bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of brain blood flow and permeability during acute hypertension
Authors: Baumbach Gary L. , Heistad Donald D.
Published: December 2017

Page H629: Gary L. Baumbach and Donald D. Heistad. “Heterogeneity of brain blood flow and permeability during acute hypertension.” Page H624: the legend for Fig. 6 should read, “Change in regional 125I-albumin during hypertension in cats with sympathetic denervation. * P < 0.05 vs. cerebrum (unpaired t test with Bonferroni correction).”
Altered phospholipid metabolism in pressure-overload hypertrophied hearts
Authors: Reibel D. K. , O'Rourke B. , Foster K. A. , Hutchinson H. , Uboh C. E. , Kent R. L.
Published: December 2017

The content and fatty acyl composition of phospholipids were examined in pressure-overload hypertrophied hearts. Cardiac hypertrophy was induced in rats by abdominal aortic constriction. Twenty-one days postconstriction the content of myocardial phosphatidylcholine (PC), sphingomyelin, and phosphatidylinositol (PI) was significantly elevated by 10, 10, and 20%, respectively. The essential fatty acid, linoleic acid, was markedly reduced in PC, phosphatidylethanolamine (PE), PI, and cardiolipin (CL) of hypertrophied hearts. The associated changes in fatty acyl composition were specific for the individual phospholipid class as evidenced by a significant elevation of palmitic acid in PC, docosahexaenoic acid in PE and oleic acid in CL. Alterations in fatty acyl composition of phospholipids were associated with no change in the composition of cardiac triglycerides, cardiac free fatty acids or serum lipids. The fatty acyl composition of phospholipids was also altered in pressure-overload hypertrophied hearts of cats, as evidenced by a reduction of linoleic acid and an elevation of arachidonic acid in total phospholipids. These findings demonstrate that changes in phospholipid metabolism occur in the pressure-overloaded mammalian heart. Such alterations may contribute to altered membrane function in the hypertrophied myocardium.
Effects of 4-aminopyridine on rate-related depression of cardiac action potentials
Authors: Gilmour R. F. , Salata J. J. , Davis J. R.
Published: December 2017

Canine cardiac Purkinje fibers and atrial trabeculae and rat and cat papillary muscles superfused with a hyperkalemic, hypoxic, and acidotic Tyrode solution were depolarized to membrane potentials (-70 to -60 mV) at which action potential amplitude declined as the coupling intervals of pacing stimuli were prolonged from 500 to 4,500 ms. The rate-related decline of action potential amplitude appeared to be due to time-dependent recovery of the early outward current rather than to a decrease in inward calcium current, since it was prevented by 4-aminopyridine (1.0 mM), but not by isoproterenol (1.0 microM), caffeine (5.0 mM), or CsCl (5-20 mM) and it was accompanied by an exponential increase of developed tension. Experiments using Purkinje fibers mounted in a single sucrose gap chamber demonstrated that the rate-related decline of action potential amplitude was maximal at membrane potentials between -70 and -40 mV and was negligible at less negative or more negative membrane potentials. These results may pertain to the mechanism for deceleration-dependent bundle branch block.
Mechanical control of initial lymphatic contractile behavior in bat's wing
Authors: Hogan R. D. , Unthank J. L.
Published: December 2017

The initial lymphatics of the bat's wing demonstrate spontaneous rhythmical contractions that contribute to the active formation of lymph. In the present study, modulation of lymphatic activity by mechanical factors was examined. Oil was injected to block the outflow tract of individual initial lymphatic bulbs to create a state of near isovolumetric contraction. Pulse pressure, base-line pressure, and contractile frequency were measured with the servo-null technique, while base-line pressure within the bulb was controlled by the infusion or withdrawal of fluid. Increasing the base-line luminal pressure from its resting level (near atmospheric pressure) produced an increase in pulse pressure up to an optimal level and then a subsequent decline in pulsatile strength. The magnitude of the pulsations changed by three to four times over the range of distending pressures. Contractile frequency increased 14% over the same range.
Distribution of capillary blood flow in rat kidney during postischemic renal failure
Authors: Vetterlein F. , Petho A. , Schmidt G.
Published: December 2017

Changes in distribution of intrarenal blood flow were studied in anesthetized rats during the acute phase of postischemic renal failure (1 h renal artery occlusion, 1 h reflow). Distribution of capillary plasma flow was determined by injecting fluorescein-isothiocyanate-globulin and lissamine-rhodamine-B200-globulin 1, 3, or 10 min prior to rapid freezing of the kidney. In histological sections it was possible to differentiate among the vessels perfused during the time of labeling because of their respective fluorescence. In these experiments all glomeruli became labeled within 1 min, although in contrast to the controls, the glomerular capillary network itself was not filled completely in the postocclusion organs. Incomplete labeling was far more pronounced, however, in the postglomerular network of the occlusion experiments. Due to this effect in the cortex and in the medulla, 11 and 58% of tissue, respectively, were found lying at a distance of more than 60 microns from the next vessel labeled after 1 min of dye circulation. In the control experiments there was no tissue within this distance. Prolonging the time of labeling up to 10 min caused little change in this pattern of distribution. In the occlusion experiments, the globulins were observed in nearly all Bowman spaces, but in less than half of the tubular lumina. The results strengthen the view that the ischemic insult leads primarily to disturbance of the postglomerular perfusion, which then results in trophic damage of the tubular system mainly within the renal medulla.
Carbachol inhibits electrophysiological effects of cyclic AMP in ventricular myocytes
Authors: Rardon D. P. , Pappano A. J.
Published: December 2017

Muscarinic agonists inhibit beta-adrenoceptor-mediated electrophysiological effects in mammalian cardiac ventricular tissues. However, the site or sites of interaction are not entirely clarified. To address this problem, the effect of carbachol on isoproterenol-, 3-isobutyl-1-methylxanthine-, and forskolin-induced action potential changes was examined in guinea pig ventricular myocytes. Following enzymatic dispersion, myocytes had a resting membrane potential of -81.3 +/- 3 mV in 5.4 mM K+ Tyrode solution, and stimulated action potentials were 348 +/- 17 ms in duration (n = 17). Elevated extracellular [K+] ([K+]o) depolarized the membrane 56.5 mV per 10-fold increase in [K+]o. The estimated intracellular K+ activity was 115.7 mM. Carbachol (10(-6) M) alone produced no electrophysiological changes but antagonized isoproterenol-, 3-isobutyl-1-methylxanthine-, and forskolin-induced action potential prolongation by 84 +/- 11, 88 +/- 17, and 83 +/- 14%, respectively. Transient depolarizations produced in isoproterenol (10(-8) M), 3-isobutyl-1-methylxanthine (10(-5) M), and forskolin (10(-7) M), but not those produced in ouabain (10(-6) M), were antagonized by carbachol (10(-6) M). These data show that enzymatically dispersed myocytes maintain pharmacological and electrophysiological properties similar to those of cells in tissues, carbachol antagonizes electrophysiological effects of isoproterenol, 3-isobutyl-1-methylxanthine, and forskolin, and carbachol inhibits cyclic AMP-mediated effects at a site or sites in the cyclic AMP cascade distal to the catalytic unit of adenylate cyclase.
Mechanical and inotropic reserve in conscious dogs with left ventricular hypertrophy
Authors: Fujii A. M. , Vatner S. F. , Serur J. , Als A. , Mirsky I.
Published: December 2017

We studied the left ventricular (LV) responses to infusions of norepinephrine and prenalterol, a specific beta 1-adrenergic receptor agonist, in conscious, chronically instrumented adult dogs with severe LV hypertrophy. The goal of this study was to determine the extent of compensation induced by LV hypertrophy in an animal model in which the pressure overload was gradually increased, as occurs in human pathological states. One to 2 yr after banding the ascending aorta of puppies, six dogs with severe LV hypertrophy (LV free-wall weight-to-body weight ratio 7.0 +/- 0.4 g/kg), and nine sham-operated littermates (LV free-wall weight-to-body weight ratio 4.0 +/- 0.2 g/kg) were studied. The dogs were instrumented with ultrasonic dimension crystals (to measure LV short-axis diameter and wall thickness), miniature LV pressure transducers, and LV and aortic catheters. In the control dogs norepinephrine (0.4 micrograms X kg-1 X min-1) increased LV systolic/diastolic pressure from 121 +/- 2/9 +/- 1 to 177 +/- 9/20 +/- 2 mmHg, mean arterial pressure from 97 +/- 2 to 143 +/- 9 mmHg, LV dP/dt from 3,363 +/- 123 to 5,174 +/- 343 mmHg/s, and mean systolic wall stress from 194 +/- 14 to 299 +/- 22 g/cm2, while mean velocity of circumferential fiber shortening (Vcf), (dD/dt/D)max, and heart rate did not change from base line. In dogs with LV hypertrophy norepinephrine increased LV pressure from 224 +/- 16/11 +/- 1 to 305 +/- 22/19 +/- 1 mmHg, mean arterial pressure from 90 +/- 2 to 132 +/- 4 mmHg, LV dP/dt from 3,246 +/- 156 to 5,619 +/- 345 mmHg/s, and mean systolic wall stress from 224 +/- 11 to 307 +/- 24 g/cm2.(ABSTRACT TRUNCATED AT 250 WORDS)
Catecholamines and the relationship between cerebral blood flow and glucose use
Authors: Tuor U. I. , Edvinsson L. , McCulloch J.
Published: December 2017

The effects of hypertension induced by norepinephrine and dopamine infusion on the relationship between local cerebral blood flow (CBF) and local glucose use (GU) were examined in rats with the use of quantitative autoradiographic techniques. After rats recovered from anesthesia, dopamine or norepinephrine was infused at a rate that ensured moderate hypertension [mean arterial blood pressure (MABP) approximately 150 mmHg]. During dopamine infusion (approximately 200 micrograms X kg-1 X min-1), overall CBF-to-GU ratio throughout the brain was elevated (P less than 0.0001) when compared with saline controls. In contrast, during norepinephrine infusion (approximately 10 micrograms X kg-1 X min-1), the overall CBF-to-GU relationship was not altered significantly. The differential effect of the catecholamines was a consequence of the marked increases in local CBF and moderate decreases in GU observed during dopamine infusion, whereas during norepinephrine administration CBF and GU were not significantly altered in most brain regions. Blood-brain barrier (BBB) permeability was increased during moderate hypertension induced by dopamine and not when induced by norepinephrine. During extreme hypertension (MABP greater than 165 mmHg), heterogeneous increases in CBF and BBB permeability occurred (e.g., in the cerebellum and thalamus). Thus the cerebrovascular response to catecholamine infusion was critically dependent on the agent administered, the level of hypertension achieved, and the brain region examined.
Vagal cold block in area postrema-lesioned dogs: interaction of vasopressin and sympathetic nervous system
Authors: Applegate R. J. , Hasser E. M. , Bishop V. S.
Published: December 2017

This study evaluated the interaction between arginine vasopressin (AVP) and the sympathetic nervous system (SNS) during bilateral vagal cold block (BVB) and the arterial baroreflex response to phenylephrine (PE) and exogenous AVP in conscious sham-operated (sham) and area postrema (AP)-lesioned mongrel dogs. The hemodynamic responses to ganglionic blockade (GB) and the vascular (V1) AVP receptor antagonist [d(CH2)5Tyr(Me)]AVP (AVPX) were similar in sham and AP-lesioned dogs. Elimination of the AVP pressor system by AVPX in sham dogs did not alter the pressor response to BVB, whereas subsequent blockade of the SNS by GB abolished the response to BVB. When GB was first imposed, however, it alone eliminated only 55% of the pressor response to BVB, whereas subsequent AVPX eliminated the remaining pressor response to BVB. In contrast, in AP-lesioned dogs, AVPX alone substantially reduced the pressor response to BVB. Additionally, the apparent contribution of each pressor system to the response to BVB was not enhanced in the absence of the other system, as had been seen in the sham dogs. These da ta indicate that during interruption of vagal afferent activity, reflexly released AVP appears to limit the reflex activation of the SNS. This interaction of AVP with the cardiopulmonary reflex is eliminated following ablation of the area postrema. Infusion studies with PE and AVP indicate that AVP significantly augments baroreflex inhibition of heart rate when compared with PE. Ablation of the area postrema did not alter the arterial pressure-heart rate relationship obtained with PE but eliminated the augmented response to AVP.(ABSTRACT TRUNCATED AT 250 WORDS)
mu-Opioid receptors in NTS elicit pressor responses via sympathetic pathways
Authors: Hassen A. H. , Feuerstein G.
Published: December 2017

We have evaluated the relative contributions of the sympathetic and parasympathetic nervous systems to the increased mean arterial pressure (MAP) and heart rate (HR) elicited by the selective mu-agonist D-Ala2, MePhe4, Gly-ol5 enkephalin (DAGO) following microinjection (100 nl) into the nucleus of tractus solitarius (NTS) of anesthetized, artificially ventilated Sprague-Dawley rats. The effects of anesthesia and central opioid-receptor activation on baroreflex function were also examined. All cardiovascular responses elicited by DAGO were eliminated by complete C1 spinal transection. Pretreatment with the alpha-adrenergic antagonist phentolamine attenuated the increase in MAP, but not the tachycardia; the beta-blocker propranolol abolished the tachycardia but not the pressor response to DAGO. Adrenalectomy, vagotomy, or pretreatment with atropine methyl nitrate were all without effect. Baroreflexes were attenuated in animals anesthetized with pentobarbital sodium, but were present in urethan-anesthetized rats. DAGO attenuated the increases in MAP and HR elicited following carotid occlusion, but not the bradycardia elicited by a phenylephrine-induced pressor response. These data indicate that mu-receptors in the NTS elicit cardiovascular responses that are mediated by increased sympathetic nerve activity, and accompanied by selective attenuation of baroreflex function.
Mechanisms underlying enhanced capillary filtration induced by platelet-activating factor
Authors: Harris N. R. , Granger D. N.
Published: December 2017

Fluid filtration rate with respect to surface area (Jv/S) from rat mesenteric capillaries was measured before and after platelet-activating factor (PAF) superfusion, a model of acute inflammation. Jv/S increased from a baseline value of 0.015 +/- 0.003 to 0.033 +/- 0.003 micron/s (n = 7 rats, P < 0.01) during PAF superfusion. Measurements of arteriolar pressure with a servo-nulling pressure system suggest that the dominant factor causing the increase in Jv/S during PAF superfusion is increased capillary permeability, rather than an increase in pressure. Jv/S did not increase when PAF superfusion was preceded by administration of the radical-scavenging enzymes catalase and superoxide dismutase, implicating a role for oxygen radicals in the PAF-induced capillary filtration. In another series of studies, three experiments were performed, i.e., PAF superfusion alone or PAF superfusion plus treatment with either a soluble form of sialyl-Lewisx oligosaccharide (SLex) or a nonbinding form of SLex (SLN). These experiments revealed that the increased Jv/S normally elicited by PAF is significantly blunted by administration of soluble SLex but not by the control oligosaccharide SLN. The results of this study invoke a role for oxygen free radicals and selectins (ligands for SLex) in the enhanced capillary fluid filtration elicited by PAF.
Changes of atrial natriuretic peptide in brain areas of rats with chronic myocardial infarction
Authors: Hu K. , Gaudron P. , Bahner U. , Palkovits M. , Ertl G.
Published: December 2017

We measured immunoreactive atrial natriuretic peptide (ANP) in 18 selected, microdissected brain areas. Rats were studied 8 wk after coronary ligation or sham operation or as nonoperated control animals. In separate animals, hemodynamic and plasma parameters were measured. Rats with myocardial infarction had marked elevated right atrial and left ventricular end-diastolic pressure (2.6 +/- 0.6 and 16.2 +/- 3.1 mmHg, respectively; n = 15) vs. sham-operated rats (1.3 +/- 1.0 and 5.5 +/- 1.2 mmHg, n = 14; P < 0.05) and depressed maximal rate of pressure development (9,613 +/- 980 vs. 15,600 +/- 2,027 mmHg/s; P < 0.05) but similar arterial pressure (126 +/- 4 vs. 124 +/- 3 mmHg; P > 0.05). After myocardial infarction (n = 10), plasma ANP, renin activity, and angiotensin (ANG) II were elevated (53.1 +/- 16.2 pg/ml, 10.7 +/- 2.5 ng ANG I ml-1 h-1, and 219.6 +/- 11.0 fmol/ml, respectively) vs. sham rats (12.0 +/- 2.2 pg/ml, 5.7 +/- 0.7 ng ANG I ml-1, h-1, and 142.9 +/- 9.4 fmol/ml; n = 10; P < 0.05), whereas vasopressin and aldosterone levels remained unchanged among groups. In rats with myocardial infarction, a substantial decrease of ANP was found in the medial preoptic nucleus, the supraoptic nucleus, the subfornical organ, the paraventricular nucleus, and the locus ceruleus. These nuclei are involved in electrolyte, and fluid homeostasis, blood pressure regulation, and modulation of neuroendocrine systems. The mechanism of this reduction and the consequences for systemic adaption or decompensation remain unclear. However, the data suggest that myocardial infarction and chronic left ventricular dysfunction may induce changes of a neurotransmitter in brain.
Aquaporin-1 in plasma membrane and caveolae provides mercury-sensitive water channels across lung endothelium
Authors: Schnitzer J. E. , Oh P.
Published: December 2017

Classically, water transport across endothelium of the continuous type found in the microvessels of many organs such as lung was thought to occur almost completely via the paracellular pathway through intercellular junctions. Direct transmembrane and transcellular transport was considered to be minimal. In this study, we focused on the critical transport interface in direct contact with the circulating blood by purifying luminal endothelial cell plasma membranes directly from rat lungs and then isolating the noncoated plasmalemmal vesicles or caveolae from these membranes. Immunoblotting of these fractions showed that the transmembrane water channel protein aquaporin-1 was amply expressed on the endothelial cell surface at levels comparable to rat erythrocyte plasma membranes. It was found concentrated, but not exclusively, in caveolae. The functional role of these water channels in transport was examined in rat lungs perfused in situ with tritiated water by testing known inhibitors of aquaporin-1-mediated transmembrane water transport. Mercurial sulfhydryl reagents such as HgCl2 reversibly reduced tritiated water uptake without affecting small solute transport. Just like certain epithelia, endothelia might express physiologically relevant amounts of aquaporin-1 on their cell surface to permit direct, mercurial-sensitive, transcellular transport of water.
Chronic increases in blood flow upregulate endothelin-B receptors in arterial smooth muscle
Authors: Barber D. A. , Michener S. R. , Ziesmer S. C. , Miller V. M.
Published: December 2017

Experiments were designed to characterize endothelin receptors in arteries after chronic increases in blood flow. A fistula was created between the femoral artery and vein in one hindlimb of dogs; contralateral blood vessels were sham operated. Sham- and fistula-operated arteries were removed 6 wk postoperatively. Some arteries were prepared for measurement of isometric force or for isolation of membrane proteins. Other arteries were used for histological staining with an endothelin-B (ETB) receptor antibody. In arteries suspended for the measurement of isometric force, endothelin-1 produced concentration-dependent increases in tension that were significantly greater in fistula- than in sham-operated arteries without endothelium. The ETB-receptor-selective peptide sarafotoxin S6c produced concentration-dependent increases in tension only in fistula-operated arteries. In receptor-binding studies of membrane proteins, Scatchard analysis of saturation binding with 125I-labeled endothelin-1 (125I-endothelin-1) indicated that the total number of receptors was greater in fistula-operated arteries; affinity was threefold less in fistula- than in sham-operated arteries. Competitive displacement of 125I-endothelin-1 by endothelin-3 was significant for a two-site model in membranes prepared from sham-and fistula-operated arteries. Competitive inhibition of 125I-endothelin-1 binding by sarafotoxin S6c was significant for a one-site binding model in all arteries. Sarafotoxin S6c binding sites were elevated significantly in fistula-operated arteries. Immunohistochemical staining for the ETB receptor was significantly greater in both the endothelium and smooth muscle of fistula- than in sham-operated arteries. These results suggest that chronic increases in blood flow upregulate endothelin receptors, including ETB receptors in arterial smooth muscle.
THE RELATION BETWEEN THE DECOMPOSITION-TENSION OF SALTS AND THEIR ANTIFERMENTATIVE PROPERTIES
Authors: McGuigan Hugh
Published: December 2017

Line 9 on page 446, Volume X, should read:

"addition of the neutral salts of weak monobasic, dibasic, and tribasic acids."
STUDIES ON THE ULTRAFILTRATION AND ELECTRODIALYSIS OF INSULIN SOLUTIONS
Authors: Taylor T. C. , Braun C. E. , Scott E. L.
Published: December 2017

Contribution No. 485
STUDIES ON ADRENAL INSUFFICIENCY
Authors: Rogoff J. M. , Stewart G. N.
Published: December 2017

The first sentence on page 166, No. 1 of this volume (LXXXVIII) should read as follows:

As in dogs, the period of good health is usually 2 to 3 days shorter than the survival period, regardless of the duration of survival.
CAROTID SINUS REFLEXES TO THE RESPIRATORY CENTER
Authors: Schmidt Carl F.
Published: December 2017

Pages 100, 101, 107, 109, 112: Figures 3, 5, 9, 10, 11, and 15 have been reprinted to show greater detail.
CAROTID SINUS REFLEXES TO THE RESPIRATORY CENTER
Authors: Schmidt Carl F.
Published: December 2017

Pages 121, 124, 125: Figures 2, 5, and 6 have been reprinted to show greater detail.
ELECTROLYTES IN NERVE
Authors: Fenn W. O. , Cobb Doris M. , Hegnauer A. H. , Marsh B. S.
Published: December 2017

On pages 85 and 89 of Volume 110, due to an error by the senior author, the figures quoted for calcium in the last two columns of table 4 and the third column of table 5 are 10 times too high.
BLOOD LIPIDS DURING PREGNANCY IN GUINEA PIGS
Authors: Boyd Eldon M. , Fellows Marvel-Dare
Published: December 2017

On page 635 (four lines from bottom) for the word lipemia read lipopenia.—Ed.
CALCULATION OF CARDIAC OUTPUT FROM BLOOD PRESSURE MEASUREMENTS BEFORE AND AFTER MEALS
Authors: Bazett H. C. , Scott J. C. , Maxfield M. E. , Blithe M. D.
Published: December 2017

Volume 116, No. 3

On page 557, figure 5, the single aberrant value referred to in the text has been obliterated by the printer. The value was obtained by calculation and was 2.78 liters per square meter per minute 24 minutes after the middle of the meal.
A COMPARISON OF THE EFFECTS OF 11-DESOXYCORTICOSTERONE ACETATE AND 17-HYDROXY-11-DEHYDRO-CORTICOSTERONE IN PARTIALLY DEPANCREATIZED RATS
Authors: Ingle Dwight J. , Thorn George W.
Published: December 2017

Volume 132, page 674. In figure 2 of the paper: A Comparison of the Effects of 11-Desoxycorticosterone Acetate and 17-Hydroxy-11-Dehydro-Corticosterone in Partially Depancreatized Rats, by Dwight J. Ingle and George W. Thorn, the values for "urinary glucose" are expressed in tenths of grams. They should be expressed in grams.
Estimation of tissue protein synthesis in rats fed diets labeled with (U-14C)tyrosine
Authors: Harney ME , Swick RW , Benevenga NJ
Published: December 2017

The rate of liver and muscle protein synthesis has been measured in 27 rats after feeding L-[U-14C]tyrosine in L-amino acid diets prepared as agar gels. Constant specific activity of the free tyrosine pool, as indicated by constant excretion of 14CO2, was reached within 2 h of feeding and was maintained for the remaining 6 h of the 8-h experiment. Muscle protein synthesis was decreased (P less than 0.05) in rats fed a 0.3% methionine diet compared with rats fed this diet supplemented with 0.51% cystine (fractional rate of synthesis, ks: 0.098 vs. 0.121). No effect (P greater than 0.05) of these diets on liver protein synthesis was observed (ks: 0.603 vs. 0.532). Protein synthetic rate was also determined by the constant-intravenous infusion technique in 17 rats fed unlabeled diets. The two techniques gave similar estimates. Restraint of the rats or the infusion of saline had no measurable effect on the rate of protein synthesis in rats fed labeled diets. This feeding technique is essentially equivalent to the constant-infusion technique and offers an easier, more physiological approach to achieving a steady state.
Gastric A-cell function in normal dogs
Authors: Munoz-Barragan L , Blazquez E , Patton GS , Dobbs RE , Unger RH
Published: December 2017

Glucagon release from the gastric fundus and pancreas were compared in normal dogs by measuring glucagon in plasma from a major gastroepiploic vein, the superior pancreaticoduodenal vein, and the inferior vena cava. In 32 dogs in the basal state, gastric vein glucagon averaged 97 +/- 40 pg/ml, not significantly different from the 93 +/- 41 pg/ml level in the vena cava. Pancreaticoduodenal vein glucagon averaged 250 +/- 32 pg/ml (P less than 0.001). Intravenous arginine infused in four dogs caused a rise in mean gastric vein glucagon to 210 +/- 33 pg/ml within 3 min, and glucagon remained between 53 and 98 pg/ml above the vena caval level thereafter. In the gastric vein, the rise in glucagon was significantly greater than in the vena cava at 3, 5, and 10 min (P less than 0.05), but was far less than in the pancreaticoduodenal vein where glucagon rose to 1,295 +/- 379 pg/ml at 1.5 min. Evidence of modest gastric glucagon release was observed after the intragastric instillation of arginine, but not during insulin or phloridzin-induced hypoglycemia. It was concluded that in normal dogs under the circumstances studied, the gastric fundus is not a major source of circulating glucagon.
Single-nephron function and renal oxygen consumption during rapid volume expansion
Authors: Weinstein SW , Szyjewicz J
Published: December 2017

Isotonic volume expansion reduces net filtrate reabsorption in the proximal tubule while increasing it in Henle's loop. To determine the role oxidative metabolism plays in these processes, experiments were performed on rats initially hydropenic and then rapidly volume expanded with isotonic Ringer solution. Whole-kidney sodium reabsorption, oxygen consumption, and single-nephron function were measured simultaneously. During volume expansion, net renal sodium reabsorption increased concomitantly with a fall in oxygen consumption and a reduction in proximal tubular absolute filtrate reabsorption. The increase in quantity of nonreabsorbed filtrate delivered into the loop of Henle greatly exceeded the amount excreted in the urine. Thus, filtrate reabsorption by the distal nephron segments increased. These data provide evidence that acute volume expansion reduces oxygen-dependent active solute transport in the proximal tubule. The increase noted in distal nephron sodium reabsorption appears nonoxygen dependent, energized by anaerobic glycolysis or occurring passively.
Ischemia in isolated interventricular septa: mechanical events
Authors: Shine KI , Douglas AM , Ricchiuti N
Published: December 2017

Isolated blood-perfused rabbit interventricular septa were adapted for studies of global ischemia by enclosure in a constant-humidity nitrogen atmosphere. During ischemia, developed tension (DT) and maximal rate of relaxation (-dP/dt) declined monoexponentially, lambda = 0.39 min-1 at 37 degrees C and 72 beats/min with a Q10 of 1.4 for DT and a Q10 of 1.9 for -dP/dt. After a 60- to 90-s delay the maximal rate of tension development (+dP/dt) declined at the same rate as DT. Time-to-peak tension (TPT) shortened immediately with ischemia but action potential duration shortened after 60-90 s. Calcium at a concentration of 5 mM slowed the rate of decline of +dP/dt to lambda = 0.26 min-1. Upon reperfusion after 10 min of ischemia the rates of recovery of DT, +dP/dt, and -dP/dt were similar, lambda = 0.21-0.23 min-1, and were not temperature dependent. The magnitude of recovery was 10-17% less at 37 degrees C than 28 degrees C. Potassium at a concentration of 10 mM did not alter the rate of decline of mechanical function, but significantly (P less than 0.01) increased the magnitude of mechanical recovery. The results suggest depletion and/or repletion of single compartments as the rate-limiting steps in ischemia and reperfusion.
Unidirectional uptake of iron across intestinal brush border
Authors: Sheehan RG
Published: December 2017

To define the significance of the uptake step by unidirectional uptake of iron was measured on proximal small intestintestinal segments from Nembutal-anesthetized rats. The method employed a nonabsorbable marker of adherent incubating medium, and the studies were performed during the linear time period of instantaneous uptake. Uptake was linear over the concentration range 0.1-10 mM, from three iron complexes. The rate varied with the bioavailability of the iron in each complex. The Q10 was 1.0-1.3. Uptake rates were similar in all segments of small intestine. Uptake was not increased in segments from iron-deficient animals or rats with hemolytic anemia. Cobalt did not inhibit the uptake rate. These studies demonstrate that the uptake of nonheme iron by the small intestinal mucosal cell is by passive diffusion and further indicate that the uptake step does not contribute significantly to the mucosal control of iron absorption.
Compensatory phosphaturia after unilateral nephrectomy in the rat
Authors: Lehne C , Coe FL
Published: December 2017

Within 24 hr after unilateral nephrectomy, fractional excretion of phosphate (FEp) by the remaining kidney is markedly increased. This increase in FEp occurs in throparathyroidectomized rats receiving fixed replacement doses of parathyroid hormone and, therefore, cannot be due to secondary hyperparathyroidism occurring in response to unilateral nephrectomy. In the avsence of any hormone replacement, the increase in FEp is much reduced, but still present. The increase in FEp cannot be ascribed to depression of overall tubular sodium reabsorption because it could be demonstrated in the absence of an increase in FENa. Phosphaturia following unilateral nephrectomy in the rat appears to be part of the complex of events that occur after acute reduction of renal mass; the exact mechanisms of its genesis are uncertain.
Na-K-ATPase localization in teleost urinary bladder by [3H]ouabain autoradiography
Authors: Renfro JL , Miller DS , Karnaky KJ  , Kinter WB
Published: December 2017

Previous studies on the urinary bladder of the seawater-acclimated winter flounder (pseudopleuronectes americanus) demonstrated that active Na and Cl transport were ouabain sensitive. This suggested a relationship between the Na pump and Na-K-ATP-ase. The specific binding of [H]ouabain to Na-K-ATPase provides a means of localizing the site of active Na transport. In isolated bladders, a positive linear correlation (r= 0.89) was found between the active Na transport rate and the Na-K-ATPase activity. Ouabain binding by the bladder surface appeared to be saturable and relatively specific, e.g., was reduced by a high K concentration. When only the mucosal side of the bladder was exposed to 5 muM ouabain, both inhibitory effects and binding were small and are explained by finite permeability of the bladder to ouabain. In contrast, binding and inhibitory effects from the serosal side were much greater. Autoradiographs demonstrated that [3H]ouabain was bound only to the serosal side of the epithelial cells. Ultrastructural examination revealed that the area of ouabain binding coincided with the basal and lateral plasma membranes.
Acid-base regulation in pregnancy
Authors: Lim VS , Katz AI , Lindheimer MD
Published: December 2017

Plasma bicarbonate decreases during normal pregnancy. To assess what roles increased extra cellular volume or alterations in parathyroid hormone levels (iPTH) have in the maintenance of this decrement, we evaluated acid-base metabolism in eleven 3rd-trimester women. Base-line pH and PCO2 were 7.44 and 27.3 mmHg, respectively. Mean tubular reabsorption of phosphate was 93% and baseline iPTH levels were similar to those of nonpregnant subjects. During the slow infusion of hypertonic NaHCO3, a urinary threshold of HCO3- (THCO3) appeared at a mean plasma level of 18.9 meq/liter, but as plasma HCO3- increased progressively, its renal reclamation was almost complete and there was no evidence of either splay or tubular maximum, even when filtered loads of HCO3- reached 5 meq/min. Urine acidification was normal and distal [H+] secretory ability( deltaidification was normal and distal [H+] secretory ability (delta urinary PCO2) was similar to that reported in nongravid subjects. In metabolic balance studies blood pH and plasma HCO3- increased (P less than .01 and less than .02, respectively) when the women changed from a high- to a low-sodium diet. Mechanisms by which decreased plasma bicarbonate levels are maintained during gestation are discussed.
Role of phospholipase C and tyrosine kinase systems in growth response of human airway smooth muscle cells
Authors: De S. , Zelazny E. T. , Souhrada J. F. , Souhrada M.
Published: December 2017

The primary culture of confluent human airway smooth muscle (ASM) cells were exposed up to 5 days to human recombinant interleukin (IL)-1 beta in the presence of indomethacin and 1% fetal bovine serum. The proliferation was assessed by a [3H]thymidine incorporation and direct cell count. We found that IL-1 beta significantly increased thymidine incorporation into and cell count of ASM cells in a concentration-dependent manner. Pretreatment of cells with specific polyclonal antibodies against platelet-derived growth factor (PDGF-BB homodimer) completely inhibited the IL-1 beta-induced increase in thymidine incorporation. The PDGF-BB, at the concentrations of 1.5 and 2.5 ng/ml, stimulated the proliferation of ASM cells. The proliferation action of IL-1 beta was potentiated when PDGF-BB was added into the medium in combination with IL-1 beta. Pretreatment of cells with genistein (0.37 microM), a specific tyrosine kinase inhibitor, attenuated the proliferative effect of IL-1 beta and PDGF-BB. To clarify whether these growth stimuli (IL-1 beta and PDGF-BB) activated phospholipase C (PLC), we examined the formation of phosphatidylinositols. We observed that both agents significantly increased phosphoinositide turnover. In contrast, genistein pretreatment (0.37 microM) prevented formation of inositol 1,4,5-trisphosphate (IP3), as induced by IL-1 beta and/or PDGF-BB. This study demonstrates that both IL-1 beta and PDGF-BB could induce proliferation of ASM cells through the activation of tyrosine kinase and PLC, which in turn stimulate the formation of IP3, a second messenger molecule.
Beta-adrenergic agonists attenuate fibroblast-mediated contraction of released collagen gels
Authors: Mio T. , Adachi Y. , Carnevali S. , Romberger D. J. , Spurzem J. R. , Rennard S. I.
Published: December 2017

The effects of beta-adrenergic agonists on fibroblast-mediated collagen gel contraction were investigated. beta-Agonists isoproterenol and epinephrine significantly attenuated fibroblast-mediated gel contraction in a concentration-dependent manner, whereas alpha-agonist norepinephrine had no effect. The biologically active form of isoproterenol, (-)-isoproterenol, was 10-fold more effective than the optical isoform, (+)-isoproterenol. beta-Antagonists sotalol and propranolol reversed the attenuation caused by 10(-7) M isoproterenol or epinephrine at the concentration of 10(-7) M or 10(-6) M, but the alpha-antagonist phentolamine did not. However, beta1- or beta2-specificity of these effects is not clear. Isobutyl methylxanthine augmented the effect of isoproterenol and also prolonged the duration. Two reagents which are known to increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP), prostaglandin E2 and dibutyryl adenosine 3',5'-cyclic monophosphate, attenuated gel contraction in a concentration-dependent manner. These data suggest that the fibroblast-mediated collagen gel contraction can be modulated by beta-adrenergic agonists and that the effect depends on cAMP.
Effects of acute and chronic hypoxia on rat lung cyclooxygenase
Authors: Chida M. , Voelkel N. F.
Published: December 2017

Cyclooxygenase-2 (COX-2) is an inducible cyclooxygenase enzyme and may play an important role in the pathogenesis of lung injury and in pulmonary vascular remodeling. In this study we determined the effects of acute or chronic hypoxia on COX-2 induction and its modulation by .NO and adenosine 3'-5'-cyclic monophosphate (cAMP). Isolated perfused rat lungs were exposed to a normoxic gas mixture or a hypoxic gas mixture for 3 h. Northern blot analysis showed that 3 h of acute hypoxia were sufficient to increase COX-2 but not COX-1 transcripts in the lung. COX-2 expression induced by acute hypoxia was enhanced by an inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester, and was suppressed by sodium nitroprusside, meclofenamate, and H-7 (an inhibitor of protein kinase A and C). COX-2 expression was also enhanced by dibutyryl cAMP and iloprost, a prostacyclin analogue. In contrast, 2 wk of chronic hypobaric hypoxia did not enhance COX-2 expression in the lung, but increased COX-2 protein levels, as assessed by Western blots. We conclude that acute hypoxia induces COX-2 gene expression in rat lung and that COX-2 induction by acute hypoxia is modulated by .NO, cAMP, and cyclooxygenase products. In particular, prostacyclin produced by the lung during hypoxia or shear stress induces lung COX-2 expression via a positive feedback mechanism.
Mechanisms of GM-CSF increase by diesel exhaust particles in human airway epithelial cells
Authors: Boland Sonja , Bonvallot Véronique , Fournier Thierry , Baeza-Squiban Armelle , Aubier Michel , Marano Francelyne
Published: December 2017

We have previously shown that exposure to diesel exhaust particles (DEPs) stimulates human airway epithelial cells to secrete the inflammatory cytokines interleukin-8, interleukin-1β, and granulocyte-macrophage colony-stimulating factor (GM-CSF) involved in allergic diseases. In the present paper, we studied the mechanisms underlying the increase in GM-CSF release elicited by DEPs using the human bronchial epithelial cell line 16HBE14o−. RT-PCR analysis has shown an increase in GM-CSF mRNA levels after DEP treatments. Comparison of the effects of DEPs, extracted DEPs, or extracts of DEPs has shown that the increase in GM-CSF release is mainly due to the adsorbed organic compounds and not to the metals present on the DEP surface because the metal chelator desferrioxamine had no inhibitory effect. Furthermore, radical scavengers inhibited the DEP-induced GM-CSF release, showing involvement of reactive oxygen species in this response. Moreover genistein, a tyrosine kinase inhibitor, abrogated the effects of DEPs on GM-CSF release, whereas protein kinase (PK) C, PKA, cyclooxygenase, or lipoxygenase inhibitors had no effect. PD-98059, an inhibitor of mitogen-activated protein kinase, diminished the effects of DEPs, whereas SB-203580, an inhibitor of p38 mitogen-activated protein kinase, had a lower effect, and DEPs did actually increase the active, phosphorylated form of the extracellular signal-regulated kinase as shown by Western blotting. In addition, cytochalasin D, which inhibits the phagocytosis of DEPs, reduced the increase in GM-CSF release after DEP treatment. Together, these data suggest that the increase in GM-CSF release is mainly due to the adsorbed organic compounds and that the effect of native DEPs requires endocytosis of the particles. Reactive oxygen species and tyrosine kinase(s) may be involved in the DEP-triggered signaling of the GM-CSF response.
Lysosomes from rabbit type II cells catabolize surfactant lipids
Authors: Rider Evelyn D. , Ikegami Machiko , Pinkerton Kent E. , Peake Janice L. , Jobe Alan H.
Published: December 2017

The role of a lysosome fraction from rabbit type II cells in surfactant dipalmitoylphosphatidylcholine (DPPC) catabolism was investigated in vivo using radiolabeled DPPC and dihexadecylphosphatidylcholine (1,2-dihexadecyl- sn-glycero-3-phosphocholine; DEPC), a phospholipase A1- and A2-resistant analog of DPPC. Freshly isolated type II cells were gently disrupted by shearing, and lysosomes were isolated with Percoll density gradients (density range 1.0591–1.1457 g/ml). The lysosome fractions were relatively free of contaminating organelles as determined by electron microscopy and organelle marker enzymes. After intratracheal injection of rabbits with [3H]DPPC and [14C]DEPC associated with a trace amount of natural rabbit surfactant, the degradation-resistant DEPC accumulated 16-fold compared with DPPC in lysosome fractions at 15 h. Lysosomes can be isolated from freshly isolated type II cells, and lysosomes from type II cells are the primary catabolic organelle for alveolar surfactant DPPC following reuptake by type II cells in vivo.
Enhanced anti-influenza activity of a surfactant protein D and serum conglutinin fusion protein
Authors: Hartshorn Kevan L. , Sastry Kedarnath N. , Chang Donald , White Mitchell R. , Crouch Erika C.
Published: December 2017

We previously demonstrated that bovine serum conglutinin has markedly greater ability to inhibit influenza A virus (IAV) infectivity than other collectins. We now show that recombinant conglutinin and a chimeric protein containing the NH2terminus and collagen domain of rat pulmonary surfactant protein D (rSP-D) fused to the neck region and carbohydrate recognition domain (CRD) of conglutinin (termed SP-D/Congneck+CRD) have markedly greater ability to inhibit infectivity of IAV than wild-type recombinant rSP-D, confirming that the potent IAV-neutralizing activity of conglutinin resides in its neck region and CRD. Furthermore, by virtue of incorporation of the NH2terminus and collagen domain of SP-D, SP-D/Congneck+CRDcaused substantially greater aggregation of IAV particles and enhancement of neutrophil binding of, and H2O2responses to, IAV than recombinant conglutinin or recombinant rSP-D. Hence, SP-D/Congneck+CRDcombined favorable antiviral and opsonic properties of conglutinin and SP-D. This study demonstrates an association of specific structural domains of SP-D and conglutinin with specific functional properties and illustrates that antimicrobial activities of wild-type collectins can be enhanced through recombinant strategies.
Curosurf modulates cAMP accumulation in human monocytes through a membrane-controlled mechanism
Authors: Pinot Françoise , Walti Hervé , Haagsman Henk P. , Polla Barbara S. , Bachelet Maria
Published: December 2017

The cellular mechanisms by which pulmonary surfactant exerts its effects, including anti-inflammatory or proinflammatory effects, have remained elusive. To address the issue of whether plasma membrane modifications represent a target for these mechanisms, we designed an experimental protocol involving the determination of changes in cAMP levels under membrane-dependent or -independent stimulatory pathways. The effects of a modified natural porcine surfactant, Curosurf, and the major surfactant protein A were evaluated on resting and stimulated cAMP levels of human monocytes. We found that agents that elevate intracellular cAMP exhibit different susceptibilities toward a preexposure to Curosurf. The rise in cAMP induced by membrane-active agents such as cholera toxin or the diterpene forskolin was significantly inhibited by monocyte preexposure to Curosurf. In contrast, the rise in cAMP induced by the membrane-permeant phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine or by the Bordetella pertussis toxin adenylate cyclase-hemolysin was unaffected by Curosurf. Surfactant protein A did not affect either cAMP levels or the inhibitory capacity of Curosurf. We suggest that a plasma membrane-associated event affecting the mechanism underlying the effects of cholera toxin or forskolin is involved in the inhibition of cAMP accumulation caused by Curosurf.
Mechanisms of increased Na+transport in ATII cells by cAMP: we agree to disagree and do more experiments
Authors: Lazrak Ahmed , Nielsen Vance G. , Matalon Sadis
Published: December 2017

Existing evidence supports the presence of active transport of Na+across the mammalian alveolar epithelium and its upregulation by agents that increase cytoplasmic cAMP levels. However, there is controversy regarding the mechanisms responsible for this upregulation. Herein we present the results of various patch-clamp studies indicating the presence of 25- to 27-pS, amiloride-sensitive, moderately selective Na+channels (Na+-to-K+permeability ratio = 7:1) located on the apical membranes of rat alveolar type II (ATII) cells maintained in primary culture. The addition of terbutaline to the bath solution increased the open probability of single channels present in cell-attached patches of ATII cells without affecting their conductance. A similar increase in open probability was seen after the addition of protein kinase A, ATP, and Mg2+to the cytoplasmic side of inside-out patches. Measurement of short-circuit currents across confluent monolayers of rat or rabbit ATII cells indicates that terbutaline and 8-(4-chlorophenylthio)-cAMP increase vectorial Na+transport and activate Cl−channels. Currently, there is a controversy as to whether the cAMP-induced increase in Na+transport is due solely to hyperpolarization of the cytoplasmic side of the ATII cell membrane due to Cl−influx or whether it results from simultaneous stimulation of both Cl−and Na+conductive pathways. Additional studies are needed to resolve this issue.