of volume expansion markedly reversed the renal sympathoinhibition to within 20% of the pre-volume expansion level, an effect that wore off over 25 min. In contrast, intravenous procaine lowered renal sympathetic nerve activity slightly further. The results suggest that cardiac afferents play the dominant role in the renal sympathoinhibition in response to volume expansion in the normal conscious rabbit.
A functional role for central glucagon-like peptide-1 receptors in lithium chloride-induced anorexia
Authors: Rinaman Linda
Published: December 2017

The present study sought to determine whether central glucagon-like peptide-1 (GLP-1)-receptor signalling contributes to the anorexigenic effects of systemically administered lithium chloride (LiCl). Male Sprague-Dawley rats with chronic intracerebroventricular (ICV) cannulas were acclimated to a feeding schedule that included daily 30-min access to palatable mash. In the first experiment, ICV infusion of a GLP-1-receptor antagonist [exendin-4-(3—39)] significantly attenuated (10 μg dose) or completely blocked (20 μg dose) the inhibition of food intake produced by subsequent ICV infusion of GLP-1-(7—36) amide (5 μg). In the second experiment, rats were infused with 0, 10, or 20 μg of the GLP-1-receptor antagonist ICV, followed by injection of 0.15 M LiCl (50 mg/kg ip) or the same volume of 0.15 M NaCl. The ability of LiCl treatment to suppress food intake was significantly attenuated in rats that were pretreated with the GLP-1-receptor antagonist. These results support the view that central mechanisms underlying LiCl-induced anorexia include a prominent role for endogenous GLP-1 neural pathways.
Circadian rhythms in the chemoreflex control of breathing
Authors: Stephenson Richard , Mohan Ravi M. , Duffin James , Jarsky Tim M.
Published: December 2017

Mechanisms underlying the circadian rhythm in lung ventilation were investigated. Ten healthy male subjects were studied for 36 h using a constant routine protocol to minimize potentially confounding variables. Laboratory light, humidity, and temperature remained constant, subjects did not sleep, and their meals and activities were held to a strict schedule. Respiratory chemoreflex responses were measured every 3 h using an iso-oxic rebreathing technique incorporating prior hyperventilation. Subjects exhibited circadian rhythms in oral temperature and respiratory chemoreflex responses, but not in metabolic rate. Basal ventilation [i.e., at subthreshold end-tidal carbon dioxide partial pressure ([Formula: see text])] did not vary with time of day, but the ventilatory response to suprathreshold[Formula: see text] exhibited a rhythm amplitude of ∼25%, mediated mainly by circadian variations in the CO2 threshold for tidal volume. We conclude that the circadian rhythm in lung ventilation is not a simple consequence of circadian variations in arousal state and metabolic rate. By raising the chemoreflex threshold, the circadian timing system may increase the propensity for respiratory instability at night.
Tissue hypoxygenation activates the adrenomedullin system in vivo
Authors: Hofbauer Karl-Heinz , Jensen Boye L. , Kurtz Armin , Sandner Peter
Published: December 2017

Our study aimed to investigate the influence of tissue hypoxygenation on the adrenomedullin (ADM) system in vivo. For this purpose, male Sprague-Dawley rats were exposed to normobaric hypoxia (8% oxygen) or to functional anemia [0.1% carbon monoxide (CO)] or to cobalt chloride (60 mg/kg) for 6 h. Messenger RNA levels for ADM and its receptor (ADM-R) were assessed in diverse organs by RNase protection assay. Additionally, ADM protein concentrations in these organs, as in plasma, were determined by a RIA. We found that ADM mRNA abundance increased in response to hypoxia and to CO inhalation up to 15-fold in all organs examined. Similarly, ADM-R mRNA abundance increased during hypoxia and CO inhalation in all organs examined with exception of the liver. The effects of hypoxia and of CO inhalation on ADM and ADM-R mRNAs were mimicked by injection of cobaltous chloride. Hypoxia also significantly increased ADM protein content in all organs, and plasma levels of ADM rose twofold in response to hypoxia and CO inhalation. These findings indicate that tissue hypoxia leads to a widespread activation of the ADM system, which comprises a parallel stimulation of ADM and ADM receptor mRNA as enhanced ADM protein synthesis and secretion. The ADM system may, therefore, play a significant role in the physiological response to tissue hypoxia. It appears that ADM and ADM-R belong to the family of classic oxygen-regulated genes, which are activated by a decrease of the pericellular oxygen tension through the same intracellular signaling cascade.
Nociceptin inhibits rat sympathetic preganglionic neurons in situ and in vitro
Authors: Lai Chih-Chia , Wu Su Ying , Chen Chiung-Tong , Dun Nae J.
Published: December 2017

In vitro and in situ experiments were conducted to evaluate the hypothesis that the nonclassical opioid peptide nociceptin acting on sympathetic preganglionic neurons (SPNs) inhibits spinal sympathetic outflow. First, whole cell patch recordings were made from antidromically identified SPNs from immature (12–16 day old) rat spinal cord slices. Nociceptin (0.1, 0.3, and 1 μM) concentration dependently suppressed the excitatory postsynaptic potentials (EPSPs) evoked by focal stimulation and hyperpolarized a population of SPNs; these effects were naloxone insensitive.l-Glutamate-induced depolarizations were not significantly changed by nociceptin. Results from this series of experiments indicate that nociceptin inhibits the activity of SPNs by either a presynaptic or postsynaptic site of action, whereby the peptide reduces, respectively, the amplitude of EPSPs or the excitability of SPNs. Second, intrathecal injection of nociceptin (3, 10, and 30 nmol) to urethan-anesthetized rats dose dependently reduced the mean arterial pressure and heart rate; these effects were not prevented by prior intravenous administration of naloxone (1 mg/kg). Physiological saline given intrathecally was without appreciable effects. These results, together with earlier observations of the detection of nociceptin-immunoreactive nerve fibers and nociceptin receptor immunoreactivity in the rat intermediolateral cell column, raise the possibility that the opioid peptide, which may be released endogenously, reduces spinal sympathetic outflow by depressing the activity of SPNs.
Macronutrient diet selection in thirteen mouse strains
Authors: Smith Brenda K. , Andrews P. Kyle , West David B.
Published: December 2017

The strain distribution for macronutrient diet selection was described in 13 mouse strains (AKR/J, NZB/B1NJ, C57BL/6J, C57BL/6ByJ, DBA/2J, SPRET/Ei, CD-1, SJL/J, SWR/J, 129/J, BALB/cByJ, CAST/Ei, and A/J) with the use of a self-selection protocol in which separate carbohydrate, fat, and protein diets were simultaneously available for 26–30 days. Relative to carbohydrate, nine strains consumed significantly more calories from the fat diet; two strains consumed more calories from carbohydrate than from fat (BALB/cByJ, CAST/Ei). Diet selection by SWR/J mice was variable over time, resulting in a lack of preference. One strain (A/J) failed to adapt to the diet paradigm due to inadequate protein intake. Comparisons of proportional fat intake across strains revealed that fat selection/consumption ranged from 26 to 83% of total energy. AKR/J, NZB/B1NJ, and C67BL/6J mice self-selected the highest proportion of dietary fat, whereas the CAST/Ei and BALB/cByJ strains chose the lowest. Finally, epididymal fat depot weight was correlated with fat consumption. There were significant positive correlations in AKR/J and C57BL/6J mice, which are highly sensitive to dietary obesity. However, absolute fat intake was inversely correlated with epididymal fat in two of the lean strains: SWR/J and CAST/Ei. We hypothesize that the SWR/J and CAST/Ei strains are highly sensitive to a negative feedback signal generated by increasing body fat, but the AKR/J and C67BL/6J mice are not. The variation in dietary fat selection across inbred strains provides a tool for dissecting the complex genetics of this trait.
Activation of renal mechanosensitive neurons involves bradykinin, protein kinase C, PGE2, and substance P
Authors: Kopp Ulla C. , Farley Donna M. , Cicha Michael Z. , Smith Lori A.
Published: December 2017

Increased renal pelvic pressure or bradykinin increases afferent renal nerve activity (ARNA) via PGE2-induced release of substance P. Protein kinase C (PKC) activation increases ARNA, and PKC inhibition blocks the ARNA response to bradykinin. We now examined whether bradykinin mediates the ARNA response to increased renal pelvic pressure by activating PKC. In anesthetized rats, the ARNA responses to increased renal pelvic pressure were blocked by renal pelvic perfusion with the bradykinin B2-receptor antagonist HOE 140 and the PKC inhibitor calphostin C by 76 ± 8% ( P < 0.02) and 81 ± 5% ( P < 0.01), respectively. Renal pelvic perfusion with 4β-phorbol 12,13-dibutyrate (PDBu) to activate PKC increased ARNA 27 ± 4% and renal pelvic release of PGE2 from 500 ± 59 to 1,113 ± 183 pg/min and substance P from 10 ± 2 to 30 ± 2 pg/min (all P < 0.01). Indomethacin abolished the increases in substance P release and ARNA. The PDBu-mediated increase in ARNA was also abolished by the substance P-receptor antagonist RP 67580. We conclude that bradykinin contributes to the activation of renal pelvic mechanosensitive neurons by activating PKC. PKC increases ARNA via a PGE2-induced release of substance P.
Carotid and cardiopulmonary chemoreceptor activity increases hippocampal theta rhythm in conscious rabbits
Authors: Yu Ying-Hui , Blessing W. W.
Published: December 2017

We have examined whether activation of carotid artery chemoreceptors causes alerting in conscious rabbits. Injection of phenylbiguanide (a 5-hydroxytryptamine3-receptor agonist) into the common carotid artery of conscious rabbits increased the proportion of theta rhythm in the hippocampal EEG, commencing in the first 5-s epoch after the injection. Intravenous injection of phenylbiguanide also increased the proportion of theta rhythm in the hippocampal electroencephalogram (EEG), but the onset of the change was not until the second 5-s epoch following injection. Injection of Ringer solution, either into the common carotid artery or into the marginal ear vein, did not affect the hippocampal EEG. Results suggest that phenylbiguanide-mediated activation of carotid and cardiopulmonary chemoreceptor afferents alerts the animal, as assessed by induction of theta rhythm in the hippocampal EEG. This alerting response presumably reflects the action of neural inputs that enter the brain with the carotid sinus nerve at the level of the medulla oblongata.
Rhythms in Fos expression in brain areas related to the sleep-wake cycle in the diurnal Arvicanthis niloticus
Authors: Novak Colleen M. , Smale Laura , Nunez Antonio A.
Published: December 2017

Most mammals show daily rhythms in sleep and wakefulness controlled by the primary circadian pacemaker, the suprachiasmatic nucleus (SCN). Regardless of whether a species is diurnal or nocturnal, neural activity in the SCN and expression of the immediate-early gene product Fos increases during the light phase of the cycle. This study investigated daily patterns of Fos expression in brain areas outside the SCN in the diurnal rodent Arvicanthis niloticus. We specifically focused on regions related to sleep and arousal in animals kept on a 12:12-h light-dark cycle and killed at 1 and 5 h after both lights-on and lights-off. The ventrolateral preoptic area (VLPO), which contained cells immunopositive for galanin, showed a rhythm in Fos expression with a peak at zeitgeber time (ZT) 17 (with lights-on at ZT 0). Fos expression in the paraventricular thalamic nucleus (PVT) increased during the morning (ZT 1) but not the evening activity peak of these animals. No rhythm in Fos expression was found in the centromedial thalamic nucleus (CMT), but Fos expression in the CMT and PVT was positively correlated. A rhythm in Fos expression in the ventral tuberomammillary nucleus (VTM) was 180° out of phase with the rhythm in the VLPO. Furthermore, Fos production in histamine-immunoreactive neurons of the VTM cells increased at the light-dark transitions when A. niloticus show peaks of activity. The difference in the timing of the sleep-wake cycle in diurnal and nocturnal mammals may be due to changes in the daily pattern of activity in brain regions important in sleep and wakefulness such as the VLPO and the VTM.
Attenuation of circadian rhythms of food intake and respiration in aging diabetes-prone BHE/Cdb rats
Authors: Mathews Clayton E. , Wickwire Kathie , Flatt Wiliam P. , Berdanier Carolyn D.
Published: December 2017

The hypothesis that BHE/Cdb rats with mutations in their mitochondrial genome might accommodate this mutation by changing their food intake patterns was tested. Four experiments were conducted. Experiments 1 and 2examined food intake patterns of BHE/Cdb rats fed a stock diet or BHE/Cdb and Sprague-Dawley rats fed a high-fat diet from weaning. Experiment 3 examined the daily rhythms of respiration and heat production in these rats at 200 days of age. Experiment 4 examined the effects of diet composition on these measurements at 50-day intervals. The Sprague-Dawley rats, regardless of diet, had the typical day-night rhythms of feeding and respiration. In contrast, the BHE/Cdb rats fed the high-fat diet showed normal rhythms initially, but with age, these rhythms were attenuated. The changes in rhythms preceded the development of glucose intolerance.
Exogenous and endogenous corticosteroids modulate blood-brain barrier development in the ovine fetus
Authors: Stonestreet Barbara S. , Sadowska Grazyna B. , McKnight Amanda J. , Patlak Clifford , Petersson Katherine H.
Published: December 2017

We previously reported decreases in blood-brain barrier permeability in the ovine fetus at 80% of gestation after antenatal corticosteroids and shown that permeability is not reduced in newborn lambs after postnatal corticosteroids. We now test the hypotheses that exogenous antenatal corticosteroids decrease blood-brain barrier permeability at 60% but not 90% of gestation in ovine fetuses and that endogenous increases in plasma cortisol concentrations are associated with ontogenic decreases in barrier permeability during gestation. Chronically instrumented ovine fetuses were studied 12 h after the last of four 6-mg dexamethasone or placebo injections were given 12 h apart over 48 h to ewes. Fetuses at 80% of gestation from placebo-treated ewes studied under the same protocol were also included. Blood-brain barrier function was quantified with the blood-to-brain transfer constant ( K i) to α-aminoisobutyric acid. K i values were lower in cerebral cortex, caudate nucleus, hippocampus, superior colliculus, thalamus, medulla, and cervical spinal cord in fetuses of dexamethasone- than placebo-treated ewes at 60% but not 90% of gestation. Regional brain K i values demonstrated inverse correlations with increases in gestation and plasma cortisol concentrations in most brain regions. We conclude that maternal treatment with exogenous corticosteroids was associated with decreases in blood-brain barrier permeability at 60% but not 90% of gestation and that increases in gestation and endogenous cortisol concentrations were associated with ontogenic decreases in barrier permeability during fetal development.
Role of renin-angiotensin system in hypotension-evoked thirst: studies with hydralazine
Authors: Stocker Sean D. , Sved Alan F. , Stricker Edward M.
Published: December 2017

Injection of rats either with diazoxide (25 mg/kg iv), isoproterenol (0.33 mg/kg sc), or hydralazine (HDZ) (10 mg/kg ip) decreased arterial blood pressure from ∼120 to 70–80 mmHg and stimulated renin secretion. However, diazoxide and isoproterenol treatments each stimulated water ingestion, whereas HDZ treatment did not. HDZ treatment did not reduce water intake evoked by systemic injection of hypertonic saline or 20% polyethylene glycol solution or by 24-h water deprivation, suggesting that HDZ treatment did not interfere with drinking behavior. In contrast, HDZ treatment markedly reduced water intake evoked by injection of diazoxide or isoproterenol or by intravenous infusion of renin. Furthermore, a highly significant correlation was observed when plasma ANG II levels were plotted as a function of plasma renin activity after intravenous infusion of renin and after diazoxide and isoproterenol treatments. However, values obtained after HDZ treatment alone or in combination with intravenous infusion of renin did not fall near the 99% confidence interval of the regression line, suggesting that HDZ treatment blocks ANG II production and/or promotes its clearance. Thus rats apparently do not increase water intake after HDZ treatment, because this drug interferes with the renin-angiotensin system. These results provide further evidence that arterial hypotension evokes thirst in rats predominantly by activation of the renin-angiotensin system.
Sympathetic reflexes after depletion of bulbospinal catecholaminergic neurons with anti-DβH-saporin
Authors: Schreihofer Ann M. , Guyenet Patrice G.
Published: December 2017

We examined the effects of destroying bulbospinal catecholaminergic neurons with the immunotoxin anti-dopamine β-hydroxylase-saporin (anti-DβH-Sap) on splanchnic nerve activity (SNA) and selected sympathetic reflexes in rats. Anti-DβH-Sap was administered into the thoracic spinal cord with the retrograde tracer fast blue. After 3–5 wk, anti-DβH-Sap eliminated most bulbospinal C1 (>74%), C3 (∼84%), A5 (∼98%), and A6 cells. Noncatecholaminergic bulbospinal neurons of the rostral ventrolateral medulla and serotonergic neurons were spared. Under chloralose anesthesia, mean arterial pressure and heart rate of anti-DβH-Sap-treated rats (3–5 wk) were normal. Resting SNA was not detectably altered, but the baroreflex range and gain were reduced ∼40% ( P < 0.05). Phenyl biguanide-induced decreases in mean arterial pressure, heart rate, and SNA were unchanged by anti-DβH-Sap, but the sympathoexcitatory response to intravenous cyanide was virtually abolished ( P < 0.05). Rats that received spinal injections of saporin conjugated to an anti-mouse IgG had intact bulbospinal C1 and A5 cells and normal physiological responses. These data suggest that C1 and A5 neurons contribute modestly to resting SNA and cardiopulmonary reflexes. However, bulbospinal catecholaminergic neurons appear to play a prominent sympathoexcitatory role during stimulation of chemoreceptors.
Effect of luminal angiotensin II and ANP on early and late cortical distal tubule HCO3- reabsorption
Authors: Barreto-Chaves M. L. , Mello-Aires M.
Published: December 2017

Bicarbonate reabsorption was evaluated by stationary microperfusion “in vivo“ early distal (ED) and late distal (LD) segments of at kidney. Intratubular pH was recorded by double-barreled of H+ exchange resin/reference (1 M KCl) microelectrodes for the determination of HCO3- reabsorption. In the presence of angiotensin II (ANG II) (10(-12) M), a significant increase in HCO3- reabsorption was observed both in ED (from 0.930 +/- 0.060 to 2.64 +/- 0.210 nmol.cm-2.s-1 in luminally perfused tubules and from 0.850 +/- 0.040 to 2.03 +/- 0.210 nmol.cm-2.s-1 during capillary perfusion) and LD segments from 0.310 +/- 0.130 to 2.16 +/- 0.151 nmol.cm-2.s-1 during luminal perfusion and from 0.530 +/- 0.031 to 2.16 +/- 0.211 nmol.cm-2.s-1 with capillary perfusion). The addition of the AT1-receptor antagonist losartan (10(-6) M) to luminal perfusion blocked luminal ANG II-mediated stimulation in ED and LD segments. 5-(N,N-hexamethylene)amiloride (10(-4) M) added to luminal perfusion inhibited luminal ANG II-mediated stimulation in ED (by 81%) and LD (by 54%) segments. The addition of bafilomycin A1 (2 x 10(-7) M) to luminal perfusion does not affect luminal ANG II-mediated stimulation in ED segments but reduces it in LD segments (by 33%). During the addition of atrial natriuretic peptide (ANP) (10(-6) M) or ANG II plus ANP in both segments, no significant differences in HCO3- reabsorption were observed. Our results indicate that luminal ANG II acts to stimulate Na+/H+ exchange in ED and LD segments via activation of AT1 receptors, as well as the vacuolar H(+)-adenosinetriphosphatase in LD segments. ANP does not affect HCO3- reabsorption in either ED or LD segments and does not impair the stimulation caused by ANG II.
“Alveolar plateau” of the single breath nitrogen elimination curve in normal subjects
Authors: Kjellmer Ingemar , Sandqvist Lars , Berglund Erik
Published: December 2017

The single breath N2 elimination test, as standardized by Comroe and Fowler, has been used in normal subjects. The N2 difference, i.e. the difference in N2 concentration between Ve = 1250 and Ve = 750 ml, showed a tendency to increase with increasing volumes of inspired O2 and with increasing inspiratory flow rates. It decreased with increasing breath-holding time and was not consistently influenced by expiratory flow rate. The findings are compared with those of Fowler and of Shephard on normal subjects; different results were obtained, largely depending on different analytical procedures. These factors must be considered when evaluating results in patients.

Submitted on July 21, 1958
Influence of abdominal muscles, mesenteric viscera and liver on respiratory mechanics
Authors: Brody Alfred W. , Connolly John J. , Wander Harry J.
Published: December 2017

In a group of 13 supine, anesthetized cats initial measurement was made of respiratory elastance, total resistance by sinusoidal pressure, total resistance, k1 and k2 and their ratio of change from breath to breath, the natural frequency, damping factor and mass factor or inertance, and the functional residual capacity (FRC) and tissue resistance. Comparison was then made with the value obtained by remeasurement in the same cat after a) control operation of mid-line abdominal incision; b) incisions eliminating the effects of the abdominal muscles (mid-line vertical plus transverse incision extended to back); c) evisceration of gastrointestinal tract and spleen and d) evisceration plus hepatectomy. The abdominal response was found to be mainly a surface wave response (at a speed of about 150 cm/sec.) above the natural frequency. The abdominal muscles impose a steady force, more like a weight than a spring, which decreases the FRC. The liver contributes significantly to the mass factor and natural frequency, but the viscera do not. About half the tissue resistance consists of a resistance within the abdomen to respiratory movements; since nearly half the total resistance is tissue resistance, this is nearly one fourth the total resistance to respiration.

Submitted on June 2, 1958
Fluid volume redistribution and thoracic volume changes during recumbency
Authors: Tenney S. M.
Published: December 2017

Continuous measurements of change in center of gravity, thoracic and abdominal girths and extremity volume over a 30-minute period of recumbency were recorded in 20 normal young adults. Vital capacity, expiratory reserve volume and residual volumes were recorded at the beginning and end of the period. No significant differences between the initial and final vital capacities or residual volumes were observed. Expiratory reserve volume decreased and correlated positively with the measured change in torque. Abdominal and thoracic end expiratory circumferences both increased. Four young adults, normal except for congenital or traumatic absence of the lower extremities, were examined in the same manner. In these subjects the change in center of gravity was minimal and the thoracic circumference did not increase. The pattern of lung volume changes during recumbency was similar to normal subjects. It is concluded that during recumbency the lower extremities contribute blood to the thoracic pool and this is manifested as an increase in thoracic girth, but without decrease in total lung volume. The diaphragm assumes a more expiratory position and is partially responsible for the change in expiratory reserve volume.

Submitted on August 4, 1958
Relationship of potassium and calcium to hypothermic ventricular fibrillation
Authors: Beavers William R. , Covino Benjamin G.
Published: December 2017

Pentobarbital-anesthetized dogs, cooled in ice water to terminus, were found to have a 96% incidence of ventricular fibrillation. Plasma potassium levels were uniformly depressed at low body temperatures. Treatment with Intravenous potassium chloride, 150– 250 mg/kg, reduced the frequency of fibrillation to 57%. Administration of EDTA (ethylene diamine tetracetic acid), 75 mg/kg in divided doses, lowered serum calcium levels but affected the incidence of fibrillation only slightly. Combined therapy with potassium chloride and EDTA reduced the incidence of ventricular fibrillation to 50%. These results are interpreted as indicating that ionic imbalance observed with hypothermia produces a marked arrhythmic tendency and that proper alteration of plasma potassium levels reduces the danger of fibrillation.

Submitted on July 28, 1958
Regional inhomogeneity of alveolar air and R.Q. differences in the lungs of the normal dog
Authors: Bechtel A. A.
Published: December 2017

Regional inhomogeneity of alveolar air was studied by simultaneous sampling through catheters in primary or secondary bronchi, at the end of normal expiration in dogs under sodium pentobarbital anesthesia. With dogs lying on the back, the right lung usually had the lower Pco2, higher Po2 and higher R. P( t) < .001 for each difference. In the side-lying position the ‘down’ lung usually had the higher Po2 and R unless the catheters were placed so deep as to differentially obstruct the airway in that lung.

Submitted on July 3, 1958
Quantitative studies of perception of thermal stimuli in the normal and neurogenic urinary bladder
Authors: McDonald Donald F. , Murphy Gerald P.
Published: December 2017

Quantitative measurements of the ability of human beings to perceive temperature changes in the urinary bladder were made using copper-constantan thermocouples connected to a continuous recording electronic potentiometer. Ten different thermal changes were induced by irrigation of the bladder with cold or warm saline solution. Each stimulus was presented to each subject 10 times, according to a table of random numbers. The subjects were asked to indicate whether they felt warmer or colder. The stimulus was maintained for less than 3 seconds. In 40 normal volunteers, the mean warm response was 93℉. The mean cool response was 87.5℉. The neutrality point where the two curves intersected was 89.4℉. Statistical evaluation established the validity of the differences. The thermal sensation of seven patients with varying levels of spinal cord trauma seemed to indicate that the afferent pathway for thermal bladder sensation involved S2,3,4cord segments.

Submitted on December 5, 1958
Circulatory adjustments of voluntary muscle in anemia
Authors: Verel D. , Duff R. S.
Published: December 2017

Simultaneous measurements of the blood flow through the human forearm and of the arteriovenous oxygen difference of forearm blood have shown that in moderate anemia the need for oxygen was met by an increase in the arteriovenous oxygen difference without increase in blood flow. When the hemoglobin fell below 4 gm.% the blood flow rose. In subjects in whom the blood flow had increased, the venous oxygen saturation was below 15%. Cardiac output has been shown to increase when the hemoglobin falls below 8 gm.%. It is concluded that the initial increase in heart output is not due to ischemia of voluntary muscle but is required for maintaining the metabolism of the brain and the heart itself.

Submitted on July 3, 1958
Diminished blood ATP levels induced in the chick by dietary aluminum hydroxide gel
Authors: Bishop C. , Williams C. , Rodbard S.
Published: December 2017

When newly hatched chicks are placed on a diet containing a reactive aluminum hydroxide gel, the fatal syndrome of progressive leg and wing weakness which they develop is accompanied by a reduction in the quantity of adenosine triphosphate (ATP) in the blood. The intramuscular injection of an emulsion of inorganic phosphate tends to prevent this change. It is suggested that these chicks fed alumina gel are deficient in inorganic phosphate and that their reduced ability to maintain blood ATP levels is indicative of reduced phosphorylating ability elsewhere in the body.

Submitted on November 13, 1958
Diffusion of water vapor through human skin in hot environment and with application of atropine
Authors: Buettner Konrad J. K. , Holmes Frederick F.
Published: December 2017

At room temperatures between 20° and 40°C, vapor transfer through skin of human forearm was tested with four small heated bottles containing air of humidities ranging from 2 to 100% relative humidity. Exposure times ranging from 30 to 120 minutes had no influence on results. Water loss or gain of skin were observed for the different bottles. At very high humidities, liquid water deposit on the skin was measured by weighing a blotter. Skin vapor loss decreases systematically when bottle moisture increases. This increase is enhanced at room temperatures above 24℃, where total loss into a dry bottle increases more than fivefold. This increase seems only partially caused by sweat and partially by a decrease of the skin diffusion resistance. Tourniquet and locally applied atropine did not affect vapor transfer in a cool room. In a hot room, the tourniquet lowered the vapor loss by only 20%, whereas atropine drastically curtailed vapor loss.

Submitted on August 25, 1958
Effect of posture on pulmonary dead space in man
Authors: Riley R. L. , Permutt S. , Said S. , Godfrey M. , Cheng T. O. , Howell J. B. L. , Shepard R. H.
Published: December 2017

Physiologic dead space was determined in the supine and upright postures by simultaneous sampling and subsequent analysis of arterial blood and expired gas for Pco2. In seven normal men there was invariably a higher dead space in the upright than in the supine position. The difference averaged 83 ml and was statistically significant (S.E. 25 ml and P < 0.01). The ratio of dead space to tidal volume also invariably increased on assuming the upright posture. Evidence is presented for believing that most of the change in physiologic dead space resulted from a change in alveolar dead space. Estimated changes in the ratio of alveolar dead space to alveolar tidal volume suggest that approximately one seventh of the total number of alveoli became nonperfused on changing from the supine to the erect posture. These findings are consistent with bronchospirometric and hemodynamic evidence that the apex of the lung is virtually nonperfused in the resting human subject in the upright posture.

Submitted on November 12, 1958
Comparison of vital capacity and maximum breathing capacity of athletes and nonathletes
Authors: Stuart Douglas G. , Collings W. D.
Published: December 2017

The vital capacity (VC), maximum breathing capacity (MBC) and MBC/VC measurements of 20 athletes and 20 nonathletes were compared. The mean VC score of the athletes was significantly higher than the mean nonathlete VC, but insignificant differences existed between the two groups in MBC and MBC/VC. It is suggested that the difference in VC is due to increased development of respiratory musculature incidental to regular physical training. This increase is not reflected in the MBC since this measurement would appear to be more concerned with the presence or absence of obstructive ventilatory defects that are unaffected by physical training. Results are compared with data from the literature.

Submitted on December 5, 1959
Ventilatory response to fixed acid evaluated by ‘iso-Pco2’ technique
Authors: Domizi Dario B. , Perkins John F. , Byrne Joan S.
Published: December 2017

In order to avoid changes in a second stimulus to ventilation, i.e. carbon dioxide, while measuring the response to fixed acid, a technique was utilized whereby alveolar carbon dioxide tension (PaCOCO2) could be held constant. This technique includes continuous recording of PaCOCO2 with an infrared type analyzer and addition of sufficient CO2 to the inspired air to keep PaCOCO2 at its control value (near 40 mm Hg). The response of anesthetized dogs to infusion of 0.5 m HCl was measured when the PaCOCO2 was held at the control value and also at various other levels. Other experiments measured the effect of CO2 when it was not allowed to change arterial hydrogen ion concentration [H+]. It was found that both these substances are potent respiratory stimuli and that their effects may be considered essentially separate and additive, as suggested by Gray. The experiments also demonstrated a slightly increased sensitivity to CO2 at increased arterial [H+], but this effect was not found necessary to explain the response to acid. Responses to successive small increments in PaCOCO2 failed to reveal any ‘threshold,’ even with CO2 tensions as low as 15 mm during acidosis.

Submitted on December 29, 1958
Breath holding after breathing of oxygen
Authors: Klocke F. J. , Rahn H.
Published: December 2017

Following normal breathing of O2 seven untrained subjects held their breath beginning with a maximal inspiration. Breath-holding times ranged from 3.1 to 8.5 minutes and ‘breaking-point’ alveolar CO2 tensions from 51 to 91 mm Hg. Under these conditions, the maximum breath-holding time in minutes ( x) can be related to the rise in alveolar CO2 tension in mm Hg ( y), according to the equation x = 0.13 y + 1.4. After hyperventilation on O2, the breath-holding times were noticeably extended ranging from 6 to 14 minutes, but the breaking-point alveolar CO2 tensions did not exceed those noted above. In all cases, the measured changes in lung volume can be explained by the uptake of oxygen alone since the amount of CO2 is essentially unaltered during apnea. The decreases in lung volume observed are related to the total breath-holding time, about 13 minutes being required for a change in lung volume equal to the vital capacity. Three subjects were able to absorb their entire vital capacity volume during breath holding since no volume could be expired at the breaking point.

Submitted on April 8, 1959
Response of Negro and white males to cold
Authors: Iampietro P. F. , Goldman R. F. , Buskirk E. R. , Bass David E.
Published: December 2017

Heat production and body temperatures were measured in matched groups of U.S. Negro and white soldiers during whole body cooling and finger temperatures were measured when only the digits were cooled. Whole body cooling was accomplished by having the subjects, clad only in shorts, sit for 2 hours in a chamber at 50℉ with a 5-mph wind. Digital cooling was accomplished by having the subjects immerse the fingers in a water bath at 32℉ for 45 minutes. During whole body cooling there were no group differences with respect to the following: heat production, skin and rectal temperatures. During digital cooling white subjects had higher finger temperatures and the ‘hunting’ reaction was more pronounced than for Negroes. In addition, the white subjects required a shorter period for the onset of the first ‘rewarming’ of the fingers. The implications of these findings with reference to the reported higher incidence of cold injury among Negro soldiers are discussed.

Submitted on February 19, 1959
Capillary resistance and blood pressure changes associated with pain due to local cooling: cold pressor test
Authors: McMurray Gordon A. , Jaques Louis B.
Published: December 2017

Measurements of capillary resistance and blood pressure were made before and after immersion of the right hand in ice water for 5 minutes. The capillary resistance rose sharply immediately after stress and remained elevated for over 3 hours, returning to normal in 21 hours, while the blood pressure response reached its peak in 90 seconds. A significant negative correlation was found between the maximum changes in capillary resistance and blood pressure.

Submitted on March 5, 1959
Requirements of sodium chloride during summer in the tropics
Authors: Malhotra M. S. , Sharma B. K. , Sivaraman R.
Published: December 2017

Data are presented on salt requirements in the tropics, based on observations on 24 acclimatized Indian subjects given diets containing 16.2, 11.2, 8.7, 6.2 and 3.1 gm of salt per day. Adequacy of salt diet was tested from the chloride excretion in urine and from the changes observed in thiocyanate space and plasma chloride concentration at the start and after the subjects had been on the restricted salt diet for a week. Sweat and chloride losses at different environmental temperatures were studied. The salt requirement of subjects walking for 2 hours in the sun at a speed of about 3.5 mph was found to be about 6.2 gm/day when the mean maximum environmental temperature was 100.7℉ D.B. The requirement was found to increase by 0.063 gm/℉ rise in D.B. temperature for 2 hours' exercise.

Submitted on September 12, 1958
Acetate metabolism in bovine ketosis
Authors: Kronfeld D. S. , Kleiber Max , Lucas J. M.
Published: December 2017

The metabolism of intravenously injected acetate–1–C14 was compared in normal and ketotic cows. The mean standardized specific activity of milk citrate, casein, lactose, plasma glucose, respired carbon dioxide and urine acetone was greater in the ketotic than in the normal cows, while that of milk fat was markedly decreased. The total–C14 recovered in the milk fat within 48 hours was about 14% of the injected dose in the normal cows, but only about 3% in the ketotic cows. These results suggest that the proportion of acetate metabolized via the tricarboxylic acid cycle is increased, while milk fat synthesis from acetate is impaired during bovine ketosis.

Submitted on December 15, 1958
Estimation of energy expenditure from pulmonary ventilation
Authors: Ford Amasa B. , Hellerstein Herman K.
Published: December 2017

A method for estimating energy expenditure from pulmonary ventilation is presented and tested by analysis of 272 observations made under field conditions on 52 factory and steel mill workers. Energy expenditure (Calories/min.) equals 0.173 times ventilation (liters/min., BTPS), minus 0.52, with a standard error of estimate of 0.42 Calories per minute. The use of individual regression lines will permit more accurate estimation of energy expenditure when multiple observations are to be made on one subject.

Submitted on June 10, 1959
Effect of lipemia on arterial oxygen at high altitude
Authors: Stutman Leonard J. , Kriewaldt Frank H. , Doerr Vern , George Marilyn
Published: December 2017

Some of the effects of acute fat loading on arterial O2 at high altitude are described. Five dogs were taken to 12,000 feet in an altitude chamber and given fat infusions (1 gm/kg). There was a 10% drop in the arterial O2 content and a similar drop in the O2 capacity. One of the dogs had a surgically induced intra-atrial septal defect and died of fat emboli. Three dogs serving as controls at ground level had a 4% drop in arterial O2 content after fat infusions. A practical method for screening poor human risks among flying personnel, employing a fat tolerance test, is discussed. The drop in the O2 content and capacity of canine blood after fat infusions at 12,000 feet is at least twice that at ground level.

Submitted on July 13, 1959
Influence of acute pulmonary vascular congestion on recoiling force of excised cats' lung
Authors: Frank N. R.
Published: December 2017

The effects of acute reversible pulmonary vascular congestion on the elastic behavior of excised cats' lungs were studied in 10 preparations. Measurements were made of changes in airway pressure at constantly held lung volumes over a wide range of deflation. To achieve vascular congestion left atrial pressure was raised to 20 and 30 cm H2O. Two effects were noted; one was that the slope of the volume-pressure relations of the lungs was slightly reduced at all levels of deflation, the other, the effect of vascular congestion on the recoiling force of the lungs was a function of the volume of the lungs at which congestion was induced. At large volumes (airway pressures of 5 cm H2O or more) recoiling force was increased; at intermediate volumes (airway pressures of 2.5 and 3 cm H2O) the change was negligible and, at smaller volumes, it was reduced in a manner consistent with the early work of von Basch. The findings suggest that there is a volume of the lungs, or perhaps a narrow range of volume, at which the lungs and blood vessels exert least mechanical stress on each other. This volume is believed to lie close to that in which tidal breathing occurs.

Note:

(With the Technical Assistance of Elcanor Gotz)

Submitted on April 17, 1959
Effect of transverse acceleration on pulmonary function
Authors: Cherniack Neil S. , Hyde Alvin S. , Zechman F. W.
Published: December 2017

Since difficulty with respiration limits tolerance to transverse acceleration, the effect of this acceleration on different respiratory factors was tested in 15 subjects. Minute volume, respiratory rate, tidal volume, maximum breathing capacity, 0.5-second timed vital capacity and total vital capacity were measured at 3 and 5 g with the subject's trunk perpendicular to the centrifugal force and legs and knees flexed at 90 degrees. Vital capacity was reduced significantly at 3 and 5 g. Maximum breathing capacity was significantly reduced at 5 g. One-half-second timed vital capacity represented an increasing fraction of total vital capacity as acceleration increased. Minute volume and respiratory rate also increased significantly at 5 g while tidal volume was essentially unchanged. Results are obtained which indicate that the nature of the predominant respiratory defect during forward acceleration is restrictive. Of the respiratory parameters measured, vital capacity showed the greatest decrement.

Submitted on April 17, 1959