bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between decreased splenic ATP levels and immunodepression: amelioration with ATP-MgCl2
Authors: Meldrum D. R. , Ayala A. , Wang P. , Ertel W. , Chaudry I. H.
Published: December 2017

Although it is known that decreased ATP levels in liver and kidney contribute to organ dysfunction after shock, it remains unknown whether there is any association between decreased splenocyte ATP levels and splenic immune functions. Moreover, although studies have shown that ATP-MgCl2 treatment after shock improves hepatic and renal ATP levels and organ function, it remains unknown whether splenocyte ATP levels and immune functions are similarly affected by this agent. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mmHg, maintained at that pressure for 60 min, resuscitated with shed blood and Ringer lactate, and treated with ATP-MgCl2 (80 mumol/kg) or vehicle (saline). Splenocytes (SPL) were harvested at various intervals after hemorrhage, ATP levels were assessed by 31P nuclear magnetic resonance spectrometry, and functions were determined by measuring proliferative capacity and interleukin (IL)-2, and IL-3 synthesis. Hemorrhage depleted SPL ATP levels to 1.7 +/- 0.8% of control levels. However, there was a significant increase in ATP levels of ATP-MgCl2-treated mice (77 +/- 11%, P less than 0.05) compared with vehicle-treated animals (13 +/- 4.1%) at 1 h after resuscitation. SPL ATP levels returned to control by 2 h after resuscitation in the ATP-MgCl2 group, whereas ATP levels of the vehicle-treated mice remained significantly depressed (P less than 0.05) for up to 12 h after resuscitation. At 1 h after resuscitation, SPL proliferative capacity and IL-2 and IL-3 synthesis were all profoundly depressed in the vehicle-treated group (P less than 0.05 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS)
Interaction of hypothalamic GABAA and excitatory amino acid receptors controlling heart rate in rats
Authors: Soltis R. P. , DiMicco J. A.
Published: December 2017

We have previously shown that microinjection of drugs that impair gamma-aminobutyric acid (GABA)-mediated synaptic inhibition into the dorsomedial hypothalamus (DMH) of rats generates cardiovascular and behavioral changes that mimic the response to stress. The purpose of this study was to examine the role of excitatory amino acid (EAA) receptors in the DMH in generating the cardiovascular changes caused by withdrawal of local GABAergic inhibition in urethan-anesthetized rats. Local treatment of the DMH with the nonselective EAA antagonist kynurenic acid blocked or reversed the increases in heart rate and blood pressure caused by microinjection of the GABAA antagonists bicuculline methiodide (BMI) or picrotoxin into the same region. Conversely, similar injection of xanthurenic acid, a structural analogue of kynurenic acid without significant effects on EAA receptors, did not significantly alter the cardiovascular changes produced by either GABAA antagonist. The tachycardic effects of BMI were also attenuated by injection of either the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanoic acid or the non-NMDA EAA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. When the two EAA receptor antagonists were combined, their effects to suppress the BMI-induced tachycardia were additive. These findings suggest that the cardiovascular effects caused by blockade of GABAergic inhibition in the DMH of the rat are dependent on activation of local NMDA and non-NMDA EAA receptors.
Developmental changes in ovine cerebral artery composition and reactivity
Authors: Pearce W. J. , Hull A. D. , Long D. M. , Longo L. D.
Published: December 2017

We have examined age-related changes in segments of common carotid (Com), basilar (Bas), posterior communicating (PC), and middle cerebral (MC) arteries taken from 14 near-term fetal lambs, 62 newborn lambs 3-7 days old, and 42 adult nonpregnant sheep. Transition from fetal to newborn life was associated with a decreased water content in all arteries ranging from 0.6% (Com) to 2.3% (Bas), no change in the relative content of cellular protein, an increase in wall thickness ranging from 4% (MC) to 26% (Com), an increase in maximum contractile tension ranging from 18% (MC) to 82% (Com), an increase in stiffness, an increase in the maximum active stress ranging from 6% (Bas) to 43% (Com), a decrease in the amine-to-potassium ratio (calculated as the maximum response to 10 microM serotonin with 20 microM histamine divided by the maximum response to 122 mM K+) ranging from 8% (Bas) to 51% (Com), and a decrease in the norepinephrine-to-potassium ratio ranging from 2.1% (Bas) to 56% (Com). Thus developmental changes associated with the transition from fetal to newborn life were much more pronounced in the larger, more proximal Com than in the smaller, more distal cerebral arteries, suggesting that, at term, the cerebral arteries are more mature both functionally and structurally than the Com arteries. Similarly, the transition from newborn to adult life was associated with much greater changes in Com characteristics than with those of the cerebral arteries. These studies demonstrate that the effects of aging vary considerably along the cerebrovascular tree and that conclusions based on developmental studies of large systemic arteries cannot be freely extrapolated to the smaller arteries of the circle of Willis.
Similar pressure pulse propagation and reflection characteristics in aortas of mammals
Authors: Li J. K. , Noordergraaf A.
Published: December 2017

Similar pressure and flow waveforms recorded in mammalian aortas suggest that pulse transmission characteristics may also be similar. We examined the validity of this hypothesis, utilizing allometric equations of pertinent hemodynamic parameters and a model of the arterial system. Results show that both the reflection coefficient and the propagation constant times the aortic length are essentially invariant across the mammalian species investigated. Resolved forward and reflected propagating waves are also similar. These findings suggest that the arterial system in these mammals indeed functions in a similar manner.
Hypertrophy of stellate ganglion cells in hypertensive, but not hyperactive, rats
Authors: Peruzzi D. , Hendley E. D. , Forehand C. J.
Published: December 2017

The dendritic complexity of peripheral autonomic neurons is positively matched with the size of the target they innervate, apparently by trophic interactions with the target (D. Purves, W. D. Snider, and J. T. Voyvodic. Nature Lond. 336: 123-128, 1988). We have asked whether the vascular hypertrophy associated with hypertension is accompanied by dendritic hypertrophy of sympathetic ganglion cells. To do this, we examined the morphology of stellate ganglion cells in the spontaneously hypertensive rat (SHR), its normotensive control Wistar-Kyoto rat (WKY), and two new strains derived from the SHR that independently express the hypertensive phenotype of the SHR (WKHT) and the behavioral hyperactivity present in the SHR (WKHA). Cells were examined by intracellular staining with horseradish peroxidase in in vitro preparations of the ganglia. Carotid arterial wall size was also examined. Significant hypertrophy of both the carotid arterial wall and stellate ganglion cell dendrites was observed in the two hypertensive strains (SHR and WKHT) but not in either of the normotensive strains (WKY and WKHA). This increased total dendritic length of stellate ganglion cells associated with hypertension provides a greater target area for preganglionic innervation that may result in hyperinnervation of these cells.
Differential temperature dependence of taste nerve responses to various taste stimuli in dogs and rats
Authors: Nakamura M. , Kurihara K.
Published: December 2017

The temperature dependence of the canine and rat chorda tympani nerve responses to various taste stimuli was examined. The temperature dependence greatly varied with species of stimuli. In the dog, the tonic responses to fructose, sucrose, acetic acid, and guanosine 5'-monophosphate (GMP) and the response induced by the synergism between monosodium glutamate (MSG) and GMP showed peaks at approximately 30 degrees C, whereas those to NaCl, NH4Cl, and MSG showed peaks between 10 and 20 degrees C. In the rat, the tonic response to NH4Cl increased with an increase in temperature up to 45 degrees C, whereas the responses to other stimuli examined showed peaks at approximately 30 degrees C. The responses to glycine, sucrose, and quinine showed sharp temperature dependence, and the responses to acids (HCl and acetic acid) and salts (NaCl and KCl) showed relatively flat dependence. The effects of the temperature change on dose-response curves for fructose, NH4Cl, and GMP were examined using dogs. The temperature change did not practically affect the thresholds for these stimuli and affected the magnitude of the responses to higher concentrations of stimuli. The origins of the temperature dependence were discussed in terms of taste receptor mechanisms.
Heart rate variability as a measure of autonomic function during weight change in humans
Authors: Hirsch J. , Leibel R. L. , Mackintosh R. , Aguirre A.
Published: December 2017

Changes in autonomic function were studied during experimentally induced weight changes in seven subjects. A spectral analysis of heart rate variability (HRV) was used to evaluate autonomic activity during weight change. With a 10% increase in body weight above the usual or starting weight, there was a decline in parasympathetic power accompanied by a rise in mean heart rate. Heart rate declined during weight reduction, but the power of HRV did not change significantly. Because heart rate power at the frequency of respiratory rate can be affected by respiratory rate, three additional subjects were tested at a constant respiratory rate. Weight increases in this group also led to a decline in the power of HRV at a frequency attributable to the parasympathetic nervous system. Such a parasympathetic effect of weight increase may be one mechanism for the arrhythmias and other cardiac alterations that accompany obesity.
Hemodynamics and organ blood flow in fetal sheep subjected to chronic anemia
Authors: Davis L. E. , Hohimer A. R.
Published: December 2017

To investigate cardiovascular adaptation to chronic anemia we studied eight ovine fetuses made anemic by serial isovolemic hemorrhage and seven nonanemic controls. After 1 wk carotid arterial oxygen content was reduced to 1.6 +/- 0.2 ml/dl and hematocrit to 13.3 +/- 1.6% in anemic fetuses compared with 6.9 +/- 1.2 ml/dl and 32.4 +/- 3.9% in controls. Cardiac output was higher in the anemic group (753 +/- 102 vs. 490 +/- 66 ml.min-1.kg fetus-1) as stroke volume and heart rate both increased. Blood flow to the carcass, skin, kidneys, intestines, brain, and heart was increased. Vascular resistance fell in all tissues except the placenta. Central venous pressure, arterial pH, plasma total protein, and blood volume were not different although extravascular fluid accumulated in six of the anemic fetuses. The estimated capillary hydrostatic pressure was greater in anemic (7.6 +/- 1.8 mmHg) than control fetuses (5.0 +/- 1.5 mmHg) and the ratio of precapillary to postcapillary resistance was less. We conclude that reduction in the ratio of precapillary to postcapillary resistance in chronic fetal anemia increases blood flow, oxygen delivery, and capillary hydrostatic pressure.
Circadian variation in human cerebrospinal fluid production measured by magnetic resonance imaging
Authors: Nilsson C. , Stahlberg F. , Thomsen C. , Henriksen O. , Herning M. , Owman C.
Published: December 2017

Recent advances in magnetic resonance imaging have made it possible to visualize and quantify flow of cerebrospinal fluid (CSF) in the brain. The net flow of CSF through the cerebral aqueduct was used to measure CSF production in six normal volunteers at different times during a 24-h period. CSF production varied greatly both intra- and interindividually. The average CSF production in each time interval showed a clear tendency to circadian variation, with a minimum production 30% of maximum values (12 +/- 7 ml/h) approximately 1800 h and a nightly peak production approximately 0200 h of 42 +/- 2 ml/h. The total CSF production during the whole 24-h period, calculated as an average of all measurements, was 650 ml for the whole group and 630 ml for repeated measurements in each time interval in one of the volunteers.
Changes in skeletal muscle gene expression consequent to altered weight bearing
Authors: Booth F. W. , Kirby C. R.
Published: December 2017

Skeletal muscle is a dynamic organ that adapts to alterations in weight bearing. This brief review examines changes in muscle gene expression resulting from the removal of weight bearing by hindlimb suspension and from increased weight bearing due to eccentric exercise. Acute (less than or equal to 2 days) non-weight bearing of adult rat soleus muscle alters only the translational control of muscle gene expression, while chronic (greater than or equal to 7 days) removal of weight bearing appears to influence pretranslational, translational, and posttranslational mechanisms of control. Acute and chronic eccentric exercise are associated with alterations of translational and posttranslational control, while chronic eccentric training also alters the pretranslational control of muscle gene expression. Thus alterations in weight bearing influence multiple sites of gene regulation.
Mechanical forces and their second messengers in stimulating cell growth in vitro
Authors: Vandenburgh H. H.
Published: December 2017

Mechanical forces play an important role in modulating the growth of a number of different tissues including skeletal muscle, smooth muscle, cardiac muscle, bone, endothelium, epithelium, and lung. As interest increases in the molecular mechanisms by which mechanical forces are transduced into growth alterations, model systems are being developed to study these processes in tissue culture. This paper reviews the current methods available for mechanically stimulating tissue cultured cells. It then outlines some of the putative “mechanogenic” second messengers involved in altering cell growth. Not surprisingly, many mechanogenic second messengers are the same as those involved in growth factor-induced cell growth. It is hypothesized that from an evolutionary standpoint, some second messenger systems may have initially evolved for unicellular organisms to respond to physical forces such as gravity and mechanical perturbation in their environment. As multicellular organisms came into existence, they appropriated these mechanogenic second messenger cascades for cellular regulation by growth factors.
Fetal iron and cytochrome c status after intrauterine hypoxemia and erythropoietin administration
Authors: Georgieff M. K. , Schmidt R. L. , Mills M. M. , Radmer W. J. , Widness J. A.
Published: December 2017

Chronic fetal hypoxemia stimulates erythropoiesis and may result in a redistribution of fetal iron from plasma into erythrocytes. We studied the response of fetal plasma erythropoietin (Ep) to hypoxemia, the role of Ep in stimulating erythropoiesis in utero, and the effect of augmented erythropoiesis on fetal plasma Ep and iron and tissue cytochrome c concentrations in 19 chronically instrumented late-gestation fetal sheep. The fetuses were stimulated to produce 28 erythropoietic responses after exposure to 1) acute hypoxemia (1-5 days), 2) chronic hypoxemia (greater than 7 days), and/or 3) administration of 1,500 U recombinant human Ep concurrently during normoxemia. Plasma Ep peaked less than 12 h after the onset of hypoxemia or Ep bolus. Plasma iron decreased 24-48 h later and returned to baseline 48-96 h after normalization of Ep levels to baseline. The plasma iron response was directly related to the erythropoietin stimulus (r = 0.79, P less than 0.001) and inversely related to liver iron concentration at death (r = -0.84, P less than 0.001). Nine fetuses with depleted liver iron concentrations at autopsy had significantly lower heart and skeletal muscle iron concentrations compared with animals with 10% of control liver iron remaining. Skeletal muscle and heart iron and cytochrome c concentrations were significantly correlated. Ep has a potent biological effect on fetal erythropoiesis and iron metabolism. Augmented fetal erythropoiesis, mediated by Ep, results in decreased plasma iron, hepatic storage iron, and skeletal and cardiac muscle iron and cytochrome c. The model potentially explains the iron abnormalities found in newborn infants after fetal hypoxia.
Spatial and temporal differing control of sympathetic activities during hemorrhage
Authors: Koyama S. , Sawano F. , Matsuda Y. , Saeki Y. , Shibamoto T. , Hayashi T. , Matsubayashi Y. , Kawamoto M.
Published: December 2017

We performed simultaneous multifiber recordings of cardiac, renal (RNA), hepatic (HNA), adrenal, and splenic sympathetic nerve activities during 10 min of sustained hemorrhagic hypotension to a mean blood pressure of 50 mmHg. One minute after bleeding in dogs with intact baroreceptors, all measured nerve activities increased significantly, and a gradual decline toward prebleeding level followed. Only RNA showed a great inhibition below prebleeding level. In cervically vagotomized dogs, all nerve activities showed significantly higher levels than prebleeding control throughout the experiment. The initial increase in HNA observed at 1 min postbleeding in animals with intact baroreceptors was attenuated. HNA in the vagotomized group showed a gradual increase so that 5 min postbleeding, HNA reached a peak level that was maintained until the end of the experiment. Sympathoinhibition in RNA and decrease in heart rate during hemorrhagic hypotension were reversed to significant increases after vagotomy. In contrast, animals with denervation of the carotid sinus and aortic nerves showed initial increases in nerve activities followed by recovery to prebleeding control level within 2 min postbleeding. After complete denervation of systemic baroreceptors, rapid hemorrhage did not cause any significant change in sympathetic nerve activity in any nerve. These results indicate that early reflex response to hemorrhage in regional sympathetic nerves is unidirectional sympathoexcitation mediated by summative unloading of both arterial baroreceptors and cardiopulmonary receptors. When greater than 1 min passed after bleeding and sustained hypotension of 50 mmHg was established, a reflex mechanism through the vagal afferents participated to inhibit the unidirectional sympathoexcitation mediated by unloading of arterial baroreceptors, with different magnitude in different innervated organs.(ABSTRACT TRUNCATED AT 250 WORDS)
C-type natriuretic peptides stimulate chloride secretion in the rectal gland of Squalus acanthias
Authors: Solomon R. , Protter A. , McEnroe G. , Porter J. G. , Silva P.
Published: December 2017

Homologous shark C-type natriuretic peptide (sCNP) was infused as a bolus and as a constant infusion in the isolated perfused rectal gland of the same species, Squalus acanthias. sCNP was a potent stimulator of chloride secretion similar in its dose-response curve to vasoactive intestinal peptide. sCNP was equipotent with killifish CNP but more potent than human CNP (hCNP). Truncated and substituted, forms of hCNP were also capable of stimulation of chloride secretion in the order hCNP greater than hCNP (6-22) = [Gly9]hCNP greater than hCNP-(7-21). sCNP was more potent than human atrial natriuretic peptide (hANP), which was more potent than porcine brain natriuretic peptide. hANP-(31-67) was without effect. These studies suggest that sCNP may be the physiological regulator of rectal gland function. The receptor in the rectal gland is unknown but based on the order of potencies, position 4 in the NH2-terminal end and the ring itself are important for ligand effects.
Mechanism of intracardiac shunting in the turtle Pseudemys scripta
Authors: Hicks J. W. , Malvin G. M.
Published: December 2017

Two principal hypotheses account for right-left (R-L) intracardiac shunting in reptiles. The “pressure shunting” hypothesis proposes no functional separation between the ventricular cava during systole. The “washout shunting” hypothesis suggests that during systole, the cavum pulmonale (CP) is functionally separate from the rest of the ventricle. The purpose of this study was to test these hypotheses during control, after acetylcholine (ACh) administration, after epinephrine (Epi) administration, and during apnea. Anesthetized (pentobarbital) turtles (Pseudemys scripta) were mechanically ventilated and three nonocclusive catheters were implanted into the right atrium (RAt), left atrium (LAt), and CP. In addition, three blood gas catheters connected to a mass spectrometer were implanted into the RAt, LAt, and right or left aortic arch for measurement of PO2. A tracer gas, He dissolved in saline, was sequentially injected into the three cardiac chambers and was detected by the mass spectrometer. The presence of R-L shunting was assessed with the blood PO2 and PHe measurements. ACh produced R-L shunting in all animals. No R-L shunting occurred after Epi administration and 20 min of apnea. In all animals after ACh administration, He was detected in an aorta after He infusion in the RAt and LAt, but never after infusion of He into the CP. These results from this preparation are inconsistent with the pressure hypothesis and support the washout hypothesis of intracardiac shunting.
Cryomicroscopic analysis of freezing in liver of the freeze-tolerant wood frog
Authors: Storey K. B. , Bischof J. , Rubinsky B.
Published: December 2017

The technique of directional solidification coupled with low-temperature scanning electron microscopy was applied to analyze the freezing of liver slices from the freeze-tolerant frog Rana sylvatica. Micrographs of liver slices from 5 degrees C-acclimated frogs frozen on the directional stage to -7 degrees C showed continuous ice formed along an expanded vasculature with hepatocytes that were shrunken and virtually dehydrated. However, when frogs were given a survivable freezing exposure at -4 degrees C for 24 h, liver slices subsequently frozen in vitro at -7 degrees C were much less shrunken and the presence of intracellular ice crystals (formed when samples were plunged into liquid N2 before microscopy) demonstrated that ample free water remained in these hepatocytes at -7 degrees C. This reduced level of cell dehydration was correlated with the buildup of 280 +/- 61 mumol/g wet wt glucose as a cryoprotectant in liver during the -4 degrees C exposure in vivo. The study provides the first direct cytological analysis of the freezing process in an organ of a freeze-tolerant vertebrate and the first confirmation of the relationship between maintenance of a critical minimum cell volume and freezing survival by these animals.
Effects of hydration state on exercise thermoregulation in goats
Authors: Nijland M. J. , Baker M. A.
Published: December 2017

In this study we asked how exercise affects sweating and panting and how dehydration affects exercise thermoregulation in goats. Six goats exercised (4.8 km/h, +10% slope) for 45 min at an ambient temperature of 35 degrees C when hydrated and after 48 h without drinking water. Hematocrit (Hct), plasma protein concentration (PP), and plasma osmolality were elevated by dehydration (P less than or equal to 0.05). Hct and plasma osmolality increased further during exercise in hydrated and dehydrated animals (P less than or equal to 0.05), but PP rose only in hydrated goats (P less than or equal to 0.05). The increase in central blood temperature (Tbl) during exercise was greater in dehydrated than in hydrated animals (P less than or equal to 0.001). Evaporation by panting (Eresp) and sweating were linearly related to Tbl during exercise. The relationship between Eresp and Tbl was not affected by dehydration, but dehydrated animals showed an increased Tbl threshold for sweating. We postulate that the elevation in threshold for sweating may be due primarily to increased body fluid osmolality, and that hypovolemia may not play a significant role in the thermoregulatory adjustments to exercise in dehydrated goats.
Calcium channel blockers inhibit amiloride-stimulated short-circuit current in frog tadpole skin
Authors: Cox T. C.
Published: December 2017

The larval frog skin has a very high electrical resistance and a corresponding low rate of transepithelial ion transport. Amiloride, a blocker of sodium transport in adult skin, transiently stimulates rather than inhibits short-circuit current (Isc) across larval skin. The time course and concentration response to amiloride and the effects of calcium channel blockers on Isc were studied with larval frog skin mounted in modified Ussing chambers. The amiloride (1 mM) transient was markedly blunted if the skin was previously exposed to low amiloride (0.01-0.1 mM) concentrations. The calcium channel blockers verapamil, nitrendipine, diltiazem, W-7, and lanthanum all blocked the amiloride transient. Diltiazem itself caused a rapid transient in Isc, indicating that it may be a partial agonist. These data suggest that the amiloride-stimulated cation channels rapidly desensitize in a manner similar to the acetylcholine receptor. The decline in Isc after amiloride stimulation could be caused by amiloride block of the open channel. Blockade of amiloride stimulation by well-known calcium channel blockers suggests that these larval cation channels may have some characteristics in common with calcium channels.
Effect of age and blood pressure on the heart rate, vasopressin, and renin response to hypoxia in fetal sheep
Authors: Raff H. , Wood C. E.
Published: December 2017

The purpose of these studies was to determine whether attenuating the increase in arterial and central venous pressure (CVP) during acute hypoxia can augment the renin and arginine vasopressin (AVP) responses to isocapnic hypoxia in chronically instrumented sheep fetuses. Young (122 +/- 2 days; n = 7) and old (133 +/- 1 days, n = 7) fetuses were exposed to hypoxemia (arterial PO2 = approximately 12-13 Torr) without and with attenuation of the increase in mean arterial pressure (MAP) and CVP with the simultaneous infusion of sodium nitroprusside (NP). NP did not attenuate the bradycardia induced by hypoxia. Plasma renin activity did not increase with hypoxia even when the potentially inhibitory effect of increased MAP and CVP was attenuated with NP. The AVP response to hypoxia was greater in the old fetuses. Furthermore, NP did augment the AVP response to hypoxia in the young but not old fetuses. We conclude that increases in MAP and CVP (i.e., baroreceptor input) do not influence the decrease in heart rate and lack of renin responses to acute hypoxia in the sheep fetus and that increased MAP and CVP seems to restrain the AVP response to hypoxia in younger sheep fetuses.
Renal medullary interstitial infusion of diltiazem alters sodium and water excretion in rats
Authors: Lu S. , Roman R. J. , Mattson D. L. , Cowley A. W.
Published: December 2017

The role of renal papillary blood flow in regulation of fluid and electrolyte excretion was examined. The effects of an acute infusion of diltiazem (5 micrograms.kg-1 x min-1) into the renal medullary interstitium on papillary blood flow and sodium and water excretion were studied. Changes of renal blood flow were measured using an electromagnetic flow probe. Cortical and papillary blood flows were measured using laser-Doppler flowmetry. Renal and cortical blood flows were unchanged during medullary interstitial infusion of diltiazem, but papillary blood flow increased 26% (P < 0.05) and remained elevated for 1 h after diltiazem infusion was discontinued. Glomerular filtration rate (GFR) of the infused kidney increased by 21% from a control of 1.0 +/- 0.1 ml.min-1 x g-1 during infusion of diltiazem (P < 0.05), but it returned to control after diltiazem infusion was stopped. Urine flow and sodium excretion increased by 70% (P < 0.05), and fractional sodium excretion rose from 1.5 +/- 0.2 to 2.4 +/- 0.3% of the filtered load during the hour after diltiazem infusion. Renal blood flow, cortical and papillary blood flow, GFR, urine flow, and sodium excretion in the 0.9% sodium chloride vehicle-infused kidney were not significantly altered during the experiment. Intravenous infusion of the same dose of diltiazem (5 micrograms.kg-1 x min-1) increased GFR by 22%, but had no effect on urine flow and sodium excretion. These results indicate that renal medullary interstitial infusion of diltiazem selectively increased renal papillary blood flow, which was associated with an increase of sodium and water excretion.
Role of sympathetic innervation in brown adipocyte proliferation
Authors: Geloen A. , Collet A. J. , Bukowiecki L. J.
Published: December 2017

The role of sympathetic nerves in the control of brown adipose tissue (BAT) growth was studied by quantitative photonic autoradiography using [3H]-thymidine to follow mitotic activity. The effects of cold exposure (4 days at 5 degrees C) and chronic norepinephrine treatment (0.375 mumol/h for 4 days at 25 degrees C) were compared in intact and denervated interscapular BAT pads of adult rats. The denervated pads were paler than the contralateral innervated sides and contained numerous adipocytes filled with large lipid droplets. In the innervated BAT pad, cold exposure markedly enhanced the labeling frequency in brown adipocyte precursor cells (interstitial cells and preadipocytes) and in endothelial cells forming the numerous blood capillaries (P < 0.01). However, in the denervated BAT pads, the effects of cold exposure on cell proliferation were markedly inhibited. Remarkably, norepinephrine infusion at 25 degrees C mimicked the effects of cold exposure on the coordinated proliferation of the different cellular types, both in the innervated and denervated pads. These results demonstrate that intact sympathetic nerves are required for the stimulation of mitotic activity in BAT by cold exposure but not by norepinephrine infusion. It appears therefore that norepinephrine release from sympathetic nerves represents the initial stimulus in a chain of metabolic events leading to BAT hyperplasia. However, sympathetic or sensory nerves may still contain factors modulating cell proliferation and differentiation in BAT.
Medullary pathway of the Bezold-Jarisch reflex in the rat
Authors: Verberne A. J. , Guyenet P. G.
Published: December 2017

The central pathway mediating the Bezold-Jarisch reflex elicited by jugular vein injection of serotonin (5-HT) and phenyl biguanide (PBG) was studied in halothane-anesthetized, paralyzed rats. 5-HT and PBG produced hypotension and inhibition of lumbar sympathetic discharge often preceded by sympathoexcitation. The Bezold-Jarish reflex was blocked by bilateral kynurenic acid (KYN; glutamate antagonist, 1.25 nmol/side) microinjection into the solitary tract nucleus. Bilateral KYN injection into the caudal ventrolateral medulla (5 nmol/side) also blocked the reflex. Bilateral injection of bicuculline methiodide (BIC; 100 pmol/side) into the rostral ventrolateral medulla (RVL) reduced the depressor and sympathoinhibitory components of the reflex and enhanced an excitatory component. Blockade or attenuation of the Bezold-Jarisch reflex was always associated with a concomitant blockade or attenuation of the arterial baroreflex. RVL barosensitive neurons (n = 61) were inhibited (> 60% reduction in firing) by PBG and 5-HT. Iontophoretic application of BIC (n = 11 cells), but not strychnine (glycine antagonist), blocked inhibition of RVL neurons by 5-HT and PBG. The sympathoinhibitory component of the Bezold-Jarisch reflex may use a central pathway similar to that of the arterial baroreflex.
Secretagogue-induced 86Rb+ efflux from bovine parotid is HCO3- dependent
Authors: Lee S. I. , Turner R. J.
Published: December 2017

Muscarinic agonist (carbachol)-induced K+ loss from a bovine parotid mince was studied using 86Rb+ as a K+ marker. In contrast to our previous studies with the rat parotid [Am. J. Physiol. 261 (Gastrointest. Liver Physiol. 24): G111-G118, 1991] in which both Cl(-)-dependent and HCO3(-)-dependent components of carbachol-induced 86Rb+ efflux were observed, no significant evidence for Cl(-)-dependent 86Rb+ loss was detected in the bovine parotid. HCO3(-)-dependent agonist-induced 86Rb+ loss was blunted by K+ and Cl- channel blockers and by removal of extracellular Ca2+, consistent with the hypothesis that this 86Rb+ loss occurs via a Ca(2+)-activated K+ channel and that this cation loss serves to electrically balance the concomitant loss of HCO3- via an electrically conductive pathway, presumably an apical anion channel. Acetate, formate, and propionate could substitute for HCO3-. Interpreted in terms of current models of salivary fluid secretion, which hypothesize that the production of fluid is secondary to anion secretion accompanied by an electrically coupled K+ loss, these results indicate that salivary production in the bovine parotid is driven almost exclusively by acinar HCO3- secretion.
Effect of fibronectin on permeability of normal and TNF-treated lung endothelial cell monolayers
Authors: Wheatley E. M. , Vincent P. A. , McKeown-Longo P. J. , Saba T. M.
Published: December 2017

Fibronectin is found in a soluble form in plasma and lymph and in an insoluble form in the extracellular matrix. Plasma fibronectin can incorporate into the tissue pool of fibronectin where its adhesive properties may influence cell-cell interaction, cell adhesion to a collagenous matrix, and vascular integrity. Elevation of plasma fibronectin can attenuate the increase in lung vascular permeability in sheep during postoperative gram-negative bacteremia, and plasma fibronectin deficiency can magnify the increase in lung vascular permeability with postoperative sepsis. Using pulmonary endothelial monolayers, we determined if exogenous human plasma fibronectin (pFn) would influence the protein permeability of pulmonary endothelial monolayers as determined by transendothelial clearance (microliters/min) of 125I-albumin after they were exposed to human recombinant tumor necrosis factor-alpha. Treatment of endothelial monolayers with tumor necrosis factor (TNF) (200 U/ml) for 18 h resulted in a significant (P < 0.05) increase in protein permeability. Addition of intact purified human plasma fibronectin to normal confluent endothelial monolayers to yield a medium concentration of 300, 600, and 900 micrograms/ml for 18 h had no effect on baseline protein permeability. In contrast, whereas addition of lower amounts of human plasma fibronectin (300 micrograms/ml) did not attenuate the TNF-induced increase in monolayer permeability, the higher concentrations of 600 or 900 micrograms pFn/ml significantly decreased (P < 0.05) protein permeability. The ability of soluble plasma fibronectin to attenuate the TNF-induced increase in endothelial protein permeability required an incubation time of at least 2-3 h, perhaps due to a lag time required for its incorporation into the extracellular matrix.(ABSTRACT TRUNCATED AT 250 WORDS)
C-type natriuretic peptide: a selective cardiovascular peptide
Authors: Clavell A. L. , Stingo A. J. , Wei C. M. , Heublein D. M. , Burnett J. C.
Published: December 2017

Studies were performed in three groups of anesthetized dogs to compare the structurally related peptides atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). Group 1 (n = 5) and group 2 (n = 4) received intravenous infusions of CNP or ANP respectively at doses of 10 ng.kg-1.min-1 and 100 ng.kg-1.min-1. Group 3 (n = 5) received CNP intrarenally at doses of 1 ng.kg-1.min-1 and 5 ng.kg-1.min-1. Intravenous infusion of CNP resulted in a greater decrease in blood pressure when compared with ANP. This marked decrease in blood pressure observed with CNP was associated with a significantly smaller increase in guanosine 3',5'-cyclic monophosphate (cGMP). In contrast, neither intravenous nor intrarenal administration of CNP was associated with natriuresis as observed with ANP. The current study also demonstrates the presence of CNP immunoreactivity in canine plasma at low picomolar concentrations. Further characterization by gel permeation chromatography demonstrated that circulating CNP immunoreactivity corresponds to the 22-amino acid form of the peptide. In conclusion, this study demonstrates that CNP circulates in low picomolar concentrations and is potently vasoactive in vivo, suggesting a potential role in the regulation of vascular tone.
Chorda tympani section decreases the cation specificity of depletion-induced sodium appetite in rats
Authors: Breslin P. A. , Spector A. C. , Grill H. J.
Published: December 2017

Rats depleted of sodium by diuretic treatment were tested for their ability to respond selectively to NaCl after chorda tympani nerve (CTn) section (CTX). A variety of chloride salts (NaCl, KCl, NH4Cl, CaCl2) at two concentrations (0.05 and 0.3 M) were presented semirandomly to sodium-deplete rats in repeated single-stimulus trials (10 s). The responses of sodium-depleted surgical control rats (n = 8) were highly cation specific. These rats licked substantially more for both sodium stimuli than for any other chloride salt. On the other hand, the licking responses of CTX sodium-depleted rats (n = 8) were less cation selective. These rats licked NaCl and 0.05 M KCl at comparable rates. For both NaCl concentrations, CTX rats had significantly lower lick rates than controls. In addition, the difference between the lick rate for NaCl and that for the other salts was much greater for control rats than for CTX rats. Although CTn section did not entirely eliminate the high levels of responsivity to NaCl observed in the intact sodium-depleted rat, it did substantially compromise the selectivity of the behavior, which suggests that the input of the CTn is critical for taste-guided sodium specific behaviors.
Cardiovascular change and hypothalamic norepinephrine release in response to environmental stress
Authors: Nakata T. , Berard W. , Kogosov E. , Alexander N.
Published: December 2017

The major objective of this study was to compare the magnitude and duration of cardiovascular (CV) responses to acute environmental stresses with the associated patterns of noradrenergic activity in the paraventricular nucleus (PVN) and posterior nucleus (PH) of the hypothalamus. Simultaneous microdialysis samples of extracellular norepinephrine (NE) were collected at 5-min intervals from PVN and PH and the CV responses were recorded before, during, and for 15 min after acute shaker (cage oscillation) stress or inhalation of ether vapor in freely moving rats. Five minutes of shaker stress, 60 and 150 cycles/min, elicited pressor responses coupled with increases in dialysate NE from both PVN and PH in a frequency-dependent manner. Tachycardia occurred at 150 but not 60 cycles/min. Ten minutes after 60 cycles/min and 15 min after 150 cycles/min, NE efflux in PH was still increased, whereas in PVN it returned to control as had arterial pressure and heart rate. Ether vapor elicited a transient CV response but a continuing efflux of NE in PH and PVN. Urethan anesthesia raised baseline values of dialysate NE in PH and PVN but significantly attenuated cardiovascular and dialysate NE responses to shaker stress. We conclude that acute environmental stress simultaneously elicits CV responses and the efflux of NE from PVN and PH but, during or after stress, CV values may return to control levels while NE efflux remains elevated in PVN and/or PH.
Membrane properties of organum vasculosum lamina terminalis neurons recorded in vitro
Authors: Nissen R. , Bourque C. W. , Renaud L. P.
Published: December 2017

Intracellular recordings of organum vasculosum lamina terminalis (OVLT) neurons were obtained from superfused explants of rat hypothalamus. Most (32 of 34) OVLT neurons displayed a low threshold spike response during depolarizing pulses applied from holding membrane potentials negative to -70 mV. In 17 of 34 cells, electrical stimulation of the supraoptic nucleus area evoked antidromic responses. In 20 of the 34 cells, 8 of which were antidromically driven, identical stimuli also revealed either excitatory (n = 12) or inhibitory (n = 5) or mixed (n = 3) postsynaptic potentials. Axonal projections to the ipsilateral supraoptic nucleus were confirmed afterwards using reconstruction of Lucifer yellow-filled cells. A 10-40 mosmol/kgH2O increase in the osmolality of the superfusion media by addition of NaCl or mannitol prompted a membrane depolarization of 2-10 mV in each of nine OVLT neurons tested. These results indicate that OVLT neurons project to the supraoptic nucleus and possess intrinsic properties capable of influencing their excitability. Because neurons in OVLT depolarize consequent to elevations in media osmolality, the OVLT may provide a means by which hyperosmotic stimuli influence neuroendocrine function.
Response of tissues of the rat to anisosmolality in vivo
Authors: Bedford J. J. , Leader J. P.
Published: December 2017

Rats were exposed to osmotic stress either acutely, over periods of 1 or 4 h, or chronically, over several days. In acute experiments, hyposmolality was induced by intraperitoneal infusion of dilute glucose or mannitol solutions, whereas hyperosmolality was induced by use of sodium chloride, concentrated glucose or mannitol solutions, or urea. Chronic hypernatremia was induced by daily administration of sodium chloride to water-deprived animals; chronic hyponatremia was induced by daily injection of antidiuretic hormone supplemented with glucose. Animals were made hyperglycemic using streptozotocin or uremic by ureteral ligation. Where appropriate, animals were anesthetized with thiobutabarbital (Inaktin) or ether. In acute experiments, analysis of the composition of the cardiac ventricle, diaphragm, liver, and renal cortex showed no evidence of cell volume regulatory processes involving transmembrane movement of potassium ions. There was a small but significant increase in free amino acids [measured as ninhydrin-positive substance (NPS)] in cardiac muscle exposed to hypertonic solutions of sodium chloride and glucose but not when plasma osmolality was raised using mannitol. In cerebral cortical tissue, after 4 h of exposure to acute hypertonicity by infusion of sodium chloride or glucose, there was a significant increase in tissue potassium content and a slight increase in NPS content. In chronic experiments, tissue analysis revealed good evidence for cellular volume readjustment only in cerebral cortex and heart. In the cortex, levels of free amino acids, principally taurine and glutamate (plus glutamine), showed large increases during hypernatremia and hyperglycemia and corresponding decreases during hyposmolality. In heart the principal amino acid present was taurine, and it, together with aspartate and glutamate (plus glutamine), showed large changes under osmotic stress. Other tissues analyzed showed only small changes in composition.
Autonomic control of pancreatic polypeptide and glucagon secretion during neuroglucopenia and hypoglycemia in mice
Authors: Havel P. J. , Akpan J. O. , Curry D. L. , Stern J. S. , Gingerich R. L. , Ahren B.
Published: December 2017

Neural control of pancreatic polypeptide (PP) release has not been previously investigated in the mouse. In addition, it is not known to what extent increased glucagon secretion during hypoglycemia in mice is neurally mediated vs. an effect of hypoglycemia to directly stimulate glucagon secretion at the level of the islet. Feeding or the cholinergic agonist carbachol increased plasma PP levels in conscious mice (+74 +/- 18 pg/ml vs. fasted mice and +141 +/- 17 pg/ml vs. control, respectively). Neuroglucopenia induced by 2-deoxy-D-glucose or insulin-induced hypoglycemia also increased plasma PP (+79 +/- 18 and +89 +/- 11 pg/ml vs. control, respectively). These increases were abolished by hexamethonium and reduced by atropine methylnitrate (atropine). Hypoglycemia-induced hyperglucagonemia (+1,243 +/- 275 pg/ml) was reduced to 31 +/- 7% of control by atropine (+382 +/- 85 pg/ml), to 48 +/- 9% of control by combined adrenergic blockade (+601 +/- 112 pg/ml), and nearly abolished by atropine plus combined blockade (+143 +/- 41 pg/ml; 11 +/- 3% of control) or hexamethonium (+151 +/- 38 pg/ml; 12 +/- 3% of control). We conclude the following in the mouse. 1) Feeding or cholinergic agonists increase plasma PP. 2) During neuroglucopenia or hypoglycemia, plasma PP is increased via nicotinic and muscarinic mechanisms. 3) The glucagon response to hypoglycemia is predominantly the result of autonomic activation and is mediated by both muscarinic and adrenergic mechanisms.
Induction of c-fos expression in spinal neurons by nociceptive and nonnociceptive stimulation of LUT
Authors: Birder L. A. , de Groat W. C.
Published: December 2017

Expression of c-fos gene in spinal neurons was detected with an immunocytochemical technique to study the spinal processing of nociceptive and nonnociceptive input from the lower urinary tract (LUT) of the urethan-anesthetized rat. Two preparations were used to activate afferent pathways in the LUT: 1) the urinary bladder was exposed through an abdominal incision, and saline or 1% acetic acid solution was infused directly into the bladder lumen and expelled through the urethra; and 2) the bladder was catheterized through the urethra, and the urethral outlet was ligated to allow distension and reflex contractions to occur under isovolumetric conditions. The first preparation mimicked the physiological changes occurring during normal voiding, whereas the second preparation generated high (presumably nociceptive) pressures when the bladder contracted against a closed outlet. The results indicate that distension-induced voiding increased c-fos expression largely in the region of the sacral parasympathetic nucleus (52% of the total number of cells/L6 section) and the dorsal commissure (25% of the total number of cells), whereas nociceptive stimuli markedly increased the number of c-fos-positive cells in the dorsal commissure (3.5 x increase above the number induced by distension, representing 50% of the total number of cells/L6 section). Bladder contractions against a closed outlet elicited a distribution of c-fos-positive cells similar to that induced by chemical irritation. Drugs that suppressed bladder reflexes did not reduce c-fos induced by distension, indicating that voiding reflexes do not contribute to c-fos expression.
Cholecystokinin octapeptide analogues suppress food intake via central CCK-A receptors in mice
Authors: Hirosue Y. , Inui A. , Teranishi A. , Miura M. , Nakajima M. , Okita M. , Nakajima Y. , Himori N. , Baba S. , Kasuga M.
Published: December 2017

To examine the mechanism of the satiety-producing effect of cholecystokinin (CCK) in the central nervous system, we compared the potency of intraperitoneally (ip) or intracerebroventricularly (icv) administered CCK-8 and its analogues on food intake in fasted mice. The icv administration of a small dose of CCK-8 (0.03 nmol/brain) or of Suc-(Thr28, Leu29, MePhe33)-CCK-7 (0.001 nmol/brain) suppressed food intake for 20 min, whereas CCK-8 (1 nmol/kg, which is equivalent to 0.03 nmol/brain) or Suc-(Thr28, Leu29, MePhe33)-CCK-7 (1 nmol/kg) had satiety effect after ip administration. Dose-response studies indicated the following rank order of potency: Suc-CCK-7 > or = Suc-(Thr28, Leu29, MePhe33)-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of ip administration and Suc-(Thr28, Leu29, MePhe33)-CCK-7 >> Suc-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of icv administration. The selective CCK-A receptor antagonist MK-329 reversed the inhibitory effect of the centrally as well as peripherally administered CCK-8, or of Suc-(Thr28, Leu29, MePhe33)-CCK-7, whereas the selective CCK-B receptor antagonist L-365260 did not. The icv administered CCK-8 did not appear in the peripheral circulation. These findings suggest the participation of CCK-A receptors in the brain in mediating the satiety effect of CCK and the difference in CCK-A receptors in the brain and peripheral tissues.