bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypothalamic glutamatergic input to medullary sympathoexcitatory neurons in rats
Authors: Sun M. K. , Guyenet P. G.
Published: December 2017

In the halothane-anesthetized paralyzed rat, electrical or chemical stimulation of lateral hypothalamic sites dorsolateral to the fornix produced pressor effects, increases in lumbar sympathetic nerve discharge (SND), and excitation of the majority of bulbospinal sympathoexcitatory neurons of nucleus paragigantocellularis lateralis (PGCL sympathoexcitatory neurons). The relationship between SND and mean arterial pressure (MAP) was shifted upward by electrical hypothalamic stimulation, whereas the gain of the baroreflex was unchanged. A similar upward shift of the relationship between the discharge rate of PGCL sympathoexcitatory neurons and MAP was observed during stimulation. The excitatory effect of L-glutamate on PGCL sympathoexcitatory neurons was blocked by iontophoretic applications of kynurenic acid, whereas identical amounts of 8-OH kynurenic acid were ineffective. Bilateral pressure injections of kynurenic acid (but not of 8-OH kynurenic acid) into nucleus PGCL markedly reduced the pressor and sympathoexcitatory effects of hypothalamic stimulation without altering the on-going level of SND or its baroreflex inhibition. Applied by iontophoresis, kynurenic acid also attenuated the excitation of PGCL sympathoexcitatory neurons produced by hypothalamic stimulation. It is concluded that descending sympathoexcitatory pathways, originating in part in the lateral hypothalamus, relay in nucleus PGCL. This relay involves synapses that release an endogenous glutamate receptor agonist. These results suggest that synaptic integration between these glutamatergic inputs and gamma-aminobutyric acid baroreceptor inputs occurs in the immediate vicinity of PGCL bulbospinal sympathoexcitatory neurons or perhaps directly on their somadendritic surface.
Total peripheral resistance during cardiac tamponade: adrenergic and angiotensin roles
Authors: Cogswell T. L. , Bernath G. A. , Raff H. , Hoffmann R. G. , Klopfenstein H. S.
Published: December 2017

During progressive cardiac tamponade in conscious dogs, cardiac output falls continuously while arterial blood pressure is maintained until cardiovascular decompensation by increases in total peripheral resistance (TPR). Plasma renin activity (PRA) is known to increase at decompensation. We hypothesized that the increase in TPR during cardiac tamponade was mediated by alpha-adrenergic and renin-angiotensin mechanisms. Twelve adult dogs were instrumented to measure cardiac output (electromagnetic flow probe), aortic and right atrial blood pressures, and intrapericardial pressure (IPP). TPR was calculated as the conscious euvolemic animals underwent cardiac tamponade induced by intrapericardial saline infusion at 20 ml/min. Six dogs underwent cardiac tamponade in the control condition (no medications) and during independent alpha- and beta-adrenergic and angiotensin-converting enzyme (ACE) inhibition. PRA and angiotensin II (ANG II) were measured during control tamponade. We found that TPR increased continuously to levels of greater than 200% of base line as IPP rose during cardiac tamponade (P less than 0.01). This increase in TPR was unaffected by beta-adrenergic or ACE blockade but was blunted by alpha-adrenergic blockade. PRA and ANG II increased only at decompensated tamponade (P less than 0.05) when arterial blood pressure had fallen by 30%. These changes in PRA and ANG II during tamponade were not altered by beta-blockade in six separate animals. We conclude that cardiac tamponade stimulates renin release and ANG II generation by a non-beta-receptor-mediated mechanism. The increase in TPR during cardiac tamponade is primarily dependent on alpha-adrenergic mechanisms, with a limited late contribution from the renin-angiotensin system.
Spaceflight effects on adult rat muscle protein, nucleic acids, and amino acids
Authors: Steffen J. M. , Musacchia X. J.
Published: December 2017

Exposure to conditions of weightlessness has been associated with decrements in muscle mass and strength. The present studies were undertaken to determine muscle responses at the cellular level. Male Sprague-Dawley rats (360–410 g) were exposed to 7 days of weightlessness during the Spacelab-3 shuttle flight (May 1985). Animals were killed 12 h postflight, and soleus (S), gastrocnemius (G), and extensor digitorum longus (EDL) muscles were excised. Muscle protein, RNA, and DNA were extracted and quantified. Differential muscle atrophy was accompanied by a significant (P less than 0.05) reduction in total protein only in S muscles. There were no significant changes in protein concentration (mg/g) in the muscles examined. In S muscles from flight animals, sarcoplasmic protein accounted for a significantly greater proportion of total protein that in ground controls (37.5 vs. 32.5%). Tissue concentrations (nmol/g) of asparagine-aspartate, glutamine-glutamate, glycine, histidine, and lysine were significantly reduced (from 17 to 63%) in S muscles from flight animals, but only glutamine-glutamate levels were decreased in the G and EDL. Muscle DNA content (microgram) was unchanged in the tissues examined, but S muscle DNA concentration (micrograms/mg) increased 27%. RNA content (micrograms) was significantly (P less than 0.025) reduced in S (-28%) and G(-22%) muscles following spaceflight. These results identify specific alterations in rat skeletal muscle during short term (7-day) exposure to weightlessness and compare favorably with observations previously obtained from ground-based suspension simulations.
Menstrual cycle and sensitivity of human fallopian tube to prostaglandins
Authors: Nozaki M. , Ito Y.
Published: December 2017

The shapes and frequencies of spontaneous contractions of circular muscle strips of the human oviduct differ during the menstrual cycles. However, under given conditions, the frequency and amplitude of the contractions were continuously reduced during perfusion with Krebs solution. In the presence of prostaglandin (PG) synthesis inhibitors or an antagonist, a gradual and continuous reduction was no longer observed, and low concentrations (10(-15)-10(-10) M) of PGE2 markedly suppressed the amplitude and frequency of the spontaneous contractions. The highest sensitivity of smooth muscle cells to PGE2 was observed during the periovulatory phases. Spontaneous prepotentials followed by slow waves were observed, and the latter potentials triggered contraction of the tissue. PGE2 (10(-14)-10(-12) M) inhibited, and PGF2 alpha (10(-9)-10(-7) M) enhanced the frequency of these slow waves. The amount of PGE series released from the tissues was twice of PGF series. These results suggest that endogenous prostaglandins play a physiological role in the transport of ovum in the human fallopian tube as a result of the regulation of spontaneous membrane and mechanical activities.
Comparison of ventromedial and paraventricular lesions in rats that become obese
Authors: Tokunaga K. , Fukushima M. , Kemnitz J. W. , Bray G. A.
Published: December 2017

Lesions in the ventromedial hypothalamus (VMH) uniformly produced obesity, but lesions in the paraventricular nucleus (PVN) produced obesity in only half of the animals. The obesity in the PVN-lesioned animals was related to the extent of PVN damage and was attenuated by concurrent damage to the dorsomedial nucleus. Comparing the PVN-lesioned rats that became obese with the VMH-lesioned rats that showed comparable weight gain, revealed several differences. The nocturnal intake of food in rats eating ad libitum was lower in the VMH-lesioned rats. Glucose concentrations were also lower in the VMH-lesioned rats, whether eating ad libitum or pair fed. Insulin concentrations were higher in the fatter animals fed ad libitum regardless of the location of the lesion. After pair feeding the insulin values were lower in both VMH- and PVN-lesioned rats than in controls. The diurnal excursion of corticosterone was blunted by both hypothalamic lesions in rats fed ad libitum, but after pair feeding there was less distortion of the diurnal rhythm. These data show that the characteristics of obesity produced by PVN lesions differ from those resulting from VMH damage.
Natriuresis induced by localized perfusion within the third cerebral ventricle of sheep
Authors: Cox P. S. , Denton D. A. , Mouw D. R. , Tarjan E.
Published: December 2017

Push-pull perfusion was performed at four different sites in the third cerebral ventricle of conscious sheep. The recovery of the infused solution was 75–90%, suggesting a localized change in the ionic composition and osmolality restricted to a relatively small area in the cerebrospinal fluid (CSF). Sodium and potassium excretion and urine flow were studied before, during, and after perfusion of 200, 150, and 100 mM Na-CSF. Localized perfusion in the anterior dorsal third ventricle (AD3V) of 200 mM Na-CSF caused an increase in sodium and potassium excretion, in urine flow, and a decrease in free water clearance. Perfusion of 200 mM Na-CSF at the other three perfusion sites, i.e., anterior ventral third ventricle, posterior dorsal third ventricle, and posterior ventral third ventricle, did not influence sodium excretion and urine flow. Perfusions with 150 and 100 mM Na-CSF did not cause any change in sodium, potassium excretion, or urine flow at any of the four perfusion sites. These results suggest that sensors sensitive to changes of sodium concentration are located close to the ventricular surface in the anterior dorsal part of the third cerebral ventricle. When stimulated with increased sodium concentration they will initiate increased sodium excretion.
Autoregulation of renal blood flow and glomerular filtration rate in the pregnant rabbit
Authors: Woods L. L. , Mizelle H. L. , Hall J. E.
Published: December 2017

Our purpose was to determine whether renal autoregulatory capability is retained in pregnancy despite the marked renal vasodilation that occurs at this time. Renal blood flow and glomerular filtration rate (GFR) were measured in anesthetized pregnant (22–27 days gestation) and nonpregnant rabbits during step reductions in renal perfusion pressure from control (100 +/- 3 mmHg) to 50 mmHg. Control renal blood flow and GFR were significantly higher in pregnant animals, averaging 65 +/- 5 and 13.1 +/- 1.1 ml/min, respectively, compared with 50 +/- 5 and 9.4 +/- 1.2 ml/min in nonpregnant rabbits. Filtration fraction was also significantly elevated in pregnant animals (0.33 +/- 0.02 vs. 0.27 +/- 0.01 in nonpregnant rabbits). During step reductions in renal perfusion pressure, renal blood flow was well autoregulated down to approximately 70 mmHg in both nonpregnant and pregnant animals, falling by only 9 +/- 4 and 12 +/- 5%, respectively. Likewise, GFR was also well autoregulated, falling by 10 +/- 2 and 8 +/- 3% in nonpregnant and pregnant animals, respectively, when perfusion pressure was reduced from 90 to 70 mmHg. These results suggest that renal autoregulation is preserved in pregnancy despite the fact that the renal circulation is already markedly vasodilated.
Peripheral and brain tissue catecholamine content in intact and anti-NGF-treated fetal sheep
Authors: Schuijers J. A. , Walker D. W. , Browne C. A. , Thorburn G. D.
Published: December 2017

Fetal lambs were treated with a single dose of anti-mouse nerve growth factor (anti-NGF) at 80 days gestational age. The catecholamine content of tissues was determined at 135 days gestational age. There was a reduction of either norepinephrine, epinephrine, or both, in the thymus, thyroid, atrium (but not ventricle), lung, liver, kidney, and jejunum when compared with age-matched control fetuses. The spleen, ileum, colon, and the adrenal glands were not affected by anti-NGF. In treated fetuses there was a reduction in catecholamine content of the thalamus, hypothalamus, hippocampus, medulla, cerebellum, and cervical spinal cord. These results show that some tissues are sensitive to, and some are refractory to, the action of anti-NGF at 80 days gestation. Also the results suggest that NGF may play a role in the development of catecholamine-containing neurons within the central nervous system.
Hematological measurements in rats flown on Spacelab shuttle, SL-3
Authors: Lange R. D. , Andrews R. B. , Gibson L. A. , Congdon C. C. , Wright P. , Dunn C. D. , Jones J. B.
Published: December 2017

Previous studies have shown that a decrease in red cell mass occurs in astronauts, and some studies indicate a leukocytosis occurs. A life science module housing young and mature rats was flown on shuttle mission Spacelab 3 (SL-3), and the results of hematology studies of flight and control rats are presented. Statistically significant increases in the hematocrit, red blood cell counts, and hemoglobin determinations, together with a mild neutrophilia and lymphopenia, were found in flight animals. No significant changes were found in bone marrow and spleen cell differentials or erythropoietin determinations. Clonal assays demonstrated an increased erythroid colony formation of flight animal bone marrow cells at erythropoietin doses of 0.02 and 1.0 U/ml but not 0.20 U/ml. These results agree with some but vary from other previously published studies. Erythropoietin assays and clonal studies were performed for the first time.
Cardiac muscle ultrastructure and cyclic AMP reactions to altered gravity conditions
Authors: Mednieks M. I. , Fine A. S. , Oyama J. , Philpott D. E.
Published: December 2017

Morphological and biochemical analyses of heart muscle of rats subjected to microgravity on Spacelab 3 (SL-3) flight and rats born and reared under increased gravity (1.7 G) conditions were compared with 1-G controls. Electronmicroscopic studies showed an increase in the number of lipid droplets and in areas of glycogen storage. Distribution changes of microtubules and cytoskeletal elements from both SL-3 and 1.7-G groups were observed. The high Km cyclic AMP phosphodiesterase activity was lower (P less than 0.05) in SL-3 heart muscle, and low Km activity was lower in 1.7-G males but was unaltered in females. Cyclic AMP-dependent protein kinase (cA-PK) activity was decreased in subcellular fractions of heart muscle of SL-3 animals. Recompartmentalization of cA-PK activity occurred in particulate tissue fraction of 1.7-G animals (70.3% of total for 1.7 G vs. 35.9% for controls). Phosphorylation of endogenous low-mobility proteins increased in SL-3 heart-soluble fractions. Photoaffinity labeling (18 h, 4 degrees C) decreased in type II cA-PK regulatory (R) subunits in both SL-3 and in 1.7-G male heart tissue particulate fractions. The 1.7-G female heart R subunit distribution did not differ from controls. These findings indicate that in heart muscle altered gravity conditions influenced physiological reactions similar to catecholamine-induced receptor-mediated hormonal responses.
Salivary gland ultrastructure and cyclic AMP-dependent reactions in Spacelab 3 rats
Authors: Mednieks M. I. , Hand A. R.
Published: December 2017

Environmental stimuli influencing catecholamine levels induce changes in cyclic AMP-dependent reactions and cell morphology in the rat parotid. Responses of salivary glands to spaceflight were determined by measurement of cyclic AMP-mediated reactions in fresh-frozen salivary glands and by microscopic evaluation of ultrastructure in fixed parotid glands. Decreased cell-free protein phosphorylation occurred in parotid glands in three of five flight animals. Protein kinase activity ratios were decreased in the soluble and increased in the particulate fractions of Spacelab 3 (SL-3) rat sublingual glands, compared with ground controls. Biochemical analyses show that effects of space flight on salivary glands are similar to those induced experimentally by physiological manipulation or alteration of catecholamine levels. Morphological evaluation of three SL-3 rat parotid glands showed increased numbers of lysosomes, autophagic vacuoles containing degenerating secretory product, and accumulation of lipid droplets. Since these animals lost weight, consistent with disruption of food and water consumption, morphological changes may in part be due to decreased masticatory stimulation, as occurs with reduced food intake or a liquid diet. The observed changes may reflect physiological responses of the gastrointestinal and autonomic systems to effects of spaceflight.
Sinoaortic denervation in the nonhuman primate
Authors: Bishop V. S. , Shade R. E. , Haywood J. R. , Hamm C.
Published: December 2017

There is considerable controversy as to whether removal of baroreceptor input by sinoaortic deafferentation leads to a sustained hypertension in quadripeds. Because of the importance of the baroreflex during postural changes, the effects of baroreceptor denervation may be even more profound in the primate. In this study, six adult male baboons (Papio anubis) were maintained on a tether system to examine the acute and sustained effects of aortic and combined carotid sinus and aortic baroreceptor deafferentation. Mean arterial pressure (MAP) averaged over 24 h increased from 86 +/- 4.0 to 105 +/- 5.5 mmHg after aortic denervation. One week after sinoaortic deafferentation, arterial pressure rose to 129 +/- 12.9 mmHg and then receded to 97 +/- 4.4 mmHg at 4 wk postdenervation. The lability of arterial pressure (measured as the mean of the standard deviations over 24 h) did not change with aortic denervation but increased at 1 and 4 wk after complete baroreceptor denervation. These studies indicate that baroreceptor deafferentation in the primate results in an acute increase in arterial pressure, the lability of arterial pressure, and heart rate. However, by 4 wk postdenervation, the level and lability of arterial pressure are decreased but remain significantly elevated.
Does myoglobin contribute significantly to diffusion of oxygen in red skeletal muscle?
Authors: Covell D. G. , Jacquez J. A.
Published: December 2017

We have examined the role of myoglobin to facilitate O2 diffusion to active mitochondria in skeletal muscle by constructing computer-simulation experiments. Steady-state mitochondrial O2 consumption under different conditions of supply partial pressure of O2 (PO2) in a system with and without myoglobin were examined for a one-dimensional slab of tissue. O2 consumption by mitochondria was saturable with the mitochondria located in bands at uniform intervals throughout the tissue. Under these conditions, myoglobin provides a measurable increase in O2 transport for supply PO2 below 10 Torr and diffusion lengths expected for skeletal muscle fibers. We conclude that under circumstances where hypoxia lowers PO2 below 10 Torr that myoglobin begins to provide a measurable increase in O2 delivery to mitochondria.
Proglumide, a cholecystokinin antagonist, increases gastric emptying in rats
Authors: Shillabeer G. , Davison J. S.
Published: December 2017

Injection of cholecystokinin (CCK) reduces food intake and delays gastric emptying. We have previously shown that endogenous CCK also reduces food intake. This may be achieved by a delay in gastric emptying. We investigated the role of CCK in gastric emptying by inhibiting the actions of CCK released by a meal, using a CCK antagonist, proglumide. We postulated that inhibition of CCK should induce an increase in gastric emptying. Gastric emptying was determined in rats by a marker dilution technique using direct gastric intubation. Proglumide (150 mg/kg) significantly accelerated emptying of liquid food by 12.8% (P less than 0.005, n = 12) when injected intraperitoneally following a food preload. Proglumide injected before feeding was ineffective. Oral proglumide, which inhibited gastrin-stimulated acid secretion, was also ineffective. We concluded that proglumide increased gastric emptying by acting on a factor released by the preload, and since proglumide is a specific antagonist, this factor was probably CCK. Therefore CCK may play a physiological role in the regulation of gastric emptying.
Effect of neuropeptide Y on ingestive behaviors in the rat
Authors: Morley J. E. , Levine A. S. , Gosnell B. A. , Kneip J. , Grace M.
Published: December 2017

Neuropeptide Y (NPY) is a potent stimulator of food and water intake in rats. NPY still increases food intake even after a 2-h delay in access to food after central injection. When two injections of NPY are given 2 h apart, the second injection produced a substantial increase in food intake. This suggests that tolerance to the NPY effect does not develop after a single injection of NPY. NPY increases moving and exploration in the absence of food when rats are in their home environment but not when tested in a novel environment. Following administration of NPY, rats preferred a high-carbohydrate diet over a high-fat or high-protein diet. Microinjections of NPY showed that active sites included the anterior ventromedial nucleus, paraventricular nucleus of the hypothalamus, and the posterior lateral hypothalamus. NPY was neither additive nor synergistic when coadministered with norepinephrine. Whereas norepinephrine-induced feeding was inhibited by adrenalectomy and vagotomy, these maneuvers had no effect on NPY-induced food intake. This provides further evidence that NPY does not exert its effects on food intake through an alpha-adrenergic mechanism. The effects of NPY on food intake were attenuated by peripherally administered bombesin and centrally administered corticotropin-releasing factor and calcitonin. Cholecystokinin failed to inhibit NPY-induced feeding. NPY did not alter circulating glucose levels. These studies provide further insights into the role of NPY as a stimulator of ingestive behaviors.
Forebrain contribution to sympathetic nerve discharge in anesthetized cats
Authors: Huang Z. S. , Gebber G. L. , Barman S. M. , Varner K. J.
Published: December 2017

We tested the hypothesis that the forebrain is responsible for a component of basal sympathetic nerve discharge (SND) in the anesthetized cat. For this purpose integrated postganglionic inferior cardiac SND and blood pressure were measured before and after serial transections of the midbrain at stereotaxic planes A3 and AP0. In the first series of experiments on baroreceptor-denervated cats anesthetized with alpha-chloralose, A3 transection significantly reduced SND to 62 +/- 7% of control. Blood pressure was reduced 33 +/- 4 mmHg. SND and frontal-parietal cortical activity were temporally related prior to A3 transection in many of these animals. Recovery of SND and blood pressure to control levels occurred within 30 min after A3 transection. A second midbrain transection at AP0 failed to affect SND and blood pressure at this time. This observation suggests that the effects of A3 transection were due to the loss of a component of SND of forebrain origin rather than to generalized trauma. The effects of A3 transection were not attributable to cataleptic anesthesia with alpha-chloralose, since SND and blood pressure were significantly reduced by midbrain transection in baroreceptor-denervated cats anesthetized with diallylbarbiturate-urethan. A3 transection also reduced SND and blood pressure in some baroreceptor-innervated cats. Finally, medial diencephalic ablation prevented the effects of A3 transection. We conclude that the forebrain is responsible for a significant component of sympathetic tone in anesthetized cats. Recovery from the loss of this component, however, occurs rapidly even in animals deprived of their compensatory baroreceptor reflex mechanisms.
Renal brush-border Na+-H+ exchange activity in the aging rat
Authors: Kinsella J. L. , Sacktor B.
Published: December 2017

Amiloride-sensitive Na+-H+ exchange activity in brush-border membrane vesicles isolated from male rat proximal tubules was decreased in the senescent rat (24 mo) compared with the young adult (6 mo). There was no significant loss in Na+-H+ exchange activity in the kidneys of animals between 6 and 18 mo of age. Amiloride-insensitive Na+ uptake and the rate of pH gradient dissipation were not altered during aging. The decrease in sodium-dependent phosphate transport preceded the decline in Na+-H+ exchange activity by at least 6 mo. Sodium-dependent glucose transport was not significantly altered during aging. Thus various renal plasma membrane transport functions were affected differently in the aging rat. The decrease in Na+-H+ exchange activity during aging contrasted with the increase in exchange activity reported previously in acute ablation models of chronic renal failure.
Polyunsaturated lipid diet lengthens torpor and reduces body temperature in a hibernator
Authors: Geiser F. , Kenagy G. J.
Published: December 2017

Membrane lipids of vertebrate animals that tolerate cold are high in polyunsaturated fatty acids. Because the lipid composition of cellular membranes in mammals can be experimentally altered by diet, we investigated whether a diet rich in polyunsaturated fatty acids would lengthen bouts of torpor and reduce the minimum body temperature in hibernating chipmunks (Eutamias amoenus) compared with a diet rich in saturated fatty acids. Animals on the highly unsaturated diet showed significantly longer bouts of torpor, lower minimum body temperatures, and lower metabolic rates than those on a saturated diet. Animals on a control diet were intermediate. These dietary adjustments apparently influence the control of body temperature by the central nervous system, which results in a modification of the pattern of torpor. The observations also suggest a role of nutritional ecology in hibernation.
Ventral medullary surface inputs to cervical sympathetic respiratory oscillations
Authors: Van Lunteren E. , Mitra J. , Prabhakar N. R. , Haxhiu M. A. , Cherniack N. S.
Published: December 2017

To examine the effects of focally cooling three areas (rostral, intermediate, and caudal) of the ventral medullary surface (VMS) on respiratory oscillations in cervical sympathetic and phrenic nerve activity, 12 cats were anesthetized, vagotomized, paralyzed, and artificially ventilated with 7% CO2 in O2. Cooling the intermediate area from 37 to 20 degrees C significantly reduced the magnitude of respiratory oscillations in both cervical sympathetic activity (P less than 0.001) and phrenic activity (P less than 0.001). Graded cooling of all three areas caused graded reductions in sympathetic respiratory-related activity that were comparable to the reductions in phrenic activity. The magnitude of the reductions in sympathetic respiratory oscillations was greatest for the intermediate area, followed in order by the caudal and rostral areas. Eight cats also underwent graded VMS cooling while ventilated with 3% CO2 in O2 and 100% O2. At each level of inspired CO2, graded cooling resulted in graded reductions in respiratory oscillations in sympathetic activity; conversely, at each medullary temperature, graded increases in inspired CO2 caused graded increases in cervical sympathetic respiratory activity. These results suggest that all three areas of the VMS influence respiratory oscillations in cervical sympathetic activity, although to different extents.
Role for the median preoptic nucleus in centrally evoked pressor responses
Authors: O'Neill T. P. , Brody M. J.
Published: December 2017

Recent evidence suggests an important role for the median preoptic nucleus (MnPO) in cardiovascular responses evoked by angiotension II (ANG II). We therefore planned to determine whether selective inactivation of this nucleus would produce deficits in pressor responsiveness to centrally administered ANG II and carbachol. Chronic disruption of MnPO by electrolytic lesion produced pressor deficits to centrally administered ANG II and carbachol but did not change resting arterial pressure. In addition, blockade of neuronal activity in MnPO produced by the microinjection of the local anesthetic lidocaine reversibly attenuated pressor responses to these agents without producing any change in resting arterial pressure. The microinjection of ANG II itself into sites in which lidocaine blocked ANG II pressor responses had no effect on arterial pressure but did produce drinking. These data suggest that the MnPO, although not acting as a receptor site for the pressor effect of ANG II, plays an important role in mediating the pressor response evoked by centrally administered ANG II and carbachol.
Afferent vagal stimulation, vasopressin, and nitroprusside alter cerebrospinal fluid kinin
Authors: Thomas G. R. , Thibodeaux H. , Margolius H. S. , Webb J. G. , Privitera P. J.
Published: December 2017

The effects of afferent vagal stimulation, cerebroventricular vasopressin, and intravenous nitroprusside on cerebrospinal fluid (CSF) kinin levels, mean arterial pressure (MAP), and heart rate (HR) were determined in anesthetized dogs in which a ventriculocisternal perfusion system (VP) was established. Following bilateral vagotomy, stimulation of the central ends of both vagi for 60 min significantly increased MAP and CSF perfusate levels of kinin and norepinephrine (NE). MAP was increased a maximum of 32 +/- 4 mmHg, and the rates of kinin and NE appearance into the CSF perfusate increased from 4.2 +/- 1.4 to 22.1 +/- 6.9 and from 28 +/- 5 to 256 +/- 39 pg/min, respectively. A significant correlation was found between CSF kinin and NE levels in these experiments. In other experiments the addition of arginine vasopressin to the VP system caused a significant increase in CSF perfusate kinin without affecting MAP or HR. Intravenous infusion of nitroprusside lowered MAP without affecting kinin levels in the CSF. However, on cessation of nitroprusside infusion, CSF kinin increased significantly in association with the return in MAP to predrug level. Collectively the data are consistent with the hypothesis that central nervous system kinins have some role in cardiovascular regulation, and furthermore that this role may involve an interaction between brain kinin and central noradrenergic neuronal pathways.
Substrate and O2 fluxes during rest and exercise in a high-altitude-adapted animal, the llama
Authors: Hochachka P. W. , Mommsen T. P. , Jones J. H. , Taylor C. R.
Published: December 2017

Llamas were trained to exercise on a treadmill at graded speeds. O2 uptake values at rest, at modest exercise (ME, 0.58 m/s), and at heavy exercise (HE, 1.84 m/s) were 0.069, 0.297, and 0.594 ml O2 X kg-1 X s-1. Corresponding values for cardiac output were 1.64, 4.39, and 6.85 ml X kg-1 X s-1. Palmitate, glucose, and lactate replacement rates (Ra values) were determined at these varying work rates using a single-bolus injection of 14C- or 3H-labeled metabolites, two at a time. Ra values for palmitate, glucose, and lactate at rest were 6.2, 61.4, and 36.1 mumol X kg-1 X min-1, respectively. During ME, the Ra values for glucose and palmitate increased about twofold but showed no further increase when exercise intensity was increased about twofold. In contrast to these results, Ra values for lactate increased much more with increasing work rate. A combination of increased perfusion (increased cardiac output) and increased lactate availability (increased plasma concentration) could account for the lactate Ra data. During prolonged ME, the Ra for lactate decreased because lactate availability decreased; concurrently, both the plasma free fatty acid availability and the Ra values for palmitate greatly increased. Because O2 carrying capacity is low in the llama (as in all high-altitude-adapted mammals), a given level of exercise required exaggerated increases in cardiac output (and hence in perfusion rates of working muscles). As a result, the flux rates of palmitate, glucose, and lactate through the plasma compartment could readily account for O2 flux rates even at relatively high sustainable rates of exercise.
Optimal experiment design for nonlinear models subject to large prior uncertainties
Authors: Walter E. , Pronzato L.
Published: December 2017

Classical experiment design generally yields an experiment that depends on the value of the parameters to be estimated, which are, of course, unknown. Assuming that the model parameters belong to a population with known statistics, we propose to take the a priori parameter uncertainty into account by optimizing the mathematical expectation of a functional of the Fisher information matrix. This optimization is performed with a stochastic approximation algorithm that makes robust experiment design almost as simple as classical D-optimal design. The resulting methodology is applied to the choice of measurement times for multiexponential models.
Micropuncture study of proximal tubule pH in avian kidney
Authors: Laverty G. , Alberici M.
Published: December 2017

Transepithelial potentials (PD) and pH gradients were measured by in vivo micropuncture in superficial proximal tubules of anesthetized European starlings. The average PD for 46 tubules was 2.24 +/- 1.17 mV (mean +/- SD), lumen negative. Only a single lumen-positive potential was recorded, even though late proximal segments are accessible to micropuncture. Proximal luminal pH, measured with single-barrel pH-sensitive microelectrodes, averaged 7.62 +/- 0.26. The pH of peritubular blood, also measured with microelectrodes, was 7.58 +/- 0.15. Correction of the luminal pH for the average PD resulted in a value of 7.58. A few measurements made with double-barrel microelectrodes indicated a pH in proximal tubules of 7.65 +/- 0.08 with a PD of -3.32 +/- 1.47 mV. Thus there appears to be no transepithelial pH gradient across these tubules. On the other hand, pH measurements of cortical collecting ducts averaged 6.40 +/- 0.37, indicating significant acidification in more distal segments. Starlings made acutely acidotic by HCl infusion had significantly reduced arterial and renal cortical pH values, but there was still no significant pH gradient across the proximal tubule. In conclusion, these superficial "reptilian-type" proximal tubules do not appear to have the capacity to maintain a pH gradient. Based on this and on the lack of lumen-positive chloride diffusion potentials, there appears to be no early proximal preferential bicarbonate reabsorption by these nephrons.
Thyroid hormone depresses antioxidant enzyme maturation in fetal rat lung
Authors: Sosenko I. R. , Frank L.
Published: December 2017

The surfactant system and antioxidant enzyme system of the lung have chronologically similar developmental patterns, and the maturation of both systems is accelerated by glucocorticoid hormones. To investigate whether thyroid hormone might also stimulate the development of the antioxidant enzyme system as well as the surfactant system, we injected pregnant rats with triiodothyronine (T3) or diluent. Fetal T3 offspring demonstrated significantly elevated T3 levels, had significantly increased lung tissue disaturated phosphatidylcholine (DSPC) and total phospholipid content, yet had significantly decreased activities of three lung antioxidant enzymes (AOE) (superoxide dismutase, catalase, and glutathione peroxidase). When dexamethasone was administered in combination with T3, fetuses demonstrated increases in lung DSPC content but decreases in AOE of magnitude equivalent to or greater than that seen with T3 alone. These findings indicate that thyroid hormone affects surfactant and AOE development in opposite ways and may have potentially harmful as well as beneficial effects on different aspects of lung development.
Vasopressin release in sheep following various degrees of rehydration
Authors: Blair-West J. R. , Gibson A. P. , Sheather S. J. , Woods R. L. , Brook A. H.
Published: December 2017

Restriction of the water intake of sheep to 0.5 1/day for 7-9 days increases plasma arginine vasopressin (pAVP), and voluntary rehydration causes a rapid fall in pAVP with no change in plasma osmolality. The extent of that inhibition of AVP release was assessed by comparing the decline of pAVP after drinking with pAVP disappearance curves obtained in the same sheep after stopping a constant infusion of AVP at 0.5 micrograms/h, which increased pAVP to the dehydration level. The fall in pAVP after drinking was almost identical with the disappearance curve showing that AVP release was almost completely inhibited during the 2-3 min taken for the sheep to drink 3-5 liters to satiate themselves. The response seemed, therefore, to be cued before the intake reached the satiating volume. When dehydrated sheep drank only 0.5 or 1.0 liter, in 30 s or less, pAVP again fell rapidly but only to a minimum approximately 15 min after drinking. The pAVP was unaltered in dehydrated sheep presented with water but denied access to it. Thus satiation was not necessary for rapid inhibition of AVP release after drinking, but satiation was necessary for this inhibition to be maintained. The initial inhibition was associated with falls in hematocrit and plasma total protein but not plasma osmolality. This isosmolar dilution occurred even in sheep that saw but were denied access to the water and suggests a shift of fluid from the extravascular space.
Enhancement of quiet sleep in rabbit neonates by muramyl dipeptide
Authors: Davenne D. , Krueger J. M.
Published: December 2017

Muramyl peptides that induce excess slow-wave sleep have been isolated from urine and brain. A synthetic analogue to those substances, muramyl dipeptide (MDP, N-acetylmuramyl-L-alanyl-D-isoglutamine), was found to induce prolonged increases in slow-wave sleep and to increase electroencephalographic (EEG) delta-wave activity. MDP is also pyrogenic, although this activity can be separated from its somnogenic activity. To further investigate the somnogenic actions of MDP, neonatal rabbits were used in the present study. Intraperitoneal injection of 100 micrograms/kg MDP induced differential somnogenic and pyrogenic effects; from postnatal days 7-9, MDP increased duration of quiet sleep (QS, the precursor of adult slow-wave sleep) and decreased active sleep (AS) as judged by behavioral criteria. These animals were not febrile during the period of enhanced QS, nor did MDP alter EEG delta-wave activity at this age. From postnatal days 10-15, MDP induced prolonged (6 h) increases in duration of QS; both behavioral and EEG criteria were used at this age to determine duration of QS and AS. Maximum MDP-induced effects occurred during the 2nd h, with a parallel increase in amplitudes of EEG delta-wave activity. At this age, MDP also elicited monophasic fevers and inhibition of AS, with maximum effects observed during hours 3-4 postinjection. After postnatal day 16, MDP-induced somnogenic and febrile responses were similar to those observed in adult rabbits. We conclude that the mechanisms responsible for behavioral sleep states are responsive to a sleep-promoting substance early in ontogenesis.
Sensory innervation of white adipose tissue
Authors: Fishman R. B. , Dark J.
Published: December 2017

The presumption that sensory information does not arise from white adipose tissue was reevaluated using the neuroanatomical tracer, "true blue." Fluorescent cell bodies were observed in dorsal root ganglia of rats after tracer was implanted into inguinal or dorsal subcutaneous fat depots. Sensory information from adipose tissue may play an important role in the regulation of regional and total body fat mass.
Increased fetal secretion of ACTH and cortisol by arginine vasopressin
Authors: Faucher D. J. , Laptook A. R. , Parker C. R. , Porter J. C. , Rosenfeld C. R.
Published: December 2017

In the fetus, arginine vasopressin (AVP) has been considered a "stress" hormone with primarily cardiovascular effects. In adult animals, AVP also has substantial endocrine effects, e.g., acting as a corticotropin-releasing factor, an effect not clearly demonstrated in the fetus. Therefore we examined this action of AVP in fetal sheep [135 +/- 1 (SE) days gestation] during a 30-min vasopressin infusion (12 mU/min) while monitoring mean arterial pressure (MAP) and heart rate (HR). Blood samples were obtained before, 15 and 30 min during, and 30 and/or 60 min after the infusion. During vasopressin infusion (n = 11), MAP increased (P less than 0.01), whereas HR fell (P less than 0.01). Plasma AVP increased from 2.32 +/- 0.22 to 84 +/- 6.8 and 89 +/- 10 microU/ml (P less than 0.001), whereas adrenocorticotropin (ACTH) rose from 18.0 +/- 2.4 to 27.7 +/- 3.7 and 43.4 +/- 8.0 pg/ml (P less than 0.05) and cortisol from 1.81 +/- 0.36 to 3.48 +/- 0.56 and 3.97 +/- 0.57 micrograms/dl (P less than 0.005) at 15 and 30 min, respectively. Although neither basal nor AVP-induced ACTH increases changed over the period of gestation studied, base-line cortisol concentrations and the absolute rise in ACTH-stimulated cortisol release increased as gestation progressed, demonstrating increased adrenal sensitivity to ACTH. As in adults, AVP stimulates fetal pituitary secretion of ACTH, providing evidence for another role for AVP in fetal adaptation.
Further evidence implicating prostaglandin E2 in the genesis of pyrogen fever
Authors: Coceani F. , Lees J. , Bishai I.
Published: December 2017

Conscious cats were used to study the effects of endotoxin and interleukin 1 (IL 1) on levels of prostaglandin (PG) E2 and thromboxane (TX) B2 (the stable TXA2 byproduct) in cerebrospinal fluid (CSF) from the third ventricle. Pyrogens were given intravenously or intraventricularly and prostanoids were measured by radioimmunoassay. PGE2 was normally less abundant than TXB2 (mean, 37 vs. 528 pg/ml), and its level increased severalfold during the sustained fever following intravenous endotoxin (bolus) or IL 1 (bolus plus infusion). PGE2 elevation preceded the fever and was maintained thereafter. Likewise, intraventricular pyrogens promoted PGE2 formation, and their effect was also manifest during the latent period of the fever. The PGE2 metabolite, 13,14-dihydro-15-keto-PGE2, was not measurable in CSF from either afebrile or febrile animals. Basal content of PGE2, on the other hand, was higher in animals pretreated with probenecid (30 mg/kg ip or iv; 50 or 100 micrograms ivt), confirming the importance of transport processes in removing prostanoids from brain. Unlike PGE2, TXB2 levels did not change during the fever to intravenous endotoxin. TXB2 rose instead in response to intraventricular endotoxin, although the elevation did not extend beyond fever uprise. Furthermore, a TXA2 analog (ONO-11113;2 or 4 micrograms ivt) had inconsistent effects on body temperature, while a TXA2 antagonist (ONO-11120;2 micrograms ivt) did not interfere with endotoxin fever. These findings strongly support a causative role for PGE2 in the onset and progression of pyrogen fever. No evidence of a similar role was obtained for TXA2.
Decreased hexokinase activity in paraventricular nucleus of adult SHR and renal hypertensive rats
Authors: Krukoff T. L.
Published: December 2017

Metabolic activity was assessed in the brains of spontaneously hypertensive rats (SHR) using the histochemical hexokinase (HK) technique and photodensitometric analysis. Of eight regions known to play a role in cardiovascular regulation, only the paraventricular nucleus of the hypothalamus (PVH) exhibited alterations in HK activity. Significantly lower levels of HK activity in SHR than in control Sprague-Dawley and Wistar-Kyoto rats were measured in both the parvo- and magnocellular divisions of the PVH. No differences in HK activity were found in the anterior hypothalamic nucleus, posterior hypothalamic nucleus, supraoptic nucleus, subfornical organ, central nucleus of the amygdala, or the medial nucleus of the tractus solitarius of SHR. Similar results were obtained in renal hypertensive rats; furthermore, a positive correlation was found between levels of arterial pressure and densitometric readings. These latter results strongly suggest that metabolic alterations in the PVH of SHR are directly related to the increases in arterial pressure and are not due to the genetic makeup of SHR. In light of studies by others, the data from the present study have been interpreted to suggest that the decreases in metabolic activity in the PVH of the adult SHR are the result of a central attempt to bring the level of the arterial pressure down to normal levels and not to the altered activity of a region that might be acting to keep arterial pressure elevated.
Maximum heart rate responses to exercise and isoproterenol in the trained rat
Authors: Bolter C. P. , Atkinson K. J.
Published: December 2017

Male rats were assigned to light (C) or strenuous (T) running programs. Both groups ran at 30 m/min, 8% elevation. Over 16 wk, T and C completed 2,939 +/- 72 and 507 +/- 7 min (mean +/- SE). In a graded running test, maximum exercise heart rates for T and C were 542 +/- 7 and 554 +/- 6 beats/min (P greater than 0.05). Heart rates elicited by maximum effective concentrations of isoproterenol (ISO) in vivo and in vitro were 483 +/- 8 and 489 +/- 11 beats/min for T and 499 +/- 5 and 502 +/- 5 beats/min for C (no difference between groups or treatments). A lower heart rate was recorded in T for both resting (353 +/- 7 vs. 373 +/- 4 beats/min) and in vitro intrinsic states (231 +/- 22 vs. 299 +/- 22 beats/min) (P less than 0.05 for both conditions). The difference between maximum ISO-stimulated and maximum exercise heart rates was attributed to a temperature difference. In a separate group of lightly trained rats, ISO was administered intravenously during hard exercise when heart rate approached exercise maximum. Heart rate after ISO did not increase beyond the maximum heart rate observed in a control run. It was concluded that the maximum chronotropic response to sympathetic stimulation can be elicited during hard exercise and that maximum exercise heart rate reflects this limit rather than a saturation of cardiac sympathetic activity.
Fetal thoracic duct lymph flow response to intravascular saline infusion
Authors: Brace R. A.
Published: December 2017

The left thoracic lymph duct was catheterized at the base of the neck in the sheep fetus at 123-136 days of gestation, and the lymphatic catheter was connected to a jugular vein catheter so that the lymph could return to the fetus. Lymph flow was studied 5 days after catheter implantation in the unanesthetized fetus. Basal fetal thoracic duct lymph flow rate per unit body weight averaged three times adult sheep values. After an infusion of 20 ml/kg of warmed isotonic saline into a fetal vein over 5 min, lymph flow rate increased significantly to 161 +/- 15% of control, with a peak at 8 min after termination of the infusion, and flow declined thereafter. The increased lymph volume above baseline values over 30 min averaged 5.7% of the infused volume and is similar to the adult response. Plasma and lymph protein concentrations decreased as did the lymph-to-plasma protein concentration ratio. The latter is opposite to what occurs in the adult under the same conditions. Thus the present study shows that even though the fetus has a much higher basal thoracic duct lymph flow rate than the adult, the responsiveness of the fetal lymphatic system to intravascularly infused saline is similar to that of the adult. The decrease in the lymph-to-plasma protein concentration ratio suggests that there may be differences between fetal and adult vascular-interstitial-lymphatic protein kinetics.
CCK-8 decreases food intake and gastric emptying after pylorectomy or pyloroplasty
Authors: Smith G. P. , Falasco J. , Moran T. H. , Joyner K. M. , Gibbs J.
Published: December 2017

Specific binding sites for cholecystokinin (CCK) in the gastrointestinal tract of the adult rat are limited to the gastroduodenal region and are concentrated in the circular muscle of the pyloric sphincter. To determine the relationship of these pyloric muscle binding sites to the inhibition by CCK of food intake and of gastric emptying, these inhibitory effects of CCK were investigated in rats that had the pyloric sphincter surgically removed or that had the pyloric sphincter contractile mechanism damaged by a pyloroplasty procedure. CCK-8 decreased food intake and gastric emptying significantly in rats after pylorectomy or pyloroplasty. This demonstrates that an intact pyloric sphincter is not necessary for these inhibitory effects in rats. Because we found autoradiographic evidence for CCK receptors near the gastroduodenal anastomosis, however, the results suggest either that these receptors mediated the inhibition of food intake and emptying by CCK-8 or that these effects depend on CCK receptors in other locations.