bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of rate and rhythm on contraction of rat papillary muscle
Authors: Hoffman Brian F. , Kelly John J.
Published: December 2017

The unusual relationship between frequency of contraction and tension developed by the isolated rat papillary muscle has been studied in detail. The progressive decrease in tension with increasing rate is unrelated to the size or weight of the muscle and is not changed by alterations in the ionic composition of the perfusion medium. The force-frequency relationship is also unchanged by addition of plasma, epinephrine or digitalis to the perfusion medium. Rat papillary muscle is similar to other preparations of cardiac muscle with respect to recovery of contractility and the development of rest contractions and postextrasystolic potentiation.
Resistance to whole-body X-irradiation in rats made tolerant to bacterial endotoxins
Authors: Zweifach B. W. , Kivy-Rosenberg E. , Nagler Arnold L.
Published: December 2017

Rats were treated with three conditioning agents (bacterial endotoxins, zymosan and compound 48/80) known to produce tolerance to other forms of stress, as a means of determining the importance of the reticulo-endothelial system in the response to WBR. Effective protection was provided by tolerance induced by lipopolysaccharide extracts of E. coli bacteria. Some protection was also afforded by conditioning with 48/80 for several days. These agents were active only when administered before exposure to x-rays. Treatment post x-ray broke down the induced resistance. Blood platelet levels remained high in conditioned animals exposed to WBR. It is suggested that a relationship exists between the priming or conditioning of the reticuloendothelial system and the maintenance of satisfactory blood platelet levels in adapted animals receiving WBR.
Activity of the cardiac pacemaker of the frog in relation to atrial fibrillation and to other atrial arrhythmias
Authors: Nelson J. Roger , Smith John R.
Published: December 2017

Observations of the activity of the sinus venosus of the frog heart indicate that function of the sinus is regular and sustained during suppression of the atria and ventricle by optimum amounts of acetylcholine. When atrial fibrillation was induced by acetylcholine injection and concurrent atrial distention, the sinus venosus also beat regularly and independently, neither affecting nor being affected by the adjacent fibrillating atria. In a number of observations, sinus impulses appeared to initiate momentary fibrillation in localized atrial areas, leading eventually to perpetual fibrillation of the atria. Furthermore, in occasional hearts, regularly occurring waves of atrial transmission passed through the sino-atrial junction to invoke sinus contractions in regularity with the ectopic focus. These phenomena may be related to the sino-atrial junctional tissue, which prevents transgression of impulses from the fibrillating atria so that sinus rhythm is preserved; however, under certain conditions, the junctional zone will permit impulses to pass from atrium to sinus venosus as an A-S sequence.
Active transport of Fe59 by everted segments of rat duodenum
Authors: Dowdle Eugene B. , Schachter David , Schenker Harris
Published: December 2017

Everted gut sacs prepared from segments of the proximal small intestine of rats transport Fe59 from the mucosal to the serosal surfaces against concentration gradients in vitro. The active transport mechanism is dependent upon oxidative metabolism and the generation of phosphate-bond energy, and is limited in capacity. The active transport process is maximal in the region of the small intestine immediately distal to the pylorus and diminishes with more distal segments of the gut. Addition of ascorbic acid to the incubation medium markedly increases the active transport of Fe59 in vitro.
Effect of prolonged cold exposure on components of the electron transport system
Authors: Hannon John P.
Published: December 2017

The effect of 3–4 weeks exposure to 5° ± 1°C on the activity of enzymes associated with the electron transport system of rat liver and gastrocnemius muscle was investigated. The enzymes included lactic, succinic and malic dehydrogenase, DPNH-cytochrome c reductase and cytochrome oxidase. Cold exposure led to increased activities on the part of succinic and malic dehydrogenase and cytochrome oxidase. Muscle tissue exhibited a greater response in these components than liver tissue. Lactic dehydrogenase and DPNH-cytochrome c reductase activities were unaffected by cold exposure in either liver or muscle. Thyroxine, 2,4-dinitrophenol, phosphate and hexokinase-glucose stimulated the activity of succinic dehydrogenase activities of liver tissue, with hexokinase-glucose producing the greatest effect. The degree of stimulation by these agents was the same, however, for tissue from cold exposed animals as it was for controls. It was concluded that the increased tissue oxygen consumption in the cold-acclimatized rat was attributable to at least three mechanisms: a) an increased enzyme concentrations; b) a stimulation of latent enzyme activity; and c) an uncoupling of oxidative phosphorylation.
Production and life span of erythrocytes during hibernation in the golden hamster
Authors: Brock Mary Anne
Published: December 2017

One day following radioiron injection, the concentration of the isotope in erythrocytes of control hamsters was 14.1 times the concentration in hibernators' erythrocytes during the 2nd day of hibernation. During this same period, hibernators' plasma contained 4.62 times the control concentration of radioiron. At definite times after tagging, activity of chromium 51-labeled erythrocytes was measured in warm and cold-exposed animals and in hamsters after measured periods of hibernation. In the active animals, the potential erythrocyte half-life was approximately 40 days; the effective half-life was about 15 days. Retardation of senescence and the virtual absence of random destruction in erythrocytes of hibernating hamsters increased the potential erythrocyte life to approximately 160 days. Both the minimal metabolic activity of the animal and the retardation of intrinsic senescent processes in erythrocytes were considered to be responsible for the diminished erythropoietic stimulus in hibernating hamsters. Radioiron transport across the cell membrane, its incorporation into hemoglobin, and mitotic activity of marrow erythroid elements were component processes of erythropoiesis which were probably retarded.
Effect of brain-stem stimulation on renal function
Authors: Wise Burton L. , Ganong William F.
Published: December 2017

The effect of stimulation of the hypothalamus, midbrain, pons and medulla oblongata on renal excretion of water, sodium and potassium and on glomerular filtration rate has been determined in 26 pentobarbital anesthetized dogs with chronically implanted electrodes. The effect of renal denervation on the stimulation responses has been determined in 12 animals. Stimulation of 15 points in the dorsal medulla just lateral to the mid-line led to a rise in blood pressure and an associated fall in creatinine clearance and urine volume. The renal changes were blocked by renal denervation. Stimulation of six points located in and near the area postrema led to a rise in creatinine clearance and urine volume without a significant change in systemic blood pressure. Stimulation of two points in the pons led to increases in sodium excretion without a detectable change in glomerular filtration rate. Stimulation of three points in the midbrain led to a decrease in creatinine clearance, but stimulation of 39 points elsewhere in the medulla, pons, midbrain and posterior hypothalamus had no effect on glomerular filtration rate and water and electrolyte excretion, even though changes in blood pressure did occur with some of these stimuli.
Contour changes of the aortic pulse during propagation
Authors: Remington John W.
Published: December 2017

Changes in aortic pulse contour were mapped by moving a recording sound through the aorta of lightly anesthetized dogs. The initial anacrotic slope of the ascending aortic (root) pulse usually traverses the arch and the thoracic aorta unchanged, but is often steepened in the abdominal aorta. The break in this slope occurs at a progressively higher pressure level as the pulse moves outward. Starting in the descending arch, a new wave, not seen in the root pulse, rises from the broad top of the systolic portion of the pulse. As the pulse moves peripherad, the peak of this wave moves progressively earlier until finally it may merge with the anacrotic slope itself. Hence the peaks are approximately simultaneous for all parts of the aorta beyond the arch, i.e. they are ‘standing waves.’ In a few cases, the root pulse shows a small but clear negative trough coincident with this peripheral pulse peak. In late systole or early diastole, the root pulse shows a pressure plateau or even a rise, while the pressure in the peripheral pulses is falling sharply to make a trough. Following this, there may be one or more reciprocal oscillations between the root and a peripheral aortic pulse. While standing waves are commonly seen in the dog, they are not developed in some cases, but the pulse pressure may still show an augmentation.
Hepatic uptake and biliary excretion of Indocyanine green and its use in estimation of hepatic blood flow in dogs
Authors: Ketterer Sigmund G. , Wiegand Bernard D. , Rapaport Elliot
Published: December 2017

Indocyanine green when injected intravenously into normal dogs rapidly disappears, after mixing, from the circulation in an initial exponential fashion. This property enables one to calculate its original volume of distribution and its clearance from the circulation. The initial volume of distribution corresponded closely with the circulating plasma volume. Recovery of the dye from surgically created biliary fistulas approached 100% of the injected amounts and averaged 91%. During constant infusion, significant hepatic arteriovenous differences in dye concentrations occurred, making it possible to calculate hepatic clearances, extraction ratios and liver blood flow. The values obtained by the latter method agreed well with those obtained following single injections. The virtually complete hepatic uptake of Indocyanine green, ease of quantitative plasma and biliary determinations and its exponential loss from the circulation with a short half-life provide advantages over previously used substances in evaluating hepatic function and blood flow.
Rhythm effects on contractility of the beating isovolumic left ventricle
Authors: Lendrum B. , Feinberg H. , Boyd E. , Katz L. N.
Published: December 2017

Variation in contractile force of the isovolumic contracting left ventricle of the dog was studied in open-chested in situ hearts. The electrocardiogram and intraventricular pressures were recorded at various heart volumes. Spontaneous changes in heart rate and rhythm occurred at all volumes. Isovolumic systolic pressure development (contractile force) varied with rate and rhythm. Contractile force increased with heart rate (treppe) regardless of pacemaker origin. When a premature beat was followed by a compensatory pause, the premature beat showed a decrease and the next beat an increase in contractile force (postextrasystolic potentiation). The magnitude of the changes varied directly with the prematurity of the beat. Mechanical alternans was observed with electrical alternans, despite the absence of significant volume change. Rate-induced changes, postextrasystolic potentiation and mechanical alternans were additive when they occurred simultaneously. For practical purposes, ventricular volume (filling), hence muscle fiber length, remained constant during these rate and rhythm change, therefore could not affect the strength of contraction. Contractile force changes directly attributable to rate and rhythm changes do, therefore, occur in the intact mammalian heart.
Changes in tissue pH after circulatory arrest
Authors: Crowell Jack W. , Kaufmann Berwind N.
Published: December 2017

The circulation of dogs was stopped by fibrillation of the heart, and needle pH electrodes were placed in various tissues of dogs. The pH electrodes were connected to a continuous recording pH meter and the pH of the tissues was measured for a period of 1 hour following circulatory arrest. A few incidental studies on metabolic inhibitors, hypothermia and alkalinizing agents were made in addition to studies on the normal animals. It was found that the initial pH in the normal animals was 7.2–7.3, but within a short period of time decreased to values lethal to an animal with a normal circulation. The cerebral cortex showed the most rapid decrease in pH following circulatory arrest. The injection of sodium bicarbonate before circulatory arrest was of little value in preventing the development of acidity. Oxythiamine was effective in preventing the development of severe acidity but appears of little practical use. Hypothermia to 25°C proved effective in retarding the development of severe acidity in the two animals studied.
Alterations in feeding and drinking behavior of rats with lesions in globi pallidi
Authors: Morgane P. J.
Published: December 2017

Stereotaxic lesions were placed in several parasagittal planes of the lateral hypothalamus of rats at the level of the ventromedial nuclei. Both far- and mid-laterally lesioned animals developed adipsia and aphagia, with the far-lateral syndrome being more drastic in nature. The qualitatively different nature of the "failures" seen between the two groups correlated well with the additional damage to the pallidofugal fiber systems in the far-lateral lesioned group. Bilateral lesions directed to the origins of the pallidofugal fibers reproduced faithfully the far-lateral hypothalamic syndrome, histological studies in these animals revealing degeneration along the pallidofugal trajectories. It appears that the feeding and/or drinking "centers" are only convergence sites for critical fiber systems which are disjoined by far-lateral hypothalamic lesions. Thus, the medial part of the "feeding center" seems to be primarily a "motivational" system, whereas the lateral "feeding" system is more basic and depends essentially on pallidofugal circuitry. When this latter is disjoined, the failure is more than "motivational," since it is not compensated for by merely delivering food and water to the gastrointestinal tract.
Determining thresholds of aversive brain stimulation
Authors: Boren John J. , Malis Jerry L.
Published: December 2017

This study describes a method for determining thresholds of aversive brain stimulation. Chronically indwelling electrodes were implanted in selected brain areas of monkeys, who were then trained to press a lever in order to reduce the electric current stimulating these areas. In the absence of a response, the current rose in small steps until responding, which decreased the current in steps, was again initiated. Following the demonstration of rather precise, immediate control of lever pressing by the brain stimulation, variables affecting magnitude and variability of the threshold were explored. It was found that an increase in size of the current steps increased peak current levels and width of the oscillations. Using a variation of the technique where responding terminated brain stimulation (rather than reducing it in steps), it was shown that increasing the number of responses required for termination elevated threshold and lowered variability. An analgesic drug, anileridine, caused a threshold rise with larger doses having greater effects. In an experiment where maximum current was selectively limited, it was found that current levels the animal would tolerate continuously were levels that normally evoked responding. These data were interpreted as indicating that behavioral control by brain stimulation is complicated by discriminated avoidance behavior with lower current levels functioning as warning stimuli.
Effects of denervation and vasoactive agents on vascular pressures and weight of dog forelimb
Authors: Haddy Francis J. , Molnar Joyce I. , Campbell Richard W.
Published: December 2017

The dog forelimb was locally denervated and vasoactive agents infused into the brachial artery at rates having little effect upon large vessel pressures. Forelimb weight and small and large arterial and venous pressures were frequently recorded. Because the limb was in a dependent position, it gained weight at a diminishing rate. Denervation increased small venous pressure and the rate of weight gain. Angiotensin and vasopressin decreased small venous pressure and the rate of weight gain. Methacholine, serotonin and histamine each increased small venous pressure and the rate of weight gain. Levarterenol decreased, did not change or increased, both small venous pressure and rate of weight gain. These findings, when combined with previously reported effects upon arterial and venous resistances, indicate that local denervation and local administration of vasoactive agents vary the transfer of water across the capillary membrane by changing capillary hydrostatic pressure and emphasize the importance of the ratio of arterial to venous resistances in determining capillary hydrostatic pressure and, hence, water storage in tissues.
Functions of separate sensory receptors of nonauditory labyrinth of the cat
Authors: Money Kenneth E. , Scott John W.
Published: December 2017

A technique for plugging individual semicircular canals of cats was developed, and it was established that the plugging of a semicircular canal completely blocked its receptivity without influencing the functions of the other vestibular receptors. It was found that cats with all six semicircular canals plugged were lacking all sensitivity to angular acceleration, but they retained normal responses to linear acceleration. Results of several vestibular tests led to the conclusion that the vertical semicircular canals initiate corrections for fast angular displacements from the normal orientation when the displacements are about horizontal axes and that the otoliths initiate corrections for slow angular displacements about horizontal axes. In tests of single horizontal canals, the durations of postrotatory nystagmus were the same after rotations in opposite directions. It was concluded that in the intact animal both horizontal semicircular canals contribute equally to reception of angular acceleration in both directions.
Active transport of iron by intestine: features of the two-step mechanism
Authors: Manis James G. , Schachter David
Published: December 2017

Everted gut sacs prepared from the proximal duodenum of the rat, mouse, and golden hamster can transfer iron actively, i.e. against concentration and potential gradients, from the mucosa to the serosa. The active transfer involves two steps: mucosal uptake and net transfer to the serosal surface. Oxidative metabolism is apparently required for each of the steps. Net transfer to the serosal surface is slower, more readily rate-limited, and more sharply localized to the proximal duodenum than is mucosal uptake. Both divalent and trivalent iron are taken up at the mucosal surface, but net transfer to the serosal surface is relatively specific for divalent iron. Calcium inhibits the net serosal transfer of iron at concentrations which do not inhibit the mucosal uptake. Parallel studies with loops of duodenum in living rats indicate that the active, two-step mechanism for iron absorption also functions in vivo, where the steps in the transfer are mucosal uptake followed by transport from the tissue to the blood stream.
Oxygen consumption and active transport in separated renal tubules
Authors: Burg Maurice B. , Orloff Jack
Published: December 2017

A method for the separation of intact viable cells from rabbit renal cortex has been developed. Separation is achieved by treatment of the excised kidney with the proteolytic enzyme collagenase. The resultant suspension consists principally of short lengths of proximal tubules. Survival of the tissues is indicated by maintenance of oxygen consumption, PAH uptake, and electrolyte composition. Since, in contrast to renal cortical slices, the cells in the tubule suspension are bathed directly by a solution of uniform composition, there is more rapid accumulation of PAH and a higher rate of oxygen consumption in this preparation than in slices. The technique affords a method for the direct measurement of fluxes across membranes of kidney cells.
Decreased spontaneous locomotor activity in the rat induced by hypothalamic lesions
Authors: Gladfelter W. E. , Brobeck John R.
Published: December 2017

A permanent decrease in spontaneous locomotor activity of the rat can be produced by destruction of either of two specific regions in the ventral hypothalamus at the level of the tuber cinereum. One is a lateral region which lies between the fornix and cerebral peduncle and extends from the level of the fornix downward to the base of the brain. Its rostrocaudal extent seems to be from about the level of the posterior border of the paraventricular nucleus back to, but not including, the premammillary area. The other is a medial region which seems to lie adjacent to the ventral half of the third ventricle, extending laterally from this structure only about .5–1 mm. This region, too, appears to reach to the base of the brain. The exact rostrocaudal extent of this medial region is uncertain, but at least it does not extend rostrally into the preoptic area nor caudally into the premammillary area. Activity was decreased to a much lower level after lateral lesions than after medial lesions. Lesions in other parts of the hypothalamus did not produce hypoactivity. Hypoactivity seemed to occur independently of other signs of hypothalamic impairment.
Venous response of intestine to endotoxin
Authors: Hinshaw Lerner B. , Nelson David L.
Published: December 2017

Extensive congestion of the splanchnic bed has been observed in the dog after lethal injections of endotoxin. The purpose of this investigation was to determine the role of small mesenteric veins in the development of visceral pooling; isolated sections of small intestines were removed from dogs and continuously perfused with blood obtained from intact dogs administered lethal injections of E. coli endotoxin. Results show significant mesenteric venous responses to blood-borne agents. Increases in venous segment resistance and intestine weight were found during the postendotoxin period. Evidence indicates that the progressive development of splanchnic pooling is primarily due to active constriction of small veins in which responsiveness to epinephrine is enhanced by endotoxin.
Red cell life span in the turtle and toad
Authors: Altland Paul D. , Brace Kirkland C.
Published: December 2017

Estimates of the mean life span of the red blood cells of box turtles and South American giant toads were made with glycine-2-C14. The mean life span of the turtle red cells probably lies between 600 and 800 days and that of the toad between 700 and 1,400 days. The body weight, hematocrit, and hemoglobin values remained at relatively normal levels for 7 years in turtles and nearly 2 years in toads. These results indicate that the low metabolic rate, characteristic of poikilotherms, is correlated with a long red cell life span.
Excitation of rat urinary bladder by coaxial electrodes and by chemical agents
Authors: Carpenter F. G.
Published: December 2017

Electrical stimulation of an isolated rat urinary bladder in tris buffered Ringer's solution by coaxial electrodes elicits contractile responses amounting to 70–130 cm of water pressure. If the Ringer's solution is replaced by isotonic K2SO4 solution, pressures of 60–110 cm water pressure are developed. Responses elicited by low stimulating frequencies (.5–2.5/sec) and by K2SO4 are potentiated by physostigmine, however, 2 mg/liter atropine throughout the entire frequency range of .5–10/sec is without effect. The stimulating actions of K2SO4 and electrical stimuli are dependent upon the availability of Ca++. Responses to electric stimuli are believed to be mediated by way of cholinergic neural elements, those from K+ by a depolarization of the muscle fibers. To a more limited extent the contractile responses resulting from acetylcholine (ACh) are dependent upon Ca++ and contractures are also produced by ACh in bladders suspended in isotonic K2SO4. Conversely, electrical pulses or K2SO4 are effective stimuli in the presence of quantities of ACh or carbamylcholine sufficient to produce maximal responses. This suggests a different site of action for exogenous ACh as opposed to endogenous mediator released from cholinergic motor nerve terminals during motor nerve stimulation.
Perfusion of rat adipose tissue
Authors: Robert André , Scow Robert O.
Published: December 2017

A technique is described for perfusing the parametrial fat pad of the rat. The rate of flow through the tissue was dependent on temperature, pressure, and the protein composition of the perfusing fluid. The latter also had a pronounced effect on the rate of edema formation in the tissue. The rate of fatty acid release by perfused adipose tissue was affected by the nutritional state of the fat donor and by the composition of the perfusing fluid. Tissue from fed rats did not release fatty acids. Adipose tissue from fasted rats released fatty acids when the tissue was perfused with diluted blood (1.10) or 4% albumin solution but not when perfused with 8% albumin. Perfused tissue released fatty acids at a much faster rate than did incubated tissue. Diluted blood and serum inhibited the release of fatty acids by incubated adipose tissue.
Familial hypothalamic diabetes insipidus in rats (Brattleboro strain)
Authors: Valtin H. , Schroeder H. A.
Published: December 2017

Familial hypothalamic diabetes insipidus ( DI) has arisen as an apparently spontaneous mutation from a strain of Long-Evans hooded rats being bred for unrelated researches not involving radioactivity. The DI rats decrease water intake and urine flow, and increase urine osmolality in response to injected vasopressin. They concentrate their urines only minimally or not at all in response to dehydration, hypertonic saline, nicotine, or stress, and their serum osmolalities and sodium concentrations are significantly higher than those of normal animals. They show marked diminution of neurosecretory material in the neurohypophysis and supraoptic nucleus. The data suggest that the deficiency causing DI in these rats is a lack or dearth of synthesis of vasopressin or its carrier protein, or both.
Na-K activated adenosine triphosphatase formation of cerebrospinal fluid in the cat
Authors: Vates Thomas S. , Bonting Sjoerd L. , Oppelt W. Walter
Published: December 2017

Digitalis-sensitive Na-K activated ATPase (Na-K ATPase), implicated in active cation transport, was shown to occur in cat choroid plexus. Cerebrospinal fluid (CSF) formation rate, measured by collection from cat cerebral aqueduct was inhibited 18% by intravenous desacetyl lanatoside C (0.2 mg/kg). Ouabain, placed intraventricularly, caused inhibition of flow, ranging from 100% by 10–5 mole to 0% by 5 x 10–10 mole. After 10–6 mole ouabain, Na-K ATPase activity in lateral ventricle choroid plexus was inhibited 69% without change in digitalis-insensitive, Mg activated ATPase and carbonic anhydrase activities. Ventriculocisternal perfusion with varying concentrations of ouabain, scillaren A, and hexahydroscillaren A gave CSF flow inhibition (inulin dilution technique) correlating quantitatively with in vitro Na-K ATPase inhibition. Other compounds studied were erythrophleine, cassaine, and l-norepinephrine. It is concluded that the choroid plexus Na-K ATPase system has a primary function in the formation of CSF in the cat, presumably through the active secretion of Na ions into the ventricle.
Central modulation of the NO/cGMP pathway affects the MPOA-induced intracavernous pressure response
Authors: Sato Yoshikazu , Zhao Weixin , Christ George J.
Published: December 2017

Alterations in the nitric oxide (NO)/cGMP levels in hypothalamic nuclei, including the medial preoptic area (MPOA), regulate critical aspects of sexual behavior and penile reflexes. However, the effects of altered central nervous system (CNS) NO/cGMP levels at the end organ level, that is, on the magnitude/quality of the erection so achieved [intracavernous pressure (ICP) response], has yet to be evaluated. The goal of this report was to evaluate the effects of intrathecal administration of modulators of NO and cGMP levels on ICP responses to stimulation of the MPOA and cavernous nerve in rats in vivo. In all cases, intrathecal administration of compounds that increase and decrease cGMP and NO levels, respectively, was associated with corresponding increases and decreases in the MPOA-stimulated ICP response. Specifically, sodium nitroprusside (SNP), 8-bromo-cGMP, and sildenafil increased the MPOA-stimulated ICP response, whereas Nω-nitro-l-arginine methyl ester reduced it. None of the intrathecal treatments had detectable effects on blood pressure or the cavernous nerve-stimulated ICP response, although intravenous sildenafil increased the latter. These data clearly indicate that intrathecal drug administration affects central and not peripheral neural mechanisms and, moreover, documents that CNS NO/cGMP levels can affect erectile capacity per se (i.e., ICP) in the rat model.
Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress
Authors: Aoki Ken , Stephens Dan P. , Johnson John M.
Published: December 2017

It is not clear whether the diurnal variation in the cutaneous circulatory response to heat stress is via the noradrenergic vasoconstrictor system or the nonadrenergic active vasodilator system. We conducted whole body heating experiments in eight male subjects at 0630 (AM) and 1630 (PM). Skin blood flow was monitored by laser-Doppler flowmetry at control sites and at sites pretreated with bretylium (BT) to block noradrenergic vasoconstriction. Noninvasive blood pressure was used to calculate cutaneous vascular conductance. The sublingual temperature (Tor) threshold for cutaneous vasodilation was significantly higher in PM at control and at BT-treated sites (both P < 0.01), suggesting the diurnal shift in threshold depends on the active vasodilator system. The slope of cutaneous vascular conductance as a percentage of its maximum with respect to Tor was significantly lower in AM at control sites only. Also, in the AM, the slope at control sites was significantly lower than that at BT-treated sites ( P < 0.05), suggesting that the diurnal change in the sensitivity of cutaneous vasodilation depends on vasoconstrictor system function. Overall, the diurnal variation in the reflex control of skin blood flow during heat stress involves both vasoconstrictor and active vasodilator systems.
Effects of catecholamines on the pulmonary circulation in the ovine fetus
Authors: Jaillard S. , Houfflin-Debarge V. , Riou Y. , Rakza T. , Klosowski S. , Lequien P. , Storme L.
Published: December 2017

High levels of circulating catecholamines are found in the fetus, and fetal stress and birth induce a marked surge in catecholamine secretion. Little is known about the role of catecholamines on the fetal pulmonary circulation. To determine the effects of catecholamines on the pulmonary vascular tone, we tested the hemodynamic response to norepinephrine and dopamine infusion in chronically prepared late-gestation fetal lambs. We found that norepinephrine infusion (0.5 μg · kg−1· min−1) increased pulmonary artery pressure (PAP) by 10 ± 1% ( P < 0.01), left pulmonary artery blood flow by 73 ± 14% ( P < 0.01), and decreased pulmonary vascular resistance (PVR) by 33 ± 6% ( P < 0.01). The pulmonary vasodilator effect of norepinephrine was abolished after nitric oxide synthase inhibition. Dopamine infusion at 5 μg · kg−1· min−1did not significantly change PVR. Conversely, dopamine infusion at 10 μg · kg−1· min−1increased PAP ( P < 0.01) and progressively increased PVR by 30 ± 14% ( P < 0.01). These results indicate that catecholamines may modulate basal pulmonary vascular tone in the ovine fetus. We speculate that catecholamines may play a significant role in the maintenance of the fetal pulmonary circulation and in mediating changes in the transitional pulmonary circulation.
Synaptic plasticity in sympathetic ganglia from acquired and inherited forms of ouabain-dependent hypertension
Authors: Aileru Azeez A. , De Albuquerque Aline , Hamlyn John M. , Manunta Paolo , Shah Jui R. , Hamilton Matthew J. , Weinreich Daniel
Published: December 2017

Altered sympathetic nervous system activity has been implicated often in hypertension. We examined short-term potentiation [posttetanic potentiation (PTP)] and long-term potentiation (LTP) in the isolated superior cervical ganglia (SCG) from Sprague-Dawley (SD) rats given vehicle, digoxin, or ouabain by subcutaneous implants as well as in animals with ouabain-induced hypertension (OHR), and inbred Baltimore ouabain-resistant (BOR) and Baltimore ouabain-sensitive (BOS) strains of rats. Postganglionic compound action potentials (CAP) were used to determine PTP and LTP following a tetanic stimulus (20 Hz, 20 s). Baseline CAP magnitude was greater in ganglia from OHR than in vehicle-treated SD rats before tetanus, but the decay time constant of PTP was significantly decreased in OHR and in rats infused with digoxin that were normotensive. In hypertensive BOS and OHR, the time constants for the decay of both PTP and LTP ( t L) were increased and correlated with blood pressure (slope = 0.15 min/mmHg, r = 0.52, P < 0.047 and 6.7 min/mmHg, r = 0.906, P < 0.0001, respectively). In BOS and OHR, t L (minutes) was 492 ± 40 ( n = 7) and 539 ± 41 ( n = 5), respectively, and differed ( P < 0.05) from BOR (257 ± 48, n = 4), SD vehicle rats (240 ± 18, n = 4), and captopril-treated OHR (370 ± 52, n = 5). After the tetanus, the CAP at 90 min in BOS and OHR SCG declined less rapidly vs. SD vehicle rats or BOR. Captopril normalized blood pressure and t L in OHR. We conclude that the duration of ganglionic LTP and blood pressure are tightly linked in ouabain-dependent hypertension. Our results favor the possibility that enhanced duration of LTP in sympathetic neurons contributes to the increase in sympathetic nerve activity in ouabain-dependent hypertension and suggest that a captopril-sensitive step mediates the link of ouabain with LTP.
PYY inhibits CCK-stimulated pancreatic secretion through the area postrema in unanesthetized rats
Authors: Deng Xiaoying , Guarita Dulce R. , Pedroso Martha R. A. , Kreiss Christianna , Wood Paul G. , Sved Alan F. , Whitcomb David C.
Published: December 2017

Peptide YY (PYY) inhibits CCK-8-secretin-stimulated pancreatic secretion in vivo. To investigate whether CCK-8-secretin-stimulated pancreatic secretion is mediated through a vago-vagal pathway and whether PYY inhibits this pathway through the area postrema (AP), chronic pancreatic, biliary, and duodenal catheters were implanted in AP-lesioned (APX) or sham-operated rats. The effects of APX on pancreatic secretion stimulated by bethanechol, pancreatic juice diversion (PJD), or CCK-8-secretin, were tested, with and without background PYY infusion, in unanesthetized rats. APX reduced basal pancreatic secretion by 15–20% ( P < 0.01). APX had no effect on bethanechol-stimulated secretion and potentiated protein secretion stimulated by PJD (396 vs. 284%) and exogenous CCK-8-secretin. In sham-operated rats, background PYY potently inhibited CCK-8-secretin-stimulated pancreatic fluid (1.8 vs. 48.2%) and protein secretion (3.7 vs. 45.8%) but potentiated fluid (52.9 vs. 43.1%) and protein (132.9 vs. 68.9%) secretion in APX rats. Our findings demonstrate that PYY inhibits CCK-8-secretin-stimulated pancreatic secretion through an AP-dependent mechanism in sham-operated rats. The AP also contributes to basal pancreatic secretion.
Predicting cerebral blood flow response to orthostatic stress from resting dynamics: effects of healthy aging
Authors: Narayanan K. , Collins James J. , Hamner Jason , Mukai Seiji , Lipsitz Lewis A.
Published: December 2017

The transfer function relating arterial pressure (AP) to cerebral blood flow velocity (CBFV) during resting conditions has been used to predict the CBFV response to hypotension. We hypothesized that this approach could predict the CBFV response to posture change in elderly individuals if impaired autoregulation allowed changes in AP to be passively transferred to CBFV. AP (Finapres) and CBFV (middle cerebral artery transcranial Doppler) were measured in 10 healthy young (age 24 ± 1 yr) and 10 healthy elderly (age 72 ± 3 yr) subjects during 5 min of quiet sitting and 1 min of active standing while breathing was paced at 0.25 Hz. Transfer functions between AP and CBFV changes during sitting were estimated from each full waveform in both low-frequency (LF; 0.05–0.2 Hz) and heartbeat-frequency (HBF; 0.7–1.4 Hz) ranges. The impulse-response function was used to compute changes in CBFV during posture change. The LF transfer function did not predict orthostatic changes in CBFV in either group, suggesting normal cerebral autoregulation. In the HBF range, the prediction was high in elderly ( R = 0.65 ± 0.23) but not young subjects ( R = 0.19 ± 0.35; P < 0.003, young vs. elderly). Thus rapidly acting regulatory mechanisms that reduce the transmission of beat-to-beat changes in AP to CBFV may be engaged during posture change in young but not elderly subjects.
Circulating angiotensin II mediates sodium appetite in adrenalectomized rats
Authors: Schoorlemmer G. H. M. , Johnson A. K. , Thunhorst R. L.
Published: December 2017

We investigated the role of circulating ANG II in sodium appetite after adrenalectomy. Adrenalectomized rats deprived of their main access to sodium (0.3 M NaCl) for 9 h drank 14.1 ± 1.5 ml of the concentrated saline solution in 2 h of access. Intravenous infusion of captopril (2.5 mg/h) during the last 5 h of sodium restriction reduced sodium intake by 77 ± 12% ( n = 5) without affecting the degree of sodium depletion and hypovolemia incurred during deprivation. Functional evidence indicates that this dose of captopril blocked production of ANG II in the peripheral circulation, but not in the brain; that is, injection of ANG I into the lateral brain ventricle stimulated intake of both water and 0.3 M NaCl. Intravenous infusion of ANG II (starting 10–15 min before 0.3 M NaCl became available) in adrenalectomized, captopril-treated rats restored both sodium intake and blood pressure to values seen in rats not treated with captopril. Longer (20 h) infusions of captopril in 22-h sodium-restricted rats also blocked sodium appetite, but reduced or prevented sodium depletion. Intravenous infusion of ANG II after these long captopril infusions stimulated sodium intake, but intake was less than in controls not treated with captopril. These results indicate that most or all of the sodium appetite of adrenalectomized rats is mediated by circulating ANG II.
Amylin infusion into rat nucleus accumbens potently depresses motor activity and ingestive behavior
Authors: Baldo Brian A. , Kelley Ann E.
Published: December 2017

Amylin, a calcitonin gene-related peptide-like peptide coreleased with insulin, exerts anorexic effects on central administration. Because previous studies revealed dense amylin binding in the nucleus accumbens (Acb), we investigated the behavioral effects of amylin infusions (10, 30, and 100 ng/side) into Acb subregions. Intra-Acb shell amylin infusions decreased ambulation, rearing, feeding, and drinking in either food-deprived rats or water-deprived rats; motor activity was affected more potently than ingestive behavior. Moreover, intra-Acb shell amylin reduced motor activity in nondeprived rats tested in the absence of food or water, indicating that the expression of amylin's effects is independent of drive or proximal incentives. Intra-Acb core amylin infusions in water-deprived rats also decreased ambulation and water intake, although anterior Acb placements were associated with smaller motor effects, regardless of Acb subregion. In contrast to amylin's effects, intra-Acb shell infusions of orexin-A (50, 100, and 500 ng/side) had no effects on motor activity, feeding, or drinking. Hence the Acb may be a target for behavioral regulation by satiety-related peptides like amylin.
Effects of chronic cardiac decentralization on functional properties of canine intracardiac neurons in vitro
Authors: Smith F. M. , McGuirt A. S. , Leger J. , Armour J. A. , Ardell J. L.
Published: December 2017

Although intrinsic cardiac neurons display ongoing activity after chronic interruption of extrinsic autonomic inputs to the heart, the effects of decentralization on individual neurons remain unknown. The objective of this study was to determine the effects of chronic (3–4 wk) surgical decentralization on intracellular properties of, and neurotransmission among, neurons contained within the canine intrinsic right atrial ganglionated plexus in vitro. Properties of neurons from decentralized hearts were compared with those of neurons from sham-operated hearts (controls). Two populations of neurons were identified by their firing behavior in response to intracellular current injection. Fifty-nine percent of control neurons and 72% of decentralized neurons were phasic (discharged one action potential on excitation). Forty-one percent of control neurons and 27% of decentralized neurons were accommodating (multiple discharge with decrementing frequency). After chronic decentralization, input resistance of phasic neurons increased, whereas the duration of afterhyperpolarization of accommodating neurons decreased. Postsynaptic responses to interganglionic nerve stimulation were evoked in 89% of control neurons and 83% of decentralized neurons; the majority of these responses involved nicotinic receptors. These results show that, after chronic decentralization, intrinsic cardiac neurons 1) undergo changes in membrane properties that may lead to increased excitability while 2) maintaining synaptic neurotransmission within the intrinsic cardiac ganglionated plexus.
Muscle contractile properties during intermittent nontetanic stimulation in rat skeletal muscle
Authors: Verburg Esther , Thorud Hanne-Mari Schiøtz , Eriksen Morten , Vøllestad Nina K. , Sejersted Ole M.
Published: December 2017

To examine changes in contractile properties and mechanisms of fatigue during submaximal nontetanic skeletal muscle activity, in situ perfused soleus (60-min protocol) and extensor digitorum longus (EDL; 10-min protocol) muscles of the rat were electrically stimulated intermittently at low frequency. The partly fused trains of contractions showed a two-phase change in appearance. During the first phase, relaxation slowed, one-half relaxation time increased, and maximal relaxation first derivative of force (dF/d t) decreased. Developed force during the trains was reduced and was closely related to the rate of relaxation in this first phase. During the second phase, relaxation became faster again, one-half relaxation time decreased, and force returned to resting levels between contractions in a train. In contrast, developed force remained reduced, so that peak force of the contractions was 51% (soleus) and 30% (EDL) of control. In the soleus muscle, the changes in contractile properties were not related to ATP, creatine phosphate, or lactate content. The changes in contractile properties fit best with a mechanism of fatigue involving changes in Ca2+ handling by the sarcoplasmic reticulum.
Bioelectric properties and ion transport of excised rabbit trachea
Authors: Jarnigan F. , Davis J. D. , Bromberg P. A. , Gatzy J. T. , Boucher R. C.
Published: December 2017

Bioelectric properties and 22Na+ and 36Cl- isotopic flows across rabbit trachea, an airway epithelium without submucosal glands, were measured in vitro. One hundred twenty-two excised tracheas exhibited a mean transepithelial electric potential difference (PD) of 12 mV (lumen negative), a conductance (G) of 8.5 mS X cm-2, and a short-circuit current (Isc) of 90 microA X cm-2. G remained stable for more than 3 h, but Isc and PD fell slowly (10%/h). G was inversely correlated with PD, but Isc and G were not correlated. Na+ was absorbed under both open-circuit (1.7 mueq. cm-2 X h-1) and short-circuit (2.2 mueq X cm-2 X h-1) conditions. Net Na+ transport accounted for 70% of Isc of the short-circuited trachea. Net Cl- flow in the absorptive direction approximated that of Na+ under open-circuit conditions (1.6 mueq X cm-2 X h-1). Under short-circuit conditions the small net flow of Cl- in the direction of secretion (0.4 mueq X cm-2 X h-1) was not significant. Both unidirectional Cl- fluxes were correlated with G; [14C]-mannitol permeability and Na+ flows were weakly or not correlated with G. We found no evidence of net HCO-3 or proton transport. Acetylcholine (10(-4) M), phenylephrine (10(-5) M), or isoproterenol (10(-5) M) induced no change in bioelectric properties or ion flows. We conclude that the rabbit trachea is primarily a Na+ absorbing epithelium. The absence of a correlation between mannitol permeability and G suggests that much of the Cl- conductance is transcellular. Whereas insensitivity of rabbit trachea to cholinergic and alpha-adrenergic agents is compatible with the absence of glands, the lack of response to beta-adrenergic agonists denotes a species difference (compared with canine trachea) in airway-surface epithelial cell function.
Gate mechanism in breathlessness caused by chest wall vibration in humans
Authors: Homma I. , Obata T. , Sibuya M. , Uchida M.
Published: December 2017

The effects of bilateral alternating out-of-phase vibrations were studied in 10 normal healthy subjects and five asthmatic patients. The second or third intercostal spaces were vibrated during expiration, and the seventh to ninth intercostal spaces were vibrated during inspiration. Most subjects sensed breathlessness during such vibrations, and 100 Hz was most effective. The degree of breathlessness correlated positively with increased respiratory rate. Respiratory rate increased from 14.1 +/- 3.78 (mean +/- SD) to 22.3 +/- 7.14 breaths/min (P less than 0.05) during relatively severe breathlessness and to 20.39 +/- 5.66 breaths/min (P less than 0.05) during less uncomfortable sensation. Slight or negligible breathlessness induced no significant increase in rate (15.33 +/- 4.19 breaths/min). All asthma patients described the sensations during vibration as similar to those during asthma attacks, and their respiratory rates increased 20.7 +/- 11.03% during 100 Hz vibration (P less than 0.01). It is suggested that the uncomfortable sensation of breathlessness may be induced by muscle spindles in the intercostal muscles being activated out of phase with the respiratory cycle. The central mechanism that receives the intercostal afferents may have a certain gate that operates in relation to the sensation of breathlessness.
Influence of suspension hypokinesia on rat soleus muscle
Authors: Templeton G. H. , Padalino M. , Manton J. , Glasberg M. , Silver C. J. , Silver P. , DeMartino G. , Leconey T. , Klug G. , Hagler H. , et al.
Published: December 2017

Hindlimb hypokinesia was induced in rats by the Morey method to characterize the response of the soleus muscle. Rats suspended for 1–4 wk exhibited continuous and significant declines in soleus mass, function, and contractile duration. Soleus speeding was in part explained by an alteration in fiber type. The normal incidence of 70–90% type I fibers in the soleus muscle was reduced after 4 wk of suspension to 50% or less in 9 of 11 rats. A significant decline in type I myosin isozyme content occurred without a change in that of type II. Other observed histochemical changes were characteristic of denervation. Consistent with soleus atrophy, there was a significant increase in lysosomal (acid) protease activity. One week of recovery after a 2-wk suspension was characterized by a return to values not significantly different from control for muscle wet weights, peak contraction force, one-half relaxation time, and type I myosin. Persistent differences from control were observed in maximal rate of tension development, contraction time, and denervation-like changes.