bluuebunny/crossref_metadata_2025 huggingface dataset:
kappa-Opioid antagonist improves cellular bioenergetics and recovery after traumatic brain injury
Authors: Vink R. , Portoghese P. S. , Faden A. I.
Published: December 2017

Treatment with opioid receptor antagonists improves outcome after experimental brain trauma, although the mechanisms underlying the protective actions of these compounds remain speculative. We have proposed that endogenous opioids contribute to the pathophysiology of traumatic brain injury through actions at kappa-opioid receptors, possibly by affecting cellular bioenergetic state. In the present study, the effects of the kappa-selective opioid-receptor antagonist nor-binaltorphimine (nor-BNI) were examined after fluid percussion brain injury in rats. Metabolic changes were evaluated by 31P magnetic resonance spectroscopy; the same animals were subsequently followed over 2 wk to evaluate neurological recovery. Nor-BNI, administered intravenously as a 10 or 20 mg/kg bolus at 30 min after injury, significantly improved neurological outcome at 2 wk posttrauma compared with controls. Animals treated with nor-BNI showed significantly greater recovery of intracellular free magnesium concentrations and cytosolic phosphorylation potentials during the first 4 h after injury compared with saline-treated controls. The improvement in cytosolic phosphorylation potential was significantly correlated to neurological outcome. These data support the hypothesis that kappa-opioid receptors mediate pathophysiological changes after traumatic brain injury and that the beneficial effects of opioid-receptor antagonist may result from improvement of posttraumatic cellular bioenergetics.
Spontaneously hypertensive rat: lymphoid depression is age dependent and mediated via a mononuclear cell subpopulation
Authors: Pascual V. H. , Oparil S. , Eldridge J. H. , Jin H. , Bost K. L. , Pascual D. W.
Published: December 2017

Immune dysfunction has been reported in spontaneously hypertensive rats (SHR), particularly in mature animals with established hypertension. The current study examined the time course of development of immune dysfunction and defined its cellular basis in male SHR and control normotensive Wistar-Kyoto rats (WKY). Mitogen-induced proliferative responses in lymphoid cells obtained from induced proliferative responses in lymphoid cells obtained from SHR thymus and spleen before (age 4 wk) and during the development of (ages 8 and 12 wk) hypertension and in age-matched normotensive WKY were monitored. A 50% reduction in concanavalin A (Con A)-induced proliferative responses was seen in SHR thymocytes compared with those of WKY at 12 wk only, suggesting differences in immature T-cell populations. Con A-induced T-cell proliferative responses in splenocytes also differed between strains: greatest (as much as 8-fold) decreases were found in 12-wk-old SHR. Similar findings were obtained in splenocytes stimulated with lipopolysaccharide (LPS), indicating differences in B-cell function. Mononuclear cells depleted of their adherent cell population were prepared from SHR and WKY at 12+ wk of age and assayed for their proliferative responses to LPS and Con A. The remaining nonadherent mononuclear cells of SHR had proliferative responses equal to or greater than those of WKY. Further, when SHR splenic mononuclear cells were allowed to adhere to plastic, and the adherent fraction was co-cultured with either SHR G-10 nonadherent or unfractionated SHR splenic mononuclear cells, proliferative responses were suppressed by as much as 88%.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanism of decreased cardiac output during ANP infusion in conscious anephric dogs
Authors: Mizelle H. L. , Gaillard C. A. , Manning R. D. , Hall J. E.
Published: December 2017

Atrial natriuretic peptide (ANP) may decrease cardiac output (CO) by lowering circulating blood volume (BV) or by altering the vasculature in a manner that would decrease venous return. The purpose of this study was to determine the role of decreased BV in mediating the decrease in CO during acute infusion of ANP. BV was measured by dilution of 51Cr-labeled red blood cells in seven trained conscious splenectomized dogs studied after unilateral (UNX) and total (TNX) nephrectomy. BV, hematocrit (Hct), CO, mean arterial pressure (MAP), and total peripheral resistance (TPR) were determined during a 90-min control period and 270 min of infusion of ANP (20 ng.kg-1.min-1 iv). In UNX dogs, ANP decreased BV from 60.9 +/- 1.4 to 58.6 +/- 1.4 ml/kg and increased Hct from 39.3 +/- 1.8% to 41.1 +/- 1.8% (P less than 0.05). MAP was not changed and CO fell to a low that was 86 +/- 2% of control (P less than 0.05) 240 min after starting ANP. TPR increased significantly during ANP infusion. All variables returned to control after ANP was stopped. In the same dogs studied 24 h after TNX, MAP averaged 111 +/- 5 mmHg during control and did not change during ANP infusion. CO fell to a low of 82 +/- 3% of control (P less than 0.05) after 120 min of infusion and remained reduced until after the ANP was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)
Sucrose-induced lipid, glucose, and insulin elevations, microvascular injury, and selenium
Authors: Lockwood M. K. , Eckhert C. D.
Published: December 2017

Injury to microvessels caused by the chronic consumption of sucrose can be prevented by selenium (Se). The objective of this study was to determine the temporal sequence of changes in serum triglycerides, total cholesterol, glucose, and insulin induced by sucrose and their relationship to Se status and microvascular injury. Two groups of 24 Wistar rats were fed ad libitum diets in which the entire carbohydrate was either corn starch or sucrose. Two other groups were fed identical diets supplemented with 0.1 micrograms Se/g. At 6, 8, and 10 mo, eight rats from each group were fasted for 12 h and had blood taken. Rats were then given a glucose tolerance test and killed, and their retinal microvessels were evaluated for injury. After 6 mo, sucrose-fed rats had elevated triglycerides and total cholesterol. Abnormal glucose clearance and hyperinsulemia developed after 8 mo. Evidence of microvascular injury became apparent after 10 mo. These changes did not occur in rats provided the starch-based diets, and microvascular injury did not develop in the sucrose-fed rats provided supplemental Se. Glutathione peroxidase activity was normal in all groups throughout the 10-mo experiment. These results chronicle the sucrose-induced systemic insult and show that the protective effect of Se does not occur by diminishing this insult to the microvessels.
Relationship of adipocyte size to hyperphagia in developing male obese Zucker rats
Authors: Vasselli J. R. , Fiene J. A. , Maggio C. A.
Published: December 2017

In growing male obese Zucker rats, hyperphagia reaches a maximum or “breakpoint” and declines at an earlier age with high fat than with chow-type diets. A serial adipose tissue biopsy technique was used to correlate changes of retroperitoneal adipocyte size and feeding behavior in 5- to 7-wk-old male lean and obese rats fed laboratory chow or a 35% fat diet until 30 wk of age. Although chow-fed groups had significantly greater cumulative intake, fat-fed groups had significantly greater body weight gain, retroperitoneal depot weight, and adipocyte number. Mean adipocyte size increased continuously in chow-fed groups but decreased over weeks 20-30 in fat-fed groups, reflecting increased adipocyte number. In fat-fed obese rats, hyperphagia reached a breakpoint at 11 wk and disappeared by 13 wk. In chow-fed obese rats, hyperphagia reached a breakpoint at 15-16 wk and disappeared by 19 wk. Biopsy samples revealed that adipocyte size of fat-fed obese rats was already close to maximal at 10 wk (1.12 micrograms lipid), while that of chow-fed obese rats only approached maximal at 20 wk (0.81 microgram lipid). At these time points, lipoprotein lipase activity paralleled adipocyte size. These data indicate that the duration of the growing obese rat's hyperphagia coincides with adipocyte filling and suggest the existence of feeding stimulatory and inhibitory signals from adipose tissue.
Triacylglycerol: an important pool of essential fatty acids during early postnatal development in rats
Authors: Cunnane S. C. , Chen Z. Y.
Published: December 2017

Developmental changes in the content and composition of major organ lipid pools are not well known. Our objective was to assess quantitatively the changes in lipids, particularly those containing long-chain fatty acids, in the placenta and the brain, liver, and carcass of the fetal and suckling rat. Pregnant dams were killed at days 15, 18, and 21 (term) of pregnancy and the placentas and fetuses removed and analyzed; suckling rats were killed at days +3, +6, and +9 of lactation. Whereas the long-chain fatty acid content of the phospholipids (mg/g) of the fetal or suckling rat remained relatively constant from day 18 of pregnancy to day +9 of lactation, long-chain fatty acids in triacylglycerols increased from prenatal values by 10- to 12-fold during the first 9 postnatal days. Prenatally, triacylglycerol accounted for no more than 32% of total whole body essential fatty acids (day 21), but postnatally this increased to 81-88%. From day 21 to day +9, the proportion of n-6 and n-3 essential fatty acids within the total triacylglycerol pool of the suckling rat increased 71 and 317%, respectively. We conclude that in the suckling rat, triacylglycerol is quantitatively the most important source of essential fatty acids during at least the first 9 days of life.
Quantitative analysis on odor intensity and quality of optical isomers in turtle olfactory system
Authors: Taniguchi M. , Kashiwayanagi M. , Kurihara K.
Published: December 2017

No systematic electrophysiological study on differences in odor intensity and quality between optical isomers has been carried out. In the present study, we measured the turtle olfactory bulbar responses to six pairs of highly pure optical isomers and compared the differences in odor intensity and quality between the optical isomers. The results obtained indicated that with all odorants tested, there was no difference in odor threshold and intensity in the whole concentration range examined between optical isomers. The difference in odor quality of optical isomers was evaluated by a quantitative cross-adaptation method in which odorant concentration was varied. The degree of cross adaptation between optical isomers greatly varied with species of odorants. The rank order of the magnitude of the differences in odor quality between optical isomers was carvone greater than beta-citronellol greater than menthol greater than hydroxycitronellal greater than citronellal greater than limonene.
Prolonged stable hypothermia: effect on blood gases and pH in rats and ground squirrels
Authors: McArthur M. D. , Jourdan M. L. , Wang L. C.
Published: December 2017

Richardson's ground squirrels [body temperature (Tb) 7 degrees C] survive prolonged stable hypothermia for three times as long as do rats (Tb 19 degrees C) (72 vs. 24 h). We have examined the changes in blood gases and acid-base state to assess whether these contribute to this difference in survival time. None of the variables (measured at ambient temperature of 25 degrees C) differed significantly between rats and ground squirrels before hypothermic induction. During cooling, neither hematocrit nor plasma lactate changed significantly, but arterial and venous PO2 and PCO2 increased and arterial and venous pH decreased in both groups. During prolonged hypothermia, hematocrit increased significantly in rats (58.8 +/- 1.7% at 24 h) but not in ground squirrels (39.1 +/- 1.0% at 72 h). Both species maintained stable arterial blood gases but showed decreased venous PO2; arterial and venous pH decreased significantly with time in both species in conjunction with increased plasma lactate. These patterns of decreased venous PO2 and increased plasma lactate suggest that reduced tissue oxygenation occurs during hypothermia. This happens earlier in rats at a Tb of 19 degrees C than in ground squirrels at a Tb of 7 degrees C, possibly as a result of increased hematocrit in hypothermic rats. Remedial measures directed at improving tissue O2 delivery may therefore prolong the hypothermic survival of rats.
Fever, tumor necrosis factor, and interleukin-6 in young, mature, and aged Fischer 344 rats
Authors: Foster K. D. , Conn C. A. , Kluger M. J.
Published: December 2017

The purpose of this study was to compare the febrile responses of Fischer 344 rats of different ages [young (3-5 mo), mature (12-15 mo), and aged (24-27 mo; n = 8)] to two psychological stress paradigms, cage switch and exposure to an open field, as well as to injection of lipopolysaccharide (LPS). In addition, the cytokines tumor necrosis factor-alpha (TNF) and interleukin-6 were also measured in the plasma of these rats at 90 min postinjection with LPS. There was no significant difference among groups in febrile responses to switching their cages. Exposure to an open field for 30 min resulted in a smaller rise in temperature in the aged rats (0.62 degree C) than in the young rats (1.26 degrees C). This difference disappeared if rats were exposed to an open field for 60 min. Injection of LPS led to fevers that developed at a slower rate in aged rats than in the mature groups. The peak fevers, however, were not different. The activity of interleukin-6 90 min after injection of LPS was higher in aged rats (297,858 U/ml) than in young (17,462 U/ml) and mature rats (28,819 U/ml). TNF levels were also higher in aged rats (16,380 U/ml) compared with young (574 U/ml) and mature rats (36 U/ml). We conclude that although the magnitude of the febrile response is not different among rats of different ages, the rise in body temperature occurs slower in aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Pinniped splenic volumes
Authors: Ponganis P. J. , Kooyman G. L. , Sartoris D. , Jobsis P.
Published: December 2017

Splenic volume was measured by computerized axial tomography in three harbor seals (Phoca vitulina) and two California sea lions (Zalophus californianus). Volumes ranged from 228 to 679 ml, representing 0.8-3.0% of calculated percentage body mass. Despite possible variation in the state of splenic contraction during the examination, these values are in the upper range of reported mammalian splenic volumes (as % of body mass). This reinforces the pinniped splenic erythrocyte storage concept.
Preoptic norepinephrine-induced hypothermia is mediated by alpha 2-adrenoceptors
Authors: Quan N. , Xin L. , Ungar A. L. , Blatteis C. M.
Published: December 2017

We have shown previously that norepinephrine (NE) microdialyzed into the preoptic area of conscious guinea pigs evokes a fall in core temperature (Tco) that is mediated by a reduction in metabolic rate. To identify the adrenoceptor subtype(s) involved in this effect, we microdialyzed intrapreoptically various adrenergic agonists or antagonists singly or in combinations. Tco and ear skin temperatures of the animals were monitored throughout the experiments. alpha 1-, beta-, beta 1-, and beta 2-agonists and antagonists did not induce significant Tco changes. Although the alpha 2-antagonists yohimbine (Yoh) and rauwolscine (Rau) did not have thermal effects per se, the alpha 2-agonist clonidine evoked dose-dependent Tco falls that were abolished by codialyzed Yoh and Rau. The microdialysis of NE evoked, as before, a 0.7 +/- 0.2 degrees C Tco fall; it was abolished by the codialyzed alpha-antagonist phentolamine, Yoh, and Rau but not by the beta-antagonist propranolol. No adrenoceptor agonist induced changes in ear skin temperature. These results indicate that the hypothermizing effect of intrapreoptically microdialyzed NE is achieved by a reduction in metabolic heat production, mediated by alpha 2-adrenoceptors.
Rapid stimulation of intestinal D-glucose transport in teleosts by 17 alpha-methyltestosterone
Authors: Hazzard C. E. , Ahearn G. A.
Published: December 2017

Effects of 17 alpha-methyltestosterone (MT) on transmural transport of 0.5 mM D-[3H]-glucose across upper intestine of the herbivorous teleost, Oreochromis mossambicus, were examined using modified Ussing chambers containing a physiological saline. Treatment tissues were preincubated with MT on the serosal surface for 30 min, while control tissues were incubated with an equivalent volume of 70% ethanol. Stimulation of mucosal-to-serosal D-glucose flux (Jm----s) by MT was dose dependent with maximal transport enhancement at 15 ng MT/ml saline (215% of control) and inhibition of sugar transfer occurring at 50 ng MT/ml (60% of control). Hormone treatment (15 ng MT/ml) significantly (P less than 0.05) increased net transmural D-glucose flux (Jnet; control = 0.36 +/- 0.084, MT = 0.75 +/- 0.130 nmol.cm-2.min-1) as a result of enhancing Jm----s (control = 0.52 +/- 0.048; MT = 0.91 +/- 0.078 nmol.cm-2.-1) without having a significant effect on the serosal-to-mucosal flux (Js----m). Mucosal addition of 1 mM phloridzin significantly (P less than 0.05) reduced glucose transport Jm----s in the presence and absence of MT, without altering the respective Js----m fluxes. Serosal addition of the hormone led to significant increases in Jm----s and Jnet in less than 20 min. This rapid intestinal response to MT was abolished by serosal addition of 1 mM colchicine, and therefore an increased insertion rate of performed glucose carriers is a suggested mechanism of hormone action.
Renal interstitial hydrostatic pressure during verapamil-induced natriuresis
Authors: Granger J. P. , Solhaug M. J.
Published: December 2017

Infusion of calcium antagonists results in significant increases in sodium excretion, an effect that is exacerbated in hypertensive animals. The mechanism responsible for the increase in sodium excretion has not been elucidated. The purpose of this study was to determine the role of renal interstitial hydrostatic pressure (RIHP) in mediating increases in sodium excretion produced by the calcium antagonist verapamil. Changes in renal hemodynamics and electrolyte excretion were examined in response to an intrarenal infusion of verapamil (100 micrograms/min) in normal dogs and in dogs with angiotensin II-induced hypertension. Infusion of verapamil in normal dogs increased renal blood flow by 18% and had no effect on glomerular filtration rate. Renal vascular resistance and filtration fraction both decreased in response to verapamil. Absolute (5.1 +/- 2.3 to 176 +/- 45.8 mueq/min) and fractional excretion of sodium (0.21 +/- 0.13 to 7.36 +/- 3.12%) also increased significantly. Despite renal vasodilation, the natriuresis was not associated with significant increases in RIHP (6.4 +/- 0.9 to 5.8 +/- 0.9 mmHg). Infusion of verapamil into dogs with angiotensin II hypertension resulted in a natriuresis (4.2 +/- 1.6 to 338.7 +/- 78.3 mueq/min) that was much greater than under normal conditions. Although the renal vasodilation was significantly higher in the angiotensin II-hypertensive dogs, the enhanced natriuresis in these animals was not associated with increases in RIHP. The results of this study indicate that increases in RIHP are not responsible for the natriuresis produced by verapamil in normal or angiotensin II-hypertensive dogs.
Pressor effect of posterior hypothalamic stimulation is enhanced in pregnant rats
Authors: Hines T. , Porter J. P.
Published: December 2017

In contrast to the attenuated pressor response to intravenous angiotensin II (ANG II) in rat pregnancy, the response to intracerebroventricular ANG II is not blunted. To test whether this difference was due to enhanced effects of sympathetic nervous system activation, blood pressure, heart rate, and renal and mesenteric blood flow were measured in conscious term-pregnant and age-matched virgin rats during electrical stimulation of the posterior hypothalamus and during intravenous infusion of norepinephrine (NE). The pressor responses to endogenous NE release by hypothalamic stimulation were significantly greater (P less than 0.05) in pregnant rats at 10, 15 and 20 Hz. In contrast, the pressor response to exogenous NE was significantly blunted in gravid animals. These differences were not associated with significant differences in renal or mesenteric vascular resistance changes. We conclude that the lack of an attenuated response to intracerebroventricular ANG II in the pregnant rat can be explained in part by an enhanced pressor effect of sympathetic nervous system activation.
Reproductive organ blood flow measured using radioactive microspheres in diestrous and estrous mice
Authors: Dowell R. T. , Gairola C. G. , Diana J. N.
Published: December 2017

Blood flow is a primary mechanism controlling reproductive organ functions. In the present study, radioactive microsphere techniques were adapted to measure ovarian, uterine, and vaginal blood flow levels in C57BL mice. Anesthetized animals were tracheostomized and the left carotid artery was cannulated. The heart was exposed and 113Sn-labeled spheres (15 microns size, 2 microCi, 0.1 ml) were injected via the left ventricle. Reference sample was obtained by carotid artery blood "free flowing" into a tared microfuge tube for 1 min. The animal was killed, and selected tissues were excised for weighing and radioactivity measurement to determine flow. Absence of differences in flow levels (ml.min-1.g-1) to paired nonreproductive organs (adrenals and kidneys) validated the procedure. Blood flow levels were significantly higher in the ovaries, but not in the uterus and vagina of estrous mice vs. diestrous mice. Comparison of left vs. right ovaries suggested consistent blood flow distribution during diestrus. Ovarian blood flow level is enhanced during estrus and, in addition, is highly nonuniform regarding right-left flow distribution. Nonuniform ovarian blood flow distribution in estrous mice leads us to speculate that alternating right-left (i.e. nonuniform) ovulation predominates during each murine estrous cycle.
Methylmercury transport across the blood-brain barrier by an amino acid carrier
Authors: Kerper L. E. , Ballatori N. , Clarkson T. W.
Published: December 2017

The mechanism by which methylmercury (MeHg) crosses the blood-brain barrier was examined in the rat. Previous studies demonstrated that intravenous injection of L-cysteine with MeHg accelerates MeHg uptake into brain. Since the complex of MeHg with L-cysteine is structurally similar to L-methionine, a substrate for the L (leucine-preferring) amino acid transport system, this carrier may be involved in MeHg uptake. To examine this hypothesis, the rapid carotid infusion technique was used in the anesthetized rat. The concentration dependence of 203Hg uptake into brain after injection of Me203Hg-L-cysteine complex was nonlinear, exhibiting characteristics of saturable transport (apparent Michaelis constant 0.39 mM, vmax 33 nmol.min-1.g-1). A slower, nonsaturable uptake was seen after MeHg-L-cysteine uptake was inhibited by methionine and the amino acid analogue 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH), an L system substrate, but not by alpha-methylaminoisobutyric acid, an alanine-preferring system substrate. Furthermore, L-[14C]methionine transport was inhibited by MeHg-L-cysteine but not by MeHgCl. There was a significant amount of uptake of 203Hg when injected as Me203Hg-glutathione, and this was inhibited by L-methionine and BCH but not D-methionine. S-ethylglutathione also inhibited 203Hg uptake after administration as Me203Hg-glutathione but had no effect on Me203Hg-L-cysteine uptake. These results suggest that MeHg may enter the brain as a cysteine complex via the L system and that plasma MeHg-glutathione serves as a source of MeHg-cysteine.
Identification of carotid vascular receptors that control adrenal catecholamine secretion in dogs
Authors: Engeland W. C. , Zippe C. D. , Gann D. S.
Published: December 2017

The role of carotid sinus and thyrocarotid mechanoreceptors in the reflex control of adrenal medullary function was assessed in anesthetized dogs with adrenal vein catheters. Dogs underwent carotid sinus, thyrocarotid junction, combined carotid sinus and thyrocarotid junction, or sham denervation. On the day after surgery, catecholamine secretion was measured after carotid occlusion proximal to the thyrocarotid junction, cervical vagotomy, and repeat carotid occlusion, each separated by 90 min. After combined carotid denervation, baseline norepinephrine secretion was increased, resulting in a decreased epinephrine-to-norepinephrine ratio. Carotid occlusion before vagotomy did not change the secretion of catecholamines or the epinephrine-to-norepinephrine ratio. After sham carotid denervation, acute vagotomy did not affect catecholamine secretion. However, after denervation of the carotid sinus or thyrocarotid junction, vagotomy resulted in small increases in catecholamine secretion without changing the epinephrine-to-norepinephrine ratio; the magnitude of the response was augmented after combined denervation. At 90 min after vagotomy in dogs with intact carotid baroreceptors, carotid occlusion increased adrenal secretion of catecholamines and decreased the epinephrine-to-norepinephrine ratio. After denervation of carotid sinus or thyrocarotid junction receptors, carotid occlusion increased secretion of catecholamines without changing the epinephrine-to-norepinephrine ratio; the response was abolished by combined denervation. These results show that both carotid sinus and thyrocarotid receptors contribute to the adrenomedullary response to carotid occlusion and to acute vagotomy. Also, reduction in the activity of carotid sinus and thyrocarotid junction receptors chronically (by denervation) or acutely (by carotid occlusion) results in preferential secretion of norepinephrine over epinephrine.
Maturational differences in acetazolamide-altered pH and HCO3 of choroid plexus, cerebrospinal fluid, and brain
Authors: Johanson C. E. , Parandoosh Z. , Dyas M. L.
Published: December 2017

The carbonic anhydrase inhibitor acetazolamide is useful for analyzing ion transport, pH regulation, and fluid formation in developing central nervous system. We used the 14C-labeled dimethadione technique to measure alterations in steady-state pH, and to estimate the HCO3 concentration [HCO3], in choroid plexus (CP), cerebrospinal fluid (CSF), and cerebral cortex of 1- and 3-wk-old Sprague-Dawley rats treated with acetazolamide or probenecid. These drugs can suppress transport of HCO3 and other anions in some cells, consequently altering intracellular pH. In 1-wk-old infant rats whose CSF secretory process is incompletely developed, 1 h of acetazolamide treatment did not significantly change CP intracellular pH or [HCO3]. However, in 3-wk-old rats, in which the ability of CP to secrete ions and fluids is almost fully developed, acetazolamide caused marked increases in CP cell intracellular pH and [HCO3]. In contrast, acetazolamide-induced alkalinization was not observed in CSF or cerebral cortex of the 1- and 3-wk-old animals. The other test agent, probenecid (an inhibitor of anion transport but not of carbonic anhydrase), did not alter the pH of any region at any age investigated. Overall, the results are interpreted in light of developmental changes in carbonic anhydrase and previous findings from kinetic analyses of ion-translocating systems in CP. Acetazolamide may interfere with a CP apical membrane HCO3 extrusion mechanism not fully operational in infant rats.
Food deprivation and refeeding in the camel (Camelus dromedarius)
Authors: Dahlborn K. , Benlamlih S. , Zine-Filali R. , Gueroulali A. , Hossaini-Hilali J. , Oukessou M.
Published: December 2017

Camels thrive in arid and semiarid areas, although food and water frequently are scarce. However, the mechanisms enabling camels to withstand food deprivation are poorly understood. In this study four female camels were totally deprived of food for 4 days. Their body weight decreased by 6%. Food deprivation caused no change in total plasma protein concentration in the camel, indicating that no alterations in plasma volume occurred. When the first meal was withheld water intake was unchanged. Next day the camels showed signs of hydration with a decreased plasma Na+ concentration and an increased excretion of diluted urine. In the afternoon water intake decreased. Urine K+ excretion fell the first day and urine volume and Na+ excretion from the third day. No activation of the renin-angiotensin-aldosterone system (RAAS) was observed. Plasma and urine urea concentration increased during food deprivation. Plasma glucose concentration and plasma cortisol and thyroxine levels did not change. Body temperature decreased during food deprivation. After refeeding, total plasma proteins increased temporarily by 12%, and a threefold increase in RAAS was seen, implying that both plasma volume and RAAs changed rapidly. Our results show that fluid balance was only slightly affected in the food-deprived camel. We suggest that strategies for the camel to endure food deprivation include maintenance of plasma volume and glucose concentration and a lowering of the body temperature.
Medullary pathways for adrenocorticotropic hormone and vasopressin secretion in rabbits
Authors: Gieroba Z. J. , Fullerton M. J. , Funder J. W. , Blessing W. W.
Published: December 2017

We determined, in urethan-anesthetized rabbits, whether pharmacological alteration of neuronal function in the ventrolateral medulla oblongata, including the A1 area, and in the nucleus tractus solitarii (NTS), alters plasma adrenocorticotropic hormone (ACTH) and vasopressin and whether inhibition of neuronal function in the ventrolateral medulla impairs the secretion of ACTH normally observed in response to hemorrhage or constriction of the inferior vena cava. We also tested whether the increase in plasma ACTH and vasopressin after pharmacological inhibition of neuronal function in the NTS is dependent on a pathway that synapses in the A1 area of the ventrolateral medulla. Activation of the A1 area with bicuculline increased both ACTH and vasopressin. Inhibition of the NTS with muscimol increased levels of both hormones, as did hemorrhage and constriction of the inferior vena cava. Inhibition of neuronal function within the A1 area with muscimol eliminated the secretion of vasopressin but did not significantly alter the secretion of ACTH, obtained by injecting muscimol into the NTS. Injection of muscimol into the A1 area eliminated the secretion of both ACTH and vasopressin in response to constriction of the inferior vena cava and, in the case of vasopressin, in response to hemorrhage. Although hemorrhage-initiated secretion of ACTH was significantly reduced by injection of muscimol into the A1 area, it was not completely eliminated by these injections or by injections of muscimol into a more rostrocaudally extensive region of the medulla oblongata. We conclude that the net output from the NTS tonically inhibits secretion of both ACTH and vasopressin, reflecting tonic baroreceptor tone. For vasopressin, the pathway from the NTS to the hypothalamus is dependent on a synapse in the A1 area. For ACTH, there are pathways to the hypothalamus that do not synapse in the A1 area, but neurons in this region do have an excitatory effect on secretion of ACTH.
Central nervous system catecholamine content and norepinephrine release after AV3V ablation
Authors: Van Huysse J. W. , Bealer S. L.
Published: December 2017

Electrolytic ablation of the periventricular tissue surrounding the anteroventral third cerebral ventricle (AV3V-X) results in immediate increases in norepinephrine release in the paraventricular hypothalamic nucleus/anterior hypothalamus (P/A) and in the dorsomedial medulla (DM) and depletion of norepinephrine and epinephrine throughout the brain. The present study determined whether catecholamine depletion and/or altered norepinephrine release persisted after recovery from the acute effects of AV3V-X. Fourteen to eighteen days after surgery, catecholamine concentrations throughout the brain and norepinephrine release in the P/A and DM during hemorrhage were measured in control-operated and AV3V-X rats. AV3V-X decreased epinephrine content only in the midbrain, increased norepinephrine only in the cortex, and produced no differences in central nervous system dopamine. Hemorrhage-induced norepinephrine release was significantly greater in the P/A of AV3V-X rats than in control animals, whereas norepinephrine release in the DM increased equally in both groups. Thus AV3V-X does not result in chronic global central nervous system catecholamine depletion and enhances norepinephrine release in the P/A during hemorrhage.
CCK-A receptors mediate the effect of cholecystokinin on vasopressin but not on cortisol in pigs
Authors: Parrott R. F. , Forsling M. L.
Published: December 2017

Bolus intravenous injections of cholecystokinin (CCK) octapeptide induce a rapid rise in plasma vasopressin and a later increase in cortisol in the prepubertal pig. To determine whether these endocrine responses involve CCK-A or CCK-B receptors, this experiment investigated the effect of CCK (1 microgram/kg) in pigs (n = 7) pretreated with the CCK-A antagonist L 364718 (70 microgram/kg) or the CCK-B antagonist L 365260 (10 ng/kg and 10 micrograms/kg). The animals were prepared with jugular vein catheters and given the antagonist vehicle, L 364718, or L 365260 10 min before administration of CCK or saline. Analysis of hormone concentrations in blood samples taken 2, 5, 10, and 20 min after the second injection indicated that an abrupt rise in vasopressin, detectable within 2 min of CCK administration, occurred after vehicle or L 365260 pretreatment but not when CCK was preceded by L 364718. In contrast, the rise in plasma cortisol that was observed approximately 15 min after CCK injection was not prevented by either antagonist. Thus peripherally administered CCK induces vasopressin release by CCK-A receptor activation, in agreement with its inhibitory effect on food intake in this species. However, the effect of CCK on cortisol secretion does not appear to involve either CCK-A or CCK-B receptors.
Geometry of blood-tissue exchange in bat flight muscle compared with bat hindlimb and rat soleus muscle
Authors: Mathieu-Costello O. , Szewczak J. M. , Logemann R. B. , Agey P. J.
Published: December 2017

We investigated the relationship between capillary-to-fiber geometry and muscle aerobic capacity by comparing the bat flight muscle (pectoralis muscle), i.e., an ultimate case of extreme O2 demand in a mammalian skeletal muscle, with bat hindlimb and rat soleus muscles. At a given sarcomere length (2.1 microns), fiber cross-sectional area was considerably smaller in bat muscles (pectoralis 318 +/- 10 microns 2, hindlimb 447 +/- 35 microns 2) than in rat soleus muscle (2,027 +/- 125 microns 2). Capillary number per fiber cross-sectional area was much greater in bat pectoralis (6,394 +/- 380/mm2) than in bat hindlimb and rat soleus muscle (2,865 +/- 238 and 1,301 +/- 129/mm2, respectively; all values normalized to 2.1-microns sarcomere length). At the same sarcomere length (2.1 microns), the degree of tortuosity and branching of capillaries were significantly greater in bat pectoralis than in bat hindlimb and rat soleus muscle. In bat flight muscle, capillary length per fiber volume was very high (9,025 +/- 342/mm2). It was 2.2- and 5.4-fold larger than in bat hindlimb and rat soleus, respectively. Mitochondria occupied 35.3 +/- 1.2, 16.5 +/- 1.3, and 6.1 +/- 0.9% of the muscle fiber volume in bat pectoralis, hindlimb, and rat soleus muscles, respectively. There was a strong correlation between capillary length (as well as capillary surface) per fiber volume and mitochondrial volume density in all muscles. Considering capillary supply and mitochondrial volume on an individual fiber basis, we found that 1) the number of capillaries around a fiber was linearly related to mitochondrial volume per micron length of fiber in the muscles but that 2) capillary surface per fiber surface, at given mitochondrial volume per micron length of fiber, was about twice as large in bat pectoralis as in rat soleus muscle, whereas in bat hindlimb it was intermediate between that in bat pectoralis and that in rat soleus muscle. This was due to the differences in fiber size (rat soleus greater than bat muscles) and capillary-to-fiber ratio (bat pectoralis greater than hindlimb) between the muscles. It is notable that in the bat, the substantially greater O2 transfer capacity of the flight muscle compared with hindlimb was achieved by increasing the size of the capillary-to-fiber interface, i.e., capillary-to-fiber surface, via an increase in capillary number rather than by substantially reducing fiber size.
Underfeeding and body weight regulation in normal-weight young men
Authors: Heyman M. B. , Young V. R. , Fuss P. , Tsay R. , Joseph L. , Roberts S. B.
Published: December 2017

The mechanisms of energy regulation invoked by moderate dietary restriction were investigated in seven healthy young men of normal body weight leading unrestricted lives. Following a baseline period of weight maintenance, subjects were underfed by 806 +/- 162 (mean +/- SE) kcal/day for 21 days. Changes in total energy expenditure (TEE) and resting energy expenditure (REE) and subsequent voluntary nutrient intakes were measured. The REE, averaged for fasting and fed states, decreased during underfeeding by 100 +/- 29 kcal/day (P less than 0.01). TEE decreased nonsignificantly by 296 +/- 170 kcal/day, equivalent to an average of 37% of the decrease in energy intake. Body energy stores were estimated to decrease by 510 +/- 172 kcal/day (P less than 0.03), thus compensating for 63% of the dietary energy deficit on average. Voluntary energy intake following dietary restriction increased above the initial amount required for body weight maintenance, was proportional to the weight loss during underfeeding (P less than 0.03), and was associated with a rapid regain of weight lost during underfeeding. These results indicate that energy balance is regulated by adaptive variations in both energy intake and energy expenditure in normal-weight young men leading unrestricted lives but do not support the hypothesis that energy-wasting mechanisms contribute substantially to body energy regulation.
Effects of hypoxia and ambient temperature on gaseous metabolism of newborn rats
Authors: Mortola J. P. , Dotta A.
Published: December 2017

Whole body metabolic rate was measured by open-flow respirometry in 2-day-old rats at ambient temperatures (Ta) between 40 and 15 degrees C, changed at a rate of 0.5 degrees C/min, during normoxia or hypoxia (10% inspired O2). In normoxia, the thermoneutral range was found to be very narrow, at around 33 degrees C, suggesting a limited effectiveness in the mechanisms controlling heat dissipation. At lower or higher Ta, metabolism was at first increased; this increase could be maintained for at least 30 min at 30 and 35 degrees C, i.e., slightly below or above thermoneutrality, but it was not maintained at lower Ta. The metabolic response to Ta was not sufficient to maintain body temperature (Tb). In hypoxia, at all Ta, oxygen consumption (VO2) was consistently less than in normoxia and was linearly related to Ta (Q10 approximately 1.4). The rat's specific heat was 4 J.g-1.degrees C-1, and the time constant of passive heat exchange was 2.2 +/- 0.5 min; from these values it was calculated that the normoxic VO2 of the 2-day-old rat could be per se sufficient to maintain Tb of 35-36 degrees C at Ta of 33 degrees C, while at lower Ta the metabolic response could not be adequate to maintain Tb. In hypoxia, Tb was directly dependent on Ta.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of hypotension and hyperosmolality on vasopressin and ACTH responses to hypoglycemia in conscious dogs
Authors: Raff H. , Papanek P. E. , Cowley A. W.
Published: December 2017

The purpose of these studies was, first, to determine whether hypertonic saline (HS) infusion or nitroprusside (NiPr)-induced hypotension augments the vasopressin (AVP) and adrenocorticotropic hormone (ACTH) responses to insulin (Ins)-induced hypoglycemia and, second, to determine whether neurohypophysectomy could attenuate the augmentation. Conscious, male dogs (n = 8) underwent two different types of experiments. In the first, Ins was preceded by either a 30-min infusion of normal saline (control) or HS to raise plasma osmolality and AVP. HS augmented the AVP response but diminished the ACTH response to Ins. In the second group of experiments, Ins was preceded by a controlled decrease in mean arterial pressure using NiPr, which led to an increase in AVP and ACTH. The initial ACTH and AVP response to Ins was augmented by NiPr, but this early augmentation was not sustained. Neurohypophysectomy attenuated the early augmentation of the ACTH response to Ins by NiPr, but did not alter the final ACTH level achieved. We conclude that HS augmented the AVP but inhibited the ACTH response to Ins probably because of expansion of plasma volume. Concomitant hypotension led to an augmentation of the early but not sustained AVP and ACTH response to Ins. Neurohypophysectomy eliminated this augmentation, suggesting a role for AVP from the neural lobe in the early ACTH response to combined hypotension and Ins-induced hypoglycemia.
Intestinal nutrient transport during ontogeny of vertebrates
Authors: Buddington R. K.
Published: December 2017

Patterns of transporter development are known for 12 species of vertebrates (2 fish, 1 amphibian, 1 bird, and 8 mammals), ranging from early gestation to adulthood. Although transporters for some nutrients (amino acids and some sugars) appear before the onset of external feeding, species differ in when and which transporters appear. Postnatal changes in the activities of different transporters are twofold: corresponding with shifts in the composition of a species' evolutionary diet, and the need to absorb ever-increasing quantities of food for growth and metabolism. The mechanisms responsible for the age-related shifts in rates of transport include changes in the densities, distribution, and types of transporters for specific nutrients and changes in the physiochemical characteristics of the intestinal brush-border membrane. The signals that trigger the age-related changes originate from internal preprogrammed sources and external sources, with both acting in concert to mediate intestinal development. Although much more is known for the brush-border hydrolases, recent studies with the pig suggest the ontogenetic development of hydrolases and transporters are regulated independently during early development.
Low-dose near-celiac arterial cholecystokinin suppresses food intake in rats
Authors: Calingasan N. , Ritter S. , Ritter R. , Brenner L.
Published: December 2017

Exogenous cholecystokinin (CCK) suppresses food intake by acting on vagal sensory neurons. However, CCK doses used in behavioral experiments are generally much larger than those necessary to produce electrophysiological changes in vagal afferents. We made automated measurements of liquid food intake before, during, and after infusion of low doses of CCK octapeptide (CCK-8) through a chronic aortic catheter with its tip seated just above the celiac juncture. In parallel experiments, we made similar infusions while collecting blood from the hepatic portal and jugular veins for CCK assay. Injection of 10, 30, 50, and 70 pmol of CCK-8 suppressed feeding in a dose-dependent manner beginning 1 min postinfusion. The lowest dose to produce statistically significant suppression of preinfusion intake was 30 pmol. Infusion of the same CCK-8 doses into the jugular vein did not suppress feeding. Near-celiac injection of 30 pmol of CCK-8 produced systemic plasma CCK concentrations averaging 6.5 +/- 1 pM compared with less than 1 pM after saline injection. These findings show that exogenous CCK, by acting on tissues perfused by the celiac artery, can suppress feeding at doses that 1) are similar to those producing effects on the firing of vagal neurons and 2) do not increase plasma CCK concentrations above postprandial levels.
Development of blood pressure and cardiac reflexes in the frog Pseudis paradoxsus
Authors: Burggren W. W. , Bicudo J. E. , Glass M. L. , Abe A. S.
Published: December 2017

Systemic arterial blood pressure and heart rate (fH) were measured in unanesthetized, unrestrained larvae and adults of the paradoxical frog, Pseudis paradoxus from Sao Paulo State in Brazil. Four developmental groups were used, representing the complete transition from aquatic larvae to primarily air-breathing adults. fH (49-66 beats/min) was not significantly affected by development, whereas mean arterial blood pressure was strongly affected, being lowest in the stage 37-39 larvae (10 mmHg), intermediate in the stage 44-45 larvae (18 mmHg), and highest in the juveniles and adults (31 and 30 mmHg, respectively). Blood pressure was not significantly correlated with body mass, which was greatest in the youngest larvae and smallest in the juveniles. In the youngest larvae studied (stages 37-39), lung ventilation was infrequent, causing a slight decrease in arterial blood pressure but no change in heart rate. Lung ventilation was more frequent in stages 44-45 larvae and nearly continuous in juveniles and adults floating at the surface. Bradycardia during both forced and voluntary diving was observed in almost every advanced larva, juvenile, and adult but in only one of four young larvae. Developmentally related changes in blood pressure were not complete until metamorphosis, whereas diving bradycardia was present at an earlier stage.
Parasympathetic involvement in rapid meal-associated conditioned insulin secretion in the rat
Authors: Strubbe J. H.
Published: December 2017

Blood glucose and plasma insulin concentrations were measured in blood sampled via a cardiac catheter in freely moving rats. To obtain a rapid conditioned cephalic phase of insulin secretion, rats were habituated to one of two feeding schedules. Clock-activated opening of doors in front of the food hopper imposed a feeding schedule of either six meals per day or two meals per day. When the doors were opened in both conditions, insulin increased rapidly during the first minute of feeding in the middle of the light phase. However, when presented an empty food hopper immediately after door opening, only rats in the two meal per day condition showed raised insulin levels and not rats in the six meal per day condition. This response was abolished following pharmacological blockade of nicotinic receptors with hexamethonium and muscarinic receptors with atropine. The present study shows that rapid conditioned insulin secretion can be evoked within one minute by a meal-associated stimulus. These results further indicate that this conditioned insulin secretion is vagally mediated and that its occurrence is dependent on the nature of the feeding schedule.
Ontogeny of fetal hepatic and placental growth and metabolism in sheep
Authors: Vatnick I. , Bell A. W.
Published: December 2017

Ontogeny of fetal hepatic and placental growth and in vitro oxygen consumption (VO2) was investigated in fetal lambs at 75, 100, and 136 days postconception. Fetal hepatic relative weight and placental absolute and relative weights declined during this period. Oxygen consumption per gram dry weight of fetal liver and maternal placenta declined between mid and late gestation while fetal placental VO2 was unchanged. Estimated VO2 of the whole placenta did not change while the estimated total hepatic VO2 increased more than threefold between 75 and 136 days. Total hepatic VO2 was highly correlated with total placental VO2 at 136 days (r = 0.84). The results suggest that the placenta reaches its maximum growth and metabolic capacity before 100 days and possibly at or before midgestation. Changes in hepatic weight-specific total VO2, in addition to the declining relative size of the fetal liver, must contribute to the progressive decline in metabolic rate of the whole fetus during the second half of pregnancy. Correlations between placental and fetal liver weights and metabolic rates suggest the possibility of placental regulation of fetal hepatic growth and metabolism.