bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary vasodilator responses to adrenomedullin are reduced by NOS inhibitors in rats but not in cats
Authors: Nossaman B. D. , Feng C. J. , Kaye A. D. , DeWitt B. , Coy D. H. , Murphy W. A. , Kadowitz P. J.
Published: December 2017

Responses to and the mechanism of action of adrenomedullin (ADM), the carboxy-terminal fragments of ADM, and calcitonin gene-related peptide (CGRP), a structurally related peptide, were investigated in the pulmonary vascular bed of the rat. Under conditions of elevated tone and controlled pulmonary blood flow in the isolated blood-perfused rat lung, injections of ADM, the 15-52 amino acid carboxy-terminal ADM analogue (ADM15-52), and CGRP caused dose-related decreases in pulmonary arterial perfusion pressure. In contrast, the carboxy-terminal 22-52 and 40-52 amino acid fragments had no consistent vasodilator activity. After administration of the nitric oxide synthase inhibitors, N omega-nitro-L-arginine benzyl ester or N omega-nitro-L-arginine methyl ester (L-NAME), pulmonary vasodilator responses to ADM, to ADM15-52, to CGRP, to acetylcholine, and to bradykinin were significantly decreased in the rat, whereas vasodilator responses to isoproterenol and nitroglycerin were not changed. However, in the pulmonary vascular bed of the cat, L-NAME had no significant effect on vasodilator responses to ADM in doses that attenuated vasodilator responses to acetylcholine and bradykinin. L-NAME had no effect on responses to isoproterenol or nitric oxide. When the relative vasodilator activity of the active peptides was compared, ADM15-52 was approximately three-fold less potent than ADM, and ADM was threefold less potent than CGRP in decreasing pulmonary vascular resistance in the rat lung. When vasodilator responses were compared in the rat and cat, ADM was threefold more potent in decreasing pulmonary vascular vascular resistance in the cat than in the rat, and vasodilator responses to ADM were independent of the intervention used to raise tone in the rat. The present data demonstrate that ADM and ADM15-52 have significant vasodilator activity in the pulmonary vascular bed of the rat, and that responses to ADM, ADM15-52, and CGRP are dependent on the release of nitric oxide in the rat. The present results indicate that pulmonary vasodilator responses to ADM are not dependent on the release of nitric oxide in the cat and suggest that responses to the peptide are mediated by different mechanisms in the pulmonary vascular bed of the rat and cat.
Adenine nucleotides via activation of ATP-sensitive K+ channels modulate hypoxic response in rat pulmonary artery
Authors: Shigemori K. , Ishizaki T. , Matsukawa S. , Sakai A. , Nakai T. , Miyabo S.
Published: December 2017

We examined the role of ATP-sensitive K+ channels in hypoxic pulmonary vasoconstriction, using isolated rat pulmonary arterial rings. Isolated rat pulmonary arterial rings displayed a rapid contraction followed by relaxation under hypoxic conditions. The ATP-sensitive K+ channel blocker glibenclamide (concentration > 1 microM) or a hyperglycemic buffer (15 mM glucose) attenuated the hypoxic relaxation in a dose-dependent manner but did not affect the hypoxia-induced contraction. To examine the relationship between hypoxia, energy, and redox state, intracellular levels of adenine nucleotides and pyridine coenzymes were determined by high-performance liquid chromatography in freeze-dried isolated rat pulmonary arteries at three time points (0, 4, and 10 min) before and during hypoxia. Hypoxia time dependently decreased the ATP content and the ATP-to-ADP ratio and increased the ADP and the AMP content in association with a rapid increase in the NADH and the NADH-to-NAD+ ratio. Hyperglycemic buffer (15 mM glucose) suppressed the hypoxia-induced changes of the adenine nucleotides (the decrease of the ATP content and the ATP-to-ADP ratio) but did not affect the hypoxia-induced changes of the NADH and the NADH-to-NAD+ ratio. Hypoxia did not affect the NADP+ or the NADPH content of pulmonary arteries. These findings indicate that an ATP-sensitive K+ channel regulates the tone of rat pulmonary arteries. Furthermore, an imbalance of the energy state may be involved in ATP-sensitive K+ channel activation during hypoxic vasorelaxation.
Capacitative Ca2+entry and tyrosine kinase activation in canine pulmonary arterial smooth muscle cells
Authors: Doi Shouzaburoh , Damron Derek S. , Horibe Mayumi , Murray Paul A.
Published: December 2017

We investigated the role of capacitative Ca2+entry and tyrosine kinase activation in mediating phenylephrine (PE)-induced oscillations in intracellular free Ca2+concentration ([Ca2+]i) in canine pulmonary arterial smooth muscle cells (PASMCs). [Ca2+]iwas measured as the 340- to 380-nm ratio in individual fura 2-loaded PASMCs. Resting [Ca2+]iwas 96 ± 4 nmol/l. PE (10 μmol/l) stimulated oscillations in [Ca2+]i, with a peak amplitude of 437 ± 22 nmol/l and a frequency of 1.01 ± 0.12/min. Thapsigargin (1 μmol/l) was used to deplete sarcoplasmic reticulum (SR) Ca2+after extracellular Ca2+was removed. Under these conditions, a nifedipine-insensitive, sustained increase in [Ca2+]i(140 ± 7% of control value) was observed when the extracellular Ca2+concentration was restored; i.e., capacitative Ca2+entry was demonstrated. Capacitative Ca2+entry also refilled SR Ca2+stores. Capacitative Ca2+entry was attenuated (32 ± 3% of control value) by 50 μmol/l of SKF-96365 (a nonselective Ca2+-channel inhibitor). Tyrosine kinase inhibition with tyrphostin 23 (100 μmol/l) and genistein (100 μmol/l) also inhibited capacitative Ca2+entry to 63 ± 12 and 85 ± 4% of control values, respectively. SKF-96365 (30 μmol/l) attenuated both the amplitude (15 ± 7% of control value) and frequency (50 ± 21% of control value) of PE-induced Ca2+oscillations. SKF-96365 (50 μmol/l) abolished the oscillations. Tyrphostin 23 (100 μmol/l) also inhibited the amplitude (17 ± 7% of control value) and frequency (45 ± 9% of control value) of the oscillations. Genistein (30 μmol/l) had similar effects. Both SKF-96365 and tyrphostin 23 attenuated PE-induced contraction in isolated pulmonary arterial rings. These results demonstrate that capacitative Ca2+entry is present and capable of refilling SR Ca2+stores in canine PASMCs and may be involved in regulating PE-induced Ca2+oscillations. A tyrosine kinase is involved in the signal transduction pathway for α1-adrenoreceptor activation in PASMCs.
Vascular expression of the αvβ3-integrin in lung and other organs
Authors: Singh Baljit , Fu Chenzhong , Bhattacharya Jahar
Published: December 2017

The expression of the αvβ3-integrin in nonproliferating vascular beds remains unclear. To determine possible organ-specific differences, we compared αvβ3-integrin expression in the lung and other organs. Paraffin-embedded tissue sections of lung, liver, brain, muscle and skin obtained from rats were processed for immunohistochemistry with a monoclonal (LM609) and a polyclonal antibody (AB1903) against the αvβ3-integrin. Immunogold electron microscopy was used to localize αvβ3-integrin in rat lung microvasculature. With the use of custom-designed primers, lung sections were subjected to in situ PCR in a thermal cycler to amplify αvor β3mRNA. To confirm specific amplification, PCR products were further hybridized in situ with an αvor β3cDNA probe. In the lung, the αvβ3-integrin protein as well as αvand β3mRNAs was extensively evident in the endothelium of extra-alveolar and alveolar microvessels, in vascular smooth muscle, and in large bronchial epithelium but not in the epithelium of alveolar ducts or alveoli. Ultrastructural immunogold labeling showed the presence of the integrin on the luminal and abluminal faces of the lung microvascular endothelium but not on the apical surface of the alveolar epithelium. Staining for the integrin was generally negative in blood vessels of several systemic organs, although weak staining was evident in branches of the hepatic portal vein. The constitutive presence of the αvand β3mRNAs and the αvβ3-integrin in the lung microvascular bed suggests that gene transcription for the integrin is ongoing in lung vessels. Because it binds vitronectin, the lung vascular αvβ3-integrin may play a role in ligation of bloodborne, vitronectin-containing macromolecular complexes formed in inflammation.
Effect of steroid on hyperoxia-induced ICAM-1 expression in pulmonary endothelial cells
Authors: Suzuki Yukio , Nishio Kazumi , Takeshita Kei , Takeuchi Osamu , Watanabe Kenji , Sato Nagato , Naoki Katsuhiko , Kudo Hiroyasu , Aoki Takuya , Yamaguchi Kazuhiro
Published: December 2017

Intercellular adhesion molecule-1 (ICAM-1) of the vascular endothelium plays a key role in the development of pulmonary oxygen toxicity. We studied the effect of steroid on hyperoxia-induced ICAM-1 expression using cultured endothelial cells in vitro. Human pulmonary artery endothelial cells (HPAECs) were cultured to confluence, and then the monolayers were exposed to either control (21% O2-5% CO2) or hyperoxic (90% O2-5% CO2) conditions with and without a synthetic glucocorticoid, methylprednisolone (MP). MP reduced hyperoxia-induced ICAM-1 and ICAM-1 mRNA expression in a dose-dependent manner. Neutrophil adhesion to hyperoxia-exposed endothelial cells was also inhibited by MP treatment. In addition, MP attenuated hyperoxia-induced H2O2production in HPAECs as assessed by flow cytometry. An electrophoretic mobility shift assay demonstrated that hyperoxia activated nuclear factor-κB (NF-κB) but not activator protein-1 (AP-1) and that MP attenuated hyperoxia-induced NF-κB activation dose dependently. With Western immunoblot analysis, IκB-α expression was decreased by hyperoxia and increased by MP treatment. These results suggest that MP downregulates hyperoxia-induced ICAM-1 expression by inhibiting NF-κB activation via increased IκB-α expression.
Interstrain variation in murine susceptibility to inhaled acid-coated particles
Authors: Ohtsuka Yoshinori , Clarke Robert W. , Mitzner Wayne , Brunson Kiana , Jakab George J. , Kleeberger Steven R.
Published: December 2017

Epidemiologic studies have demonstrated a positive correlation between concentration of acid aerosol and increased morbidity and mortality in many urban environments. To determine whether genetic background is an important risk factor for susceptibility to the toxic effects of inhaled particles, we studied the interstrain (genetic) and intrastrain (environmental) variance of lung responses to acid-coated particle (ACP) aerosol in nine strains of inbred mice. A flow-past nose-only inhalation system was used to expose mice to ACPs produced by the cogeneration of a carbon black aerosol-sulfur dioxide (SO2) mixture at high humidity. Three days after a single 4-h exposure to ACPs or filtered air, mice underwent bronchoalveolar lavage, and cell differentials and total protein were determined as indexes of inflammation and epithelial permeability, respectively. To determine the effect of ACPs on alveolar macrophage (AM) function, lavaged AMs were isolated from exposed animals and Fc receptor-mediated phagocytosis was evaluated. Compared with air-exposed animals, there was a slight but significant exposure effect of ACPs on the mean number of lavageable polymorphonuclear leukocytes in C3H/HeJ and C3H/HeOuJ mice. ACP exposure also caused a significant decrease in AM phagocytosis. Relative to respective air-exposed animals, Fc receptor-mediated phagocytosis was suppressed in eight of nine strains. The order of strain-specific effect of ACPs on phagocytosis was C57BL/6J > 129/J > SJL/J > BALB/cJ > C3H/HeOuJ > A/J > SWR/J > AKR/J. There was no effect of ACP exposure on AM phagocytosis in C3H/HeJ mice. The significant interstrain variation in AM response to particle challenge indicates that genetic background has an important role in susceptibility. The effects of ACPs on AM function, inflammation, and epithelial hyperpermeability were not correlated (i.e., no cosegregation). This model may have important implications concerning interindividual variation in particle-induced compromise of host defense.
Targeted gene delivery to pulmonary endothelium by anti-PECAM antibody
Authors: Li Song , Tan Yadi , Viroonchatapan Ekapop , Pitt Bruce R. , Huang Leaf
Published: December 2017

To achieve efficient systemic gene delivery to the lung with minimal toxicity, a vector was developed by chemically conjugating a cationic polymer, polyethylenimine (PEI), with anti-platelet endothelial cell adhesion molecule (PECAM) antibody (Ab). Transfection of mouse lung endothelial cells with a plasmid expression vector with cDNA to luciferase (pCMVL) complexed with anti-PECAM Ab-PEI conjugate was more efficient than that with PEI-pCMVL complexes. Furthermore, the anti-PECAM Ab-PEI conjugate mediated efficient transfection at lower charge plus-to-minus ratios. Conjugation of PEI with a control IgG (hamster IgG) did not enhance transfection of mouse lung endothelial cells, suggesting that the cellular uptake of anti-PECAM Ab-PEI-DNA complexes and subsequent gene expression were governed by a receptor-mediated process rather than by a nonspecific charge interaction. Conjugation of PEI with anti-PECAM Ab also led to significant improvement in lung gene transfer to intact mice after intravenous administration. The increase in lung transfection was associated with a decrease compared with PEI-pCMVL with respect to circulating proinflammatory cytokine (tumor necrosis factor-α) levels. These results indicate that targeted gene delivery to the lung endothelium is an effective strategy to enhance gene delivery to the pulmonary circulation while simultaneously reducing toxicity.
Protein phosphatase inhibitors arrest cell cycle and reduce branching morphogenesis in fetal rat lung cultures
Authors: Taylor B. Keith , Stoops Tamara D. , Everett Allen D.
Published: December 2017

Protein phosphatase 2A (PP2A) is a key signal transduction intermediate in the regulation of cellular proliferation and differentiation in vitro. However, the role of PP2A in the context of a developing organ is unknown. To explore the role of PP2A in the regulation of lung development, we studied the effect of PP2A inhibition on new airway branching, induction of apoptosis, DNA synthesis, and expression of epithelial marker genes in whole organ explant cultures of embryonic (E14) rat lung. Microdissected lung primordia were cultured in medium containing one of either two PP2A inhibitors, okadaic acid (OA, 0–9 nM) or cantharidin (Can, 0–3,600 nM), or with the PP2B inhibitor deltamethrin (Del, 0–10 μM) as a control for a PP2A-specific effect for 48 h. PP2A inhibition with OA and Can significantly inhibited airway branching and overall lung growth. PP2B inhibition with Del did not affect lung growth or new airway development. Histologically, both PP2A- and PP2B-inhibited explants were similar to controls. Increased apoptosis was not the mechanism of decreased lung growth and new airway branching inasmuch as OA-treated explant sections subjected to the terminal deoxynucleotidyltransferase dUTP nick end labeling reaction demonstrated a decrease in apoptosis. However, PP2A inhibition with OA increased DNA content and 5-bromo-2′-deoxyuridine uptake that correlated with a G2/M cell cycle arrest. PP2A inhibition also resulted in altered differentiation of the respiratory epithelium as evidenced by decreased mRNA levels of the early epithelial marker surfactant protein C. These findings suggest that inhibition of protein phosphatases with OA and Can halted mesenchymal cell cycle progression and reduced branching morphogenesis in fetal rat lung explant culture.
Lipopolysaccharide induces relaxation in lung pericytes by an iNOS-independent mechanism
Authors: Speyer Cecilia L. , Steffes Christopher P. , Tyburski James G. , Ram Jeffrey L.
Published: December 2017

Lipopolysaccharide (LPS)-regulated contractility in pericytes may play an important role in mediating pulmonary microvascular fluid hemodynamics during inflammation and sepsis. LPS has been shown to regulate inducible nitric oxide (NO) synthase (iNOS) in various cell types, leading to NO generation, which is associated with vasodilatation. The purpose of this study was to test the hypothesis that LPS can regulate relaxation in lung pericytes and to determine whether this relaxation is mediated through the iNOS pathway. As predicted, LPS stimulated NO synthesis and reduced basal tension by 49% ( P < 0.001). However, the NO synthase inhibitors Nω-nitro-l-arginine methyl ester, aminoguanidine, and Nω-monomethyl-l-arginine did not block the relaxation produced by LPS. In fact, aminoguanidine and Nω-monomethyl-l-arginine potentiated the LPS response. The possibility that NO might mediate either contraction or relaxation of the pericyte was further investigated through the use of NO donor compounds; however, neither sodium nitroprusside nor S-nitroso- N-acetylpenicillamine had any significant effect on pericyte contraction. The inhibitory effect of aminoguanidine on LPS-stimulated NO production was confirmed. This ability of LPS to inhibit contractility independent of iNOS was also demonstrated in lung pericytes derived from iNOS-deficient mice. This suggests the presence of an iNOS-independent but as yet undetermined pathway by which lung pericyte contractility is regulated.
On measurement of brain elastic response in vivo
Authors: Walsh E. K. , Furniss W. W. , Schettini A.
Published: December 2017

The elastic response behavior of brain tissue in vivo has been shown to be sensitive to the physiological environment of the brain and thus represents a useful parameter for identifying effects of controlled changes on the system. Here we describe a method for measuring brain elastic response using an epidural pressure-depth transducer and a minimum number of insertions. The method also serves to identify the nonlinear response of brain tissue.
Sympathetic nervous system involvement in the lateral hypothalamic lesion syndrome
Authors: Opsahl C. A.
Published: December 2017

The role of the sympathetic nervous system in the lateral hypothalamic syndrome of body-weight loss was investigated. Bilateral electrolytic lesions of the lateral hypothalamus (LH) were performed in 90-day-old male albino rats. In experiment 1, the splanchnic nerves were resected at 35 days (right) and 70 days (left) postlesion. In experiment 2, bilateral adrenal demedullations were performed in a second group of rats with LH lesions (LH rats) at 35 days postlesion. The results indicated that lesions of the lateral hypothalamic area lowered body-weight maintenance levels to approximately 87% of nonlesion control values. Bilateral splanchnicetomy produced a significantly greater body-weight loss in nonlesion animals than in LH rats. Following adrenal demedullation, nonlesion rats also reduced body-weight levels whereas LH rats significantly increased weight-maintenance levels. In addition, the adrenal glands of LH rats with sham demedullations weighed significantly more than the adrenals of nonlesion-sham demedullated animals. These data are discussed in relation to metabolic-autonomic mechanisms that may play a role in LH lesion-induced weight loss.
Computer simulation of rat heart metabolism after adding glucose to the perfusate
Authors: Achs M. J. , Garfinkel D.
Published: December 2017

An experiment where perfused rat hearts receiving no substrate are suddenly given glucose with insulin in the perfusate is simulated with a computer model of cardiac energy metabolism. Mitochondrial metabolism is quantitatively reorganized under cytoplasmic control, with fatty acid oxidation undergoing a two-step decrease. There is an unspanning of the Krebs cycle (different reactions going at different rates) due primarily to slowing of alpha-ketoglutarate dehydrogenase; this ends when cytoplasmic glucose reaches a new steady state. Mitochondria in vitro are known to have higher pH than their surroundings; it is found here that this also holds in situ. Under these conditions, glycolysis is coherently substrate controlled, as is phosphofructokinase, usually considered the typical example of an allosteric enzyme. Limitations on simple methods of analyzing metabolic data of this type, e.g., use of lactate/pyruvate ratios to calculate NADH/NAD ratios, are discussed. Here a large volume of enzyme and other biochemical information has been integrated into a physiologically meaningful system.
A field and circuit thermodynamics for integrative physiology. I. Introduction to the general notions
Authors: Iberall A. S.
Published: December 2017

In this first of three articles on a physical basis for integrative physiology, statistical mechanical concepts are developed into a field thermodynamics. The development begins by comparing the different ways change is viewed in biology compared to physics. The Hamiltonian field concept unites the two. The requirements of a thermostatic description are introduced; then those of nonequilibrium thermodynamics are added. Conditions suitable for continuum, near-equilibrium analysis of systems are given; then the role of physical forces in organization is discussed. The development returns to statistical mechanics, and introduces conservation principles and equations of change for ensembles of interacting units. A general notion of systems and thermodynamic engines is discussed next, and a narrative account of the explanatory scope of field thermodynamics is given. Its applications to living systems are the subject of the subsequent two articles of this series.
A field and circuit thermodynamics for integrative physiology. II. Power and communicational spectroscopy in biology
Authors: Iberall A. S. , Soodak H. , Hassler F.
Published: December 2017

This paper continues the development begun in Part I (15), to show in what way it is meaningful to reduce biological phenomena to physical theory at any level of organization. The appropriate level-independent physics is comprised of thermostatics, thermodynamics of irreversible processes, statistical mechanics, and nonlinear mechanics. Generalized, these approaches lead to a spectroscopic description of the constellation of periodic processes that constitute the living states. The spectroscopic description is here applied also to the inputs received by living systems, from lethal, high-energy, nuclear particles and radiation to low-energy communicational signals that make up languages understandable at the various levels in an hierarchical system. The concept of language is then itself generalized, showing how the empirical relation discovered by Zipf can be derived from a thermodynamic basis. It is demonstrated that certain linguistic and statistical-mechanical distribution functions can be related. Applications of the field thermodynamic approach to two problems in transport phenomena are given in APPENDIX I; applications of field thermodynamics to language and communication are given in APPENDIX II.
Comparative aspects of brain barrier systems for nonelectrolytes
Authors: Cserr H. F. , Fenstermacher J. D. , Rall D. P.
Published: December 2017

Blood-brain and blood-CSF barriers to inulin were compared in 11 vertebrate species. Twenty hours after systemic administration, [14C]inulin penetrated into the central nervous system to an equivalent extent in mudpuppy, salamander (adult and larval), red sculpin, big skate, little skate, southern stingray, and Atlantic stingray with values for RB (dpm/g brain divided by dpm/ml plasma) in the range 0.01- 0.04 and for RCSF (dpm/ml CSF divided by dpm/ml plasma) from 0.02 to 0.04. These values are similar to those reported for mammals. For dogfish, nurse shark, and lemon shark, RB ranged from 0.04 to 0.09 and RCSF from 0.08 to 0.29 and for hagfish RB=0.12, indicating that barrier systems to inulin are poorly developed in sharks and possibly absent in hagfish. Analyses of radiolabeled urea and sucrose penetration into brain and CSF revealed further differences in shark barrier function. Brain barriers to insulin in dogfish and little skate developed with age; in nurse shark there was no detectable change in the inulin ratios over the weight range, 0.2-110 kg.
Angiotensin II infusion increases vasopressin, ACTH, and 11-hydroxycorticosteroid secretion
Authors: Ramsay D. J. , Keil L. C. , Sharpe M. C. , Shinsako J.
Published: December 2017

The effects of intravenous infusion of Asp1. Ile5-angiotensin II on blood pressure, plasma vasopressin, ACTH and 11-hydroxycorticosteroid levels and on plasma renin activity were studied in five trained, conscious dogs. The dogs were prepared with bilateral carotid loops. Infusion of angiotensin II at rates of 5, 10, and 20 ng/kg.min raised its plasma concentration from 23 +/- 7 to 48 +/- 8, 125 +/- 8, and 187 +/- 21 pg/ml, respectively. The lowest rate of infusion was mildly pressor, the two higher rates more so. All rates of infusion promptly increased vasopressin levels and depressed renin levels. The two higher rates also stimulated ACTH, although with a latency of 30-45 min. Since the rates of infusion of angiotensin II employed produced plasma levels within the physiological range, it is suggested that peripherally generated angiotensin II may play an important role in the regulation of vasopressin, and ACTH secretion.
Micropuncture studies of the osmoregulation in the nauplius of Artemia salina
Authors: Russler D. , Mangos J.
Published: December 2017

The osmoregulation of the nauplius of the brine shrimp, Artemia salina, was investigated using micropuncture and microanalytical techniques. The naupliar body fluid, hemolymph was hyposmotic to and had lower Na concentrations than the suspending medium for the range of medium salinities from 80 to 4,900 mM NaCl. In medium containing 20 mM NaCl, the hemolymph was hyperosmotic to the medium, with osmolarity of 101 +/- 8 mosmol/1 and with [Na] of 49 +/- 11 meq/1. Whereas the maximal observed NaCl concentration gradient between hemolymph and medium was 4,785 mM, during the incubation of nauplii in artificial seawater (osmolarity: 932 mosmol/1; and [Na]: 502 meq/1) the osmolarity and [Na] of the naupliar hemolymph were 161 +/- SD 16 mosmol/1 and 86 +/- 14 meq/1, respectively. The influx and efflux of Na between medium and hemolymph were measured using 22Na. The fluxes of this ion were temperature dependent. The main site of efflux of 22Na was the neck organ as was shown by experiments of differential recovery of 22Na introduced in the hemolymph. These studies demonstrate that the nauplius of A. salina has the ability to osmoregulate not only against high environmental salinities but also against low salinities approaching those of freshwater.
Osmosis, diffusion, convection
Authors: Soodak H. , Iberall A.
Published: December 2017

We present a tutorial on the mechanisms of and connections among osmosis, diffusion, and convection. For simplicity, we consider only two-component nonelectrolyte solutions under isothermal conditions. Further, we confine our attention to laminar convection with application to the case of flow through narrow channels, as might occur in membranes containing pores or slits. The application of equilibrium and near-equilibrium thermodynamics to flow processes is just like considerations of mechanics with friction, or hydrodynamics. The description of flow processes of more than two atomistic components, either solutions or suspensions, is identical in the dilute limit to the description we give, except possibly when the curvature of the flow field (at the velocity profile) is significant. Flow fields, therefore, naturally divide into three regimes: 1) "one-dimensional" flow fields, e.g., solutions or suspensions in extended regions, whose velocity profile is macroscopically flat (compared to the atomistic curvature); 2) flow fields with significant curvature, e.g., Poiseuille or turbulent fields; and 3) high curvature fields, e.g., narrow flow channels.
Twenty-four-hour pattern of circulation by radiotelemetry in the unrestrained dog
Authors: Ashkar E.
Published: December 2017

Eight dogs with indwelling transducers for continuous radiotelemetry of the hemodynamic function were acclimatized in an unisolated room under 12:12 LD photoperiods, in phase with the solar day cycle, and constant temperature (20 +/- 1 degrees C). Light was turned on at 0600 and off at 1800. Mean aortic blood flow (ABF), mean aortic blood pressure (ABP), heart rate (HR), respiratory rate (RR), and cardiac work (CW) were maximal at about 1800 and minimal at time 0600. Total peripheral resistance (TPR) was highest and stroke volume (SV) lowest at about 1200. The 24-h mean was for HR 77 beats/min, SV 28 ml/beat, RR 11 breaths/min, ABF 177 ml/min per kg body wt, ABP 102 Torr, TPR 3,960 dyn . s . cm-5, and CW 218 Torr . 1/min. The range of amplitude fluctuations for daytime means was about 6% for ABP and SV and 11-17% for all others. It is suggested that the homeostatic balance and timing of circulation is circadian time dependent.
Electrical and transport characteristics of skin of larval Rana catesbeiana
Authors: Cox T. C. , Alvarado R. H.
Published: December 2017

Carefully dissected, mounted, and bathed with Ringer solution, the larval bullfrog skin has a resistance of about 9,000 omega.cm2 and a stable transepithelial electrical potential of about 20 mV (inside +). A short-circuit current of about 2 microA.cm-2 is generated that is comparable in magnitude to the net inward flux of Na+. At open circuit the flux ratio equation for Na+ is not satisfied. Larval skin is less sensitive to ouabain, amiloride, and ADH than adult skin. The current-voltage (C-V) relationship across the preparation is not linear; there are distinct breaks in both the hyperpolarizing and hypopolarizing regions. The former break, at about +130 mV, corresponds with a break observed in adult skin that corresponds with ENa. The shunt resistance (RS) and active pathway resistance (RA) were estimated by C-V curve analysis and by ion substitution. The two methods yielded comparable values with RS about 11 k omega.cm2 and RA about 62 k omega.cm2. It is suggested that transport is limited by the number of entry sites for sodium at the apical border of transport cells.
Kinetics of bicarbonate/chloride exchange in dogfish erythrocytes
Authors: Obaid A. L. , Critz A. M. , Crandall E. D.
Published: December 2017

A stopped-flow rapid reaction apparatus was used to monitor changes in extracellular pH in dogfish (Mustelus canis) erythrocyte suspensions under conditions where dpH/dt was determined by the rate of HCO3-/Cl- exchange across the red cell membrane. Experiments were performed on erythrocytes suspended either in their own plasma or in elasmobranch Ringer solution over a range of temperatures from 5 to 35 degrees C. The exchange fluxes at 25 degrees C for red blood cells suspended in their own plasma (2.03 nmol/cm2-s) or in Ringer solution (2.00 nmol/cm2-s) are not significantly different and can be compared to those obtained under similar conditions for human red cell suspensions (0.910 nmol/cm2-s). The flux for dogfish erythrocytes suspended in Ringer solution was reduced by 80% after exposure of the cells to SITS. An Arrhenius plot of the exchange rate constant yielded an activation energy of about 13.2 kcal/mol. We conclude that 1) plasma has no inhibitory effect of HCO3-/Cl- exchange across the dogfish erythrocyte membrane or on activity of intraerythrocyte carbonic anhydrase, 2) HCO3-/Cl- exchange probably occurs via the same mechanism in fish and mammalian erythrocytes, and 3) the conversion of plasms HCO3- to CO2 in dogfish can be catalyzed by intraerythrocyte carbonic anhydrase.
Computer simulation of metabolism in pyruvate-perfused rat heart. II. Krebs cycle
Authors: Kohn M. C. , Achs M. J. , Garfinkel D.
Published: December 2017

A realistic metabolic model of the tricarboxylic acid cycle in the perfused rat heart was constructed to help explain the sequence of biochemical events regulating the metabolism of exogenous pyruvate following a large increase in work load. The unchelated Mg2+ level was the most important controlling factor. The resulting mixture of chelated and unchelated nucleotides and tribasic acids effected coordinated control of citrate synthase, aconitase, isocitrate dehydrogenase, succinyl CoA synthetase, fumarase, and nucleoside diphosphokinase, because Mg2+-chelates are generally substrates whereas unchelated species are inhibitors. Succinate dehydrogenase is largely controlled by the ubiquinone redox potential. The fluxes through alpha-ketoglutarate and malate dehydrogenases are largely dependent on thepyridine nucleotide redox potential, but the succinyl CoA-to-CoASH ratio strongly affects the former enzyme as well. The model predicts an accumulation of succinate during the transition to higher work output.
Catecholamine elevation in iron deficiency
Authors: Dillmann E. , Johnson D. G. , Martin J. , Mackler B. , Finch C.
Published: December 2017

Iron-deficient rats have increased blood and urinary catecholamines regardless of whether anemia is or is not present. The catecholamine response in both iron-deficient and control animals is largely temperature dependent, showing little difference at the isothermic temperature of 30 degrees C but a two- to threefold increase in iron-deficient animals over controls at lower temperatures. The iron-deficient rat is unable to maintain body temperature at 4 degrees C and this is independent of anemia or of food intake. When animals are run on the treadmill for 4 h, body temperatures increase but the difference observed at 4 degrees C between iron-deficient and control animals persists. The underlying abnormality in temperature regulation and in catecholamine response disappeared after 6 days of iron therapy.
Transferrin catabolism in mammalian species of different body sizes
Authors: Regoeczi E. , Hatton M. W.
Published: December 2017

Turnover of transferrin was measured in 62 mammals from 11 species (baboon, dog, goat, guinea pig, man, mouse, pig, rabbit, rat, rhesus monkey, and sheep) using iodinelabeled transferrin of homologous and/or heterologous origin. Protein turnover was determined either from the plasma protein-bound radioactivity curves or from the slopes of total body radiation. The volume of transferrin pool, expressed as equivalent milliliters of plasma, turned over per day correlated closely with species size (r = +0.977). Using the parabolic equation, y = axb, the constants for the relationship between body weight (x) and transferrin turnover (y) were a, 22.845; and b, 0.68. However, species of comparable weights with deviating transferrin turnovers do exist within the boundaries of this relationship. From a limited number of serum transferrin estimations in all species except for rhesus, six species appeared to have transferrin concentrations in a broad middle range (2.5-3.5 mg/ml). By comparison, dog and guinea pig had markedly lower, and pig and rat had markedly higher, serum transferrin concentrations.
Plasma angiotensin II: dipsogenic levels and angiotensin-generating capacity of renin
Authors: Mann J. F. , Johnson A. K. , Ganten D.
Published: December 2017

Activation of the renin-angiotensin system (RAS) or administration of angiotensin II (AII) will induce water intake. In the rat, the species in which the physiological mechanisms of thirst have been most thoroughly studied, the levels of circulating AII produced by systemic administration of dipsogenic doses of the octapeptide have not been established. Furthermore, the capacity of the endogenous RAS to generate AII sufficient to contribute to the production of a thirst state has not been well studied. In the present series of investigations, plasma levels of AII were determined following infusions of the peptide over a range of doses frequently employed in studies on thirst. In addition, a series of manipulations ranging from mild water deprivation or ingestion of a dry meal to ether stress of rats with malignant renal hypertension was applied to examine the capacity of the RAS to generate angiotensin. The results indicate that the endogenous RAS can readily produce the major effector peptide of the system so that circulating levels are well in excess of the dipsogenic threshold for AII.
Role of paraventricular and supraoptic nuclei in central cardiovascular regulation in the cat
Authors: Ciriello J. , Calaresu F. R.
Published: December 2017

To investigate the role of the paraventricular (PAH) and supraoptic (SON) nuclei in regulation of the cardiovascular system experiments were done in 26 cats anesthetized with alpha-chloralose, paralyzed, and artificially ventilated. Electrical stimulation of histologically verified sites in the region of the PAH and SON elicited increases in arterial pressure in bilaterally vagotomized animals and increases in heart rate both in spinal (C2) animals and in animals bilaterally vagotomized, In addition, stimulation of either the PAH or SON inhibited the reflex vagal bradycardia elicited by stimulation of the carotid sinus nerve (CSN) and bilateral lesions of these areas increased the magnitude of the response. On the other hand, stimulation and lesions of these hypothalamic regions did not alter the magnitude of the cardiovascular responses to stimulation of the aortic depressor nerve. These results demonstrate that stimulation of the PAH and SON elicit cardiovascular responses due to reciprocal changes in activity of the parasympathetic and sympathetic nervous systems and that these structures maintain a tonic inhibitory influence on the heart rate component of the CSN reflex.
Sodium balance during pregnancy in the rat
Authors: Churchi-l S. E. , Bengele H. H. , Alexander E. A.
Published: December 2017

The purpose of this study was to quantitate sodium balance during gestation in the rat (3 wk) to determine the time course of salt retention and to define the distribution of the retained salt. We have found that while sodium retention appears to begin during the 2nd wk, the bulk of retention occurs during the 3rd wk when the rat excretes only 67% of that ingested. Compared to that of nonpregnant, control rats, net retention for all of gestation was 9.8 meq. Despite a significantly higher sodium intake in pregnant rats, neither urinary nor fecal sodium excretion was different in pregnant and control rats. Fifty-nine percent of the retained sodium was found in the products of conception. Inulin space was increased by term from 19.7 to 25.4% of nonconceptus body weight. In pregnant rats a net retention of 6.3 meq of potassium was noted, 55% of which was found in the products of conception. We conclude that the rat retains sodium and potassium during pregnancy, predominantly in the third trimester. Over half of these salts are found within the conceptus products.
Hypothermia following injection of 2-deoxy-D-glucose into selected hypothalamic sites
Authors: Shiraishi T. , Mager M.
Published: December 2017

From our previous studies with 2-deoxy-D-glucose (2-DG) an inhibitor of glucose utilization, we postulated that the resultant intracellular glucopenia affects central neuronal pathways involved in the control of peripheral heat production. In this investigation, we have delineated these thermoregulatory sites by stereotaxically injecting microquantities of 2-DG into the hypothalamus of the rat and monitoring core temperature (Tre). After stabilization of Tre at a room temperature of 23 +/- 1 degree C, 20 microgram of 2-DG in 2 microliter was injected into 350- to 400-g rats. Significant decreases in Tre were noted after injections into the anterior hypothalamic, ventromedial, and dorsomedial nuclei as well as the lateral and posterior hypothalamic areas. Mean nadir Tre decreased 1.5 degrees C 1 h after, was significantly depressed 3.5 h after, and returned to basal values 4 h after administration of 2-DG into the ventral premammillary nucleus (PMV). Dose-dependent response was observed for injections into the PMV only. Of a total of 21 sites studied in the anterior and posterior hypothalamus, the PMV, an area of unknown physiological function, was the most sensitive to glucose deprivation.
Effect of lateral hypothalamic lesions on regulation of body weight and adiposity in rats
Authors: Milam K. M. , Stern J. S. , Storlien L. H. , Keesey R. E.
Published: December 2017

Obese and lean Zucker rats received bilateral electrolytic lesions of the lateral hypothalamus (LH) at 10 wk of age; control obese and lean rats were sham lesioned. After lesioning the body weights of both obese and lean animals were first reduced and then maintained until being killed (32 wk) at a stable percentage of the nonlesioned control levels (74.5 and 78.3%, respectively). Carcass analysis revealed that the adipose tissue mass was significantly lowered by LH lesions in both the obese and lean animals. Percent carcass fat of lesioned lean rats was less than that of controls (15.0 vs. 23.5%) due to the presence of slightly, but not significantly, smaller and fewer adipocytes. Though absolute levels of fat were likewise lowered in obese rats, their percent carcass fat remained at control levels (52.0 vs. 53.0%) due to equivalent decreases in other body compartments. In the lesioned rats the reduced levels of adipose tissue were associated with a significant reduction in adipocyte number; adipocyte size was unchanged. It is concluded that the lateral hypothalamus of obese Zucker rats participates in the regulation of body weight in the same manner as in lean rats. The differences noted in percent carcass fat between LH lesioned lean and obese Zucker rats are apparently related to the obese animal's known propensity to sequester energy in the form of lipid.
Thirst following water deprivation in humans
Authors: Rolls B. J. , Wood R. J. , Rolls E. T. , Lind H. , Lind W. , Ledingham J. G.
Published: December 2017

The effect of 24-h water deprivation and subsequent drinking on systemic fluid balance and subjective sensations has been determined in human beings. The deprivation caused significant intracellular and extracellular depletions, thirst, and a dry unpleasant tasting mouth. During rehydration, subjects drank 65% of their total intake within 2.5 min. The marked decrease in drinking rate thereafter, and the alleviation of thirst, occurred before plasma dilution had become significant. This attenuation of drinking was subjectively attributed to stomach fullness. Presystemic factors may therefore be important for drinking termination in humans. Within 20 min systemic deficits were removed, but intermittent drinking continued at a low rate, reportedly to alleviate unpleasant oral sensations, Following rehydration, the concentrated urine of hydropenia had disappeared. However, the excretion of solute-free water varied between subjects. Plasma renin activity was significantly elevated by water deprivation, while after rehydration this activity had decreased to levels not significantly different from predeprivation values.
P-wave morphology and atrial activation in the domestic fowl
Authors: Hill J. R. , Goldberg J. M.
Published: December 2017

The purpose of this study was to define the P-wave morphology in the open chest, anesthetized fowl, and to map the corresponding pattern of atrial epicardial activation. Using back lead electrocardiograms (ECG) recorded between the base of the neck and tail, seven P-wave morphologies were identified. Four of these morphologies were upright, two were inverted, and one was biphasic. Spontaneous conversion from one morphology to another was common. During the most common P-wave morphology, activation of the atrial epicardium was mapped by comparing the onset of up to 68 local electrograms with the onset of the P wave of the ECG. Pacemaker activity was found near the base of the left sinoatrial valve and preferential conduction was demonstrated caudally along the base of that valve and medially along the rostral border of the right atrium. Changes in P-wave morphology were shown to correspond with changing patterns of atrial activation. Spontaneous changes in P-wave morphology and epicardial activation indicate a labile pacemaker region in the bird and suggest a developmental stage of evolution similar to both their reptilian ancestors and to their mammalian counterparts.
Ventilation and acid-base balance during graded activity in lizards
Authors: Mitchell G. S. , Gleeson T. T. , Bennett A. F.
Published: December 2017

Arterial PCO2, hydrogen ion ([H+]a), and lactate ([L]a) concentrations, rates of metabolic CO2 production (VCO2) and O2 consumption (VO2), and effective alveolar ventilation (Veff) were determined in the lizards Varanus exanthematicus and Iguana iguana at rest and during steady-state treadmill exercise at 35 degrees C. In Varanus, VCO2 increased ninefold and VO2 sixfold without detectable rise in [L]a at running speeds below 1.0 to 1.5 km x h-1. In this range, Veff increased 12-fold resulting in decreased levels of PaCO2 and [H+]a. At higher speeds [L]a rose. Increments of 5 mM [L]a were accompanied by hyperventilation, reducing PaCO2 and thus maintaining [H+]a near its resting level. When [L]a increased further, [H+]a increased. Sustainable running speeds (0.3-0.5 km x h-1 and below) were often associated with increased VO2, VCO2, and [L]a in Iguana. Sixfold increases in VCO2 and 9-mM increments in [L]a were accompanied by sufficient increase in Veff (9-fold) to maintain [H+]a at or below its control level. When [L]a increased further, [H+]a increased. These results indicate that both lizard species maintain blood acid-base homeostasis rather effectively via ventilatory adjustments at moderate exercise intensities.
Coronary circulation in hearts from hibernating, normothermic, and cold-acclimated hamsters
Authors: Merrill G. F. , White J. T. , Krieger L. W.
Published: December 2017

We have investigated the influence of temperature, acute global ischemia, adenosine administration, and alterations in perfusion pressure on the coronary circulation of isolated, perfused spontaneously beating hearts from hibernating, normothermic, and cold-acclimated (nonhibernating) hamsters. No differences in heart rates were observed among groups at either 9 or 38 degrees C. Hearts from hibernating hamsters showed some differences in autoregulatory capacity at both the low and normal temperatures. All hearts exhibited similar responses to 30 s of global ischemia at both temperatures, with a marked reduction in the response at 9 degrees C. Similarly, the magnitude of the vasculature response to adenosine (250 micrograms) at 38 and 9 degrees C was equal in both normothermic and hibernating hearts perfused at 38 degrees C. Responses were abolished in all groups at 9 degrees C. We conclude that the altered ability of hibernating hearts to autoregulate is possibly due to intrinsic differences initiated by hibernation, while the responses to adenosine, and global ischemia are largely temperature-dependent effects.
Temperature-sensitive neurons in the preoptic region of sunfish
Authors: Nelson D. O. , Prosser C. L.
Published: December 2017

Single-unit, extracellular recordings were made from spontaneously active, thermosensitive neurons in the preoptic region of green sunfish acclimated to 25 degrees C. Activity of single cells was monitored during increases and decreases in local brain temperature over approximately a 10 degrees C range. Deep-body and skin temperatures were maintained at 25 degrees C. Of 276 neurons, 81% were insensitive, 17% were warm sensitive, and 2% cold sensitive. Warm responses were grouped into three basic types: exponential, linear, and nonlinear. All cold-sensitive neurons responded in a similar nonlinear manner. Mean levels of firing rate of thermosensitive neurons at 25 degrees C brain temperature ranged from 6 +/- 1.1 impulses/s to 22.7 +/- 10.8 impulses/s. Thermosensitivities were as high as 5.2 +/- 0.9 impulses . -1 . degrees C-1. Anatomic location of these neurons within the preoptic region appears random with some trend for the exponentially responding, warm-sensitive neurons to be located more medial than the other thermosensitive cell types. A small number of neurons were located in the ventrolateral telencephalon. In general, the thermosensitive responses observed resemble those found in other ectotherms and mammals with some exceptions.