bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal development of uncoupling protein, uncoupling protein mRNA, and GLUT4 in adipose tissues of goats
Authors: Trayhurn P. , Thomas M. E. , Keith J. S.
Published: December 2017

Adipose tissues have been characterized in newborn goats on the basis of the presence of the 32,000-M(r) mitochondrial uncoupling protein (UCP) diagnostic of brown fat, and early postnatal developmental changes have been determined. Both internal (perirenal, pericardial, and omental) and subcutaneous (hindlimb and neck regions) adipose tissues in newborn goats contained UCP and are therefore brown fat. The insulin-sensitive glucose transporter, GLUT4, was also present in adipose tissues of newborn goats, implying a potential for insulin-stimulated glucose uptake at birth. UCP was still evident in the perirenal fat of goats at 3 wk of age, but the mitochondrial concentration was only 4%, and the amount per cell a mere 0.2%, of that in the newborn. UCP was not detectable, however, in either the omental or subcutaneous adipose tissue at 3 wk of age and had disappeared from the subcutaneous fat before 2 wk. In contrast to UCP, GLUT4 remained throughout the initial 3 wk of postnatal life. The mRNA for UCP was detected in perirenal adipose tissue of newborn goats, indicating that the gene coding for the protein is being expressed at around birth. UCP mRNA was not, however, detectable in the other fat depots; nor was it evident in the perirenal adipose tissue at > or = 2.5 days of age. It is concluded that the adipose tissues of newborn goats (both internal and subcutaneous) represent brown fat and that there is a rapid transition toward white fat over the first weeks of life. This transition occurs at different rates in different depots but is not markedly faster in goats than in other ruminants.(ABSTRACT TRUNCATED AT 250 WORDS)
Time-dependent phrenic nerve responses to carotid afferent activation: intact vs. decerebellate rats
Authors: Hayashi F. , Coles S. K. , Bach K. B. , Mitchell G. S. , McCrimmon D. R.
Published: December 2017

The objectives were to determine 1) respiratory responses to carotid chemoreceptor inputs in anesthetized rats and 2) whether the cerebellar vermis plays a role in these responses. A carotid sinus nerve was stimulated (20 Hz) with five 2-min trains, each separated by approximately 3 min. During stimulation, respiratory frequency (f), peak amplitude of integrated phrenic nerve activity (integral of Phr), and their product (f x integral of Phr) immediately increased. As stimulation continued, integral of Phr progressively increased to a plateau [short-term potentiation (STP)], but f and f x integral of Phr decreased [short-term depression (STD)] to a value still above control. Upon stimulus termination, integral of Phr progressively decreased but remained above control; f and f x integral of Phr transiently decreased below baseline. After the final stimulation, integral of Phr remained above control for at least 30 min [long-term facilitation (LTF)]. Repeated 5-min episodes of isocapnic hypoxia also elicited STP, STD, and LTF. Vermalectomy lowered the CO2-apneic threshold and eliminated LTF. In conclusion, carotid chemoreceptor activation in rats elicits STP and LTF similar to that in cats; the vermis may play a role in LTF. A new response, STD, was observed.
Hypothalamic peptide regulation of ACTH secretion from sheep pituitary
Authors: Kemppainen R. J. , Clark T. P. , Sartin J. L. , Zerbe C. A.
Published: December 2017

The relative abilities of the hypothalamic peptides corticotropin-releasing factor (CRF), arginine vasopressin (AVP), oxytocin (OT), and angiotensin II (ANG II) to stimulate adrenocorticotropic hormone (ACTH) secretion from cultured sheep anterior pituitary cells were studied. Incubation of cells with CRF, AVP, and OT, but not ANG II, was associated with increased ACTH secretion. CRF and AVP were equally effective in stimulating ACTH release at 0.1 nM, but larger doses of each resulted in distinctly different ACTH secretory patterns. The minimally effective dose of OT was 10 nM; greater doses of this peptide resulted in ACTH secretory responses similar to those measured after addition of AVP. Cotreatment with ANG II did not affect the ACTH-secretory response to CRF, AVP, or OT. These data confirm that AVP is a potent stimulus for ACTH secretion from sheep anterior pituitary in vitro and also show that CRF is effective in low concentrations in releasing ACTH. In contrast, the data do not support a regulatory role for ANG II in stimulating ACTH release directly from sheep corticotroph cells.
Regulatory features of protein synthesis in isolated mitochondria from Artemia embryos
Authors: Kwast K. E. , Hand S. C.
Published: December 2017

Optimal conditions were developed for measuring rates of protein synthesis in isolated mitochondria from encysted embryos of Artemia franciscana to 1) identify the required chemical constituents, 2) assess the influence of extramitochondrial pH on protein synthesis, and 3) investigate potential mechanisms coordinating nuclear and mitochondrial gene expression. Isolation procedures resulted in intact, highly coupled mitochondria [respiratory control ratio = 6.48 +/- 0.43 (SE), n = 21]. Requirements for maximal rates of protein synthesis, measured as incorporation of [3H]leucine (60 microM), included an oxidizable carbon source (10 mM succinate), adenine nucleotides (1.5 mM ADP), phosphate (10 mM), K+ (125 mM), Mg2+ (10 mM), amino acids (0.3 mM of each), sucrose or trehalose (500 mM), EGTA (1 mM), and bovine serum albumin (1 mg/ml). Rates were linear for 60 min at 25 degrees C (r = 0.99). Fluorography of translated products revealed 13 peptides. Previous research has shown that anoxia-induced acidification of intracellular pH (pHi) results in suppression of protein biosynthesis, as judged by cytochrome-c oxidase synthesis. In the present study, mitochondrial protein synthesis was acutely sensitive to external pH, with 80% inhibition observed by lowering pH from 7.5 to 6.8. Thus acidification of pHi may serve as one intracellular signal contributing to a coordinated suppression of both cytoplasmic and mitochondrial protein synthesis during transitions from active to anoxia-induced quiescent states.
Inhibition of nitric oxide synthesis suppresses sleep in rabbits
Authors: Kapas L. , Shibata M. , Kimura M. , Krueger J. M.
Published: December 2017

The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, on spontaneous and interleukin-1 (IL-1)-induced sleep were examined in rabbits. Animals were injected intracerebroventricularly or intravenously during the light phase with vehicle, L-NAME, IL-1, or the combination of L-NAME and IL-1. Injection of L-NAME (5 mg icv and 100 mg/kg iv) suppressed both non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) for 4-6 h. The sleep-suppressive effects are unlikely due to pressor responses to L-NAME because administration of L-NAME (5 mg icv) produced only a transient (3-4 min) slight increase in systemic blood pressure. Injection of IL-1 (20 ng icv) elicited fever, suppressed REMS, and increased NREMS for 6 h. NREMS was suppressed for 3 h after the combined intracerebroventricular injections of 5 mg L-NAME and 20 ng IL-1 and was elevated during postinjection hours 4-6. Administration of IL-1 (30 ng/kg iv) increased NREMS and brain temperature for 2 h. After the combined injection of IL-1 and L-NAME (100 mg/kg), NREMS was significantly suppressed during postinjection hours 1-5. It is not known whether the interactions between the sleep-suppressive effects of L-NAME and the NREMS-promoting effects of IL-1 are specific, being mediated via a common mechanism, or whether they are additive, being mediated via independent mechanisms. The pyrogenic and REMS-suppressive actions of either intracerebroventricularly or intravenously injected IL-1 were not affected by L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)
Reflex regulation of renal nerve activity in cardiac failure
Authors: DiBona G. F. , Sawin L. L.
Published: December 2017

Efferent renal sympathetic nerve activity (ERSNA) is increased in the rat with low-cardiac-output congestive heart failure (CHF; myocardial infarction). Arterial and cardiopulmonary baroreflex control of ERSNA in CHF and control rats was examined. Cardiac index and arterial pressure were lower and total peripheral resistance index, left ventricular end-diastolic pressure, and heart-to-body weight ratio were higher in CHF than in control rats. Increases in left ventricular end diastolic pressure produced by intravenous volume loading failed to increase cardiac index in CHF rats as it did in control rats. Single-unit analysis of aortic baroreceptor nerve activity showed that CHF rats had higher pressure threshold, lower frequency at pressure threshold, and lower gain than control rats. Arterial baroreflex control of ERSNA was attenuated; this was due to diminished gain of the afferent limb while the gain of the central portion of the reflex was normal. Single-unit analysis of vagal nerve activity showed that CHF rats had higher pressure threshold, lower frequency at saturation, and lower gain than control rats. Cardiopulmonary baroreflex control of ERSNA was attenuated; this was due to diminished gain of the afferent limb while the gain of the central portion of the reflex was normal. In the CHF rat, arterial and cardiopulmonary baroreflex control of ERSNA is markedly attenuated because of abnormalities in the periphery at the level of the aortic and cardiopulmonary receptors, respectively, and not in the central nervous system.
Serotonin contracts the isolated rat pylorus via a 5-HT2-like receptor
Authors: Eberle-Wang K. , Braun B. T. , Simansky K. J.
Published: December 2017

Serotonin (5-HT) produced concentration-dependent contractions of the isolated rat pylorus in vitro. Serotonergic contractions were antagonized by the calcium L-channel blocker, diltiazem, but not by tetrodotoxin or atropine. Three drugs that block 5-HT2 receptors, ketanserin, xylamidine, and methysergide, unsurmountably inhibited contractions to 5-HT. In contrast, antagonists of 5-HT3, 5-HT1A/1B, beta-adrenergic, or alpha 1-adrenergic receptors did not alter the response to 5-HT. Devazepide, an antagonist of cholecystokinin (CCK) type-A receptors, blocked contraction produced by CCK-8 but not by 5-HT. Conversely, the 5-HT2 antagonists did not affect CCK-stimulated contraction. These results suggest that 5-HT contracts the pylorus by a 5-HT2-like receptor on muscle and that this response occurs independently of CCKergic receptor mechanisms. Furthermore, the parallel between the overall pharmacological profile for serotonergic contraction of the pylorus and that observed previously for the anorectic action of peripheral 5-HT makes the pylorus a logical candidate for peripheral serotonergic control of feeding.
Weight loss in rats following intraventricular transplants of pancreatic islets
Authors: Richardson R. D. , Ramsay D. S. , Lernmark A. , Scheurink A. J. , Baskin D. G. , Woods S. C.
Published: December 2017

Because of the body's resistance to permanent weight change, obesity remains a major health problem in modern society. It is hypothesized that the regulatory system defending body weight utilizes pancreatic insulin as an indicator of adiposity to the brain. To take advantage of this negative feedback system, we transplanted neonatal (experiment 1) or adult (experiment 2) pancreatic islets containing insulin-secreting cells into the 3rd ventricle of syngeneic Lewis rats. This resulted in an elevation of the insulin signal within the brain and a significant long-term reduction of body weight. Changes in food intake were consistent with the changes of body weight. The implantation of more islets resulted in a greater reduction of body weight, and changes in weight were inversely correlated with the level of insulin achieved in the cerebrospinal fluid. After the two studies were completed, histological examination revealed the presence of insulin-containing cells within the 3rd ventricle and adjacent hypothalamus. These studies suggest that transplanted insulin-secreting cells may provide a potential therapeutic strategy for maintenance of weight loss.
Exchange of purines in human liver and skeletal muscle with short-term exhaustive exercise
Authors: Hellsten-Westing Y. , Kaijser L. , Ekblom B. , Sjodin B.
Published: December 2017

The exchange of purines in liver and active skeletal muscle with short-term exhaustive exercise was investigated. Eight male subjects performed two similar 10-min bouts of exhaustive supine cycling, separated by 75 min of rest. Immediately after termination of the second bout, a tourniquet was applied to the upper part of the thigh for 10 min. After the first bout, the arterial concentration of hypoxanthine and uric acid increased from 4.1 +/- 0.3 (SE) to a peak value of 36.3 +/- 7.9 mumol/l (P < 0.05) and from 335 +/- 23 to a peak value of 421 +/- 28 mumol/l (P < 0.05), respectively. There was a net release of hypoxanthine from the muscle at 12 and 45 min postexercise and an uptake of hypoxanthine and inosine in the liver at 7 and 42 min postexercise. Uric acid was released from the liver at 7 and 42 min after exercise. Before the second exercise bout and at 2 and 10 min after the release of the tourniquet, there was a significant net uptake of uric acid by the muscle. The present study demonstrates that, after strenuous short-term exercise, the main source of plasma hypoxanthine is the muscle, with no net contribution of this purine from the liver. Hypoxanthine in the blood is taken up by the liver where most of it is converted to uric acid. After exercise and a short period of ischemia, uric acid is taken up by the muscle.
Preference and diet type affect macronutrient selection after morphine, NPY, norepinephrine, and deprivation
Authors: Welch C. C. , Grace M. K. , Billington C. J. , Levine A. S.
Published: December 2017

The orexigenic agents morphine, neuropeptide Y (NPY), and norepinephrine (NE) and deprivation have been reported to induce selection of specific macronutrients: fat, carbohydrate (CHO), CHO, and fat, respectively. We utilized analysis of covariance to compensate for the influence of baseline preference on feeding induced by six experimental procedures: morphine, NPY, NE, 24 and 48 h food deprivation, and chronic dietary restriction. Rats received one of two dietary regimens: three macronutrient diets containing CHO, protein, or fat (regimen I) and two nutritionally complete diets that were high CHO or high fat (regimen II). Baseline preference significantly influenced dietary selection after all six experimental procedures studied in regimen I and after NPY, NE, 48 h food deprivation, and chronic dietary restriction in regimen II (covariate P < 0.05). In both dietary regimens, morphine (5 mg/kg) increased consumption of fat, NPY (5 micrograms icv) increased selection of CHO, and consumption of all diets was induced equally after NE injections (20 micrograms icv). After 24 or 48 h food deprivation, animals consumed more fat in regimen I and more CHO diet in regimen II. Restricting food intake by 20% increased fat and protein consumption in regimen I but had no effect in regimen II. Diet selection is affected by prior preference, feeding stimulus, and type of diet choice presented.
Hepatic vagotomy effects on metabolic challenges during parenteral nutrition in rats
Authors: Beverly J. L. , Yang Z. J. , Meguid M. M.
Published: December 2017

During parenteral nutrition (PN) glucoprivic-induced feeding appeared to be neutralized by the oxidation of infused fatty acids. With the use of a latin-square design, the feeding response to 2-deoxy-D-glucose (2-DG) and/or 2-mercaptoacetate (MA) was evaluated in male Sprague-Dawley rats with hepatic branch vagotomy (HV) or sham operations (SO). Rats received continuous infusions of 0.9% saline or PN providing 100% of daily caloric needs (PN-100) for four consecutive days. During PN-100, food intake was stimulated by 2-DG in HV rats and when fatty acid oxidation was simultaneously inhibited by MA. 2-DG-induced hyperglycemia was apparent under all conditions. Lipoprivic-induced feeding and increased plasma free fatty acid concentrations were absent in HV rats, whether MA was administered alone or with 2-DG. The feeding response to glucoprivic challenges is influenced by the relative availability of alternate energy sources. The lack of feeding response to 2-DG during PN-100 is mediated by vagal input of hepatic fatty acid oxidation status.
Anti-interleukin-1 beta reduces sleep and sleep rebound after sleep deprivation in rats
Authors: Opp M. R. , Krueger J. M.
Published: December 2017

Interleukin-1 (IL-1) is somnogenic and is hypothesized to be involved in physiological sleep regulation. Antibodies directed against rat IL-1 beta were used to further elucidate possible contributions of IL-1 to sleep regulation. Rabbit anti-rat IL-1 beta (anti-IL-1 beta) was injected intracerebroventricularly into normal rats 15 min before light onset. A 20-microgram dose of anti-IL-1 beta reduced non-rapid-eye-movement (NREM) sleep by 60 min during the subsequent 12-h slight period. There was no effect on rapid eye movement sleep after this dose of anti-IL-1 beta. The effects of anti-IL-1 beta on the enhancement of sleep after periods of sleep deprivation were also determined. When rats were deprived of sleep for 3-h beginning at light onset, the amount of time spent in NREM sleep increased for the remaining 9 h of the light period, regardless of whether control intracerebroventricular injections of pyrogen-free saline or rabbit immunoglobulin G were given during the deprivation period. However, when 20 micrograms anti-IL-1 beta were injected intracerebroventricularly during the sleep deprivation period, the expected NREM sleep rebound was completely blocked. Collectively, these data provide additional support for the hypothesis that IL-1 is involved in regulation of physiological sleep-wake activity.
Relationship of growth and blood pressure in inbred rats
Authors: Schork N. J. , Jokelainen P. , Grant E. J. , Schork M. A. , Weder A. B.
Published: December 2017

Blood pressure and body weight rise with age, and hypertension is hypothesized to result from an early disorder of growth. We used the statistical technique of spline fitting to examine patterns of growth and rising blood pressure in individual inbred rats of the Wistar-Kyoto, spontaneously hypertensive (SHR), and stroke-prone SHR strains. Our results indicate that growth is phasic and that a well-defined growth spurt peaks at approximately 50 days of age in each strain. In addition, the time of maximal weight gain corresponds to the onset of a blood pressure spurt. The timing of this blood pressure rise was similar in the three strains, but the maximal rate of blood pressure rise was significantly higher in the hypertensive strains. Our results suggest that growth and rising blood pressure are intimately linked. Blood pressure appears to rise in response to a growth spurt, suggesting that there are growth-related events that trigger the cardiovascular response.
Substrate and acute temperature effects on turtle heart and liver mitochondria
Authors: Almeida-Val V. M. , Buck L. T. , Hochachka P. W.
Published: December 2017

The oxidative properties of heart and liver mitochondria from the Western painted turtle (Chrysemys picta bellii) were characterized on the basis of substrate preferences and temperature sensitivity. Turtle heart and liver mitochondria oxidize most substrates at 2- and 10-fold less, respectively, than rates obtained from the corresponding rat mitochondria. Krebs cycle intermediates, ketone bodies, and glutamate were oxidized at similarly high rates by turtle heart mitochondria (70.0-121.2 nmol O.min-1.mg protein-1). Fatty acylcarnitines were oxidized at approximately one-half of the above rates, and rates of amino acid oxidation were either not detectable or very low. Heart mitochondria oxidize ketone bodies at rates as high as pyruvate plus malate. Liver mitochondria oxidized Krebs cycle intermediates, amino acids, and fatty acids at similarly low rates (3.0-8.0 nmol O.min-1.mg protein-1). Typically, succinate was oxidized at the highest rates, 20.6 +/- 4.0 and 121.2 +/- 1.2 nmol O.min-1.mg protein-1, for liver and heart, respectively. Values for the rate of change of oxidation with a 10 degrees C increase (Q10) from heart and liver mitochondria oxidizing glutamate were calculated over the range 25-5 degrees C in 5 degrees C intervals; over the range 10-5 degrees C, Q10 values were 3.2 and 19.8, respectively. Q10 values calculated over the higher temperature intervals were lower. It is suggested that the large difference in temperature sensitivity between mitochondria from these two tissues and the ability of the heart mitochondria to oxidize ketone bodies at high rates are adaptations to recover from the long anoxic overwintering bouts experienced by this species.
Angiotensin and ANP secretion during chronically controlled increments in atrial pressure
Authors: Lohmeier T. E. , Shin Y. , Reinhart G. A. , Hester R. L.
Published: December 2017

The primary objective of this study was to determine whether angiotensin II (ANG II) has direct effects on the atrium to chronically stimulate the secretion of atrial natriuretic peptide (ANP) by actions that are independent of its vasoconstrictor and fluid-retaining effects that increase ANP secretion indirectly by raising atrial pressure. In five dogs, right atrial pressure (RAP) was controlled at approximately 5.5 mmHg above control levels for 8 days by employing an externally adjustable occluder around the pulmonary artery and a servo-control system, and plasma levels of ANG II were fixed at either normal (days 1-3 and 7-8) or high (days 4-6) physiological concentrations by chronic infusion of captopril+ANG II. When plasma ANG II was maintained at normal levels during servo-control of RAP, plasma ANP concentration increased five- to sixfold and sodium balance was achieved at a reduced arterial pressure (-14 mmHg). In contrast, despite increased plasma levels of ANP, the high rate of ANG II infusion produced marked sodium retention during the initial 24 h; however, the antinatriuresis was not sustained because the servo-control system partially deflated the pulmonary artery occluder to prevent fluid-induced increments in RAP. Moreover, in the absence of a change in RAP, high plasma levels of ANG II did not influence plasma ANP concentration. These findings indicate that the plasma levels of ANP achieved in heart failure increase renal excretory capability and allow fluid balance to be achieved at a substantial fall in mean arterial pressure as long as there is minimal involvement of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)
Phosphate loading prevents the decrease in ATP and increase in food intake produced by 2,5-anhydro-D-mannitol
Authors: Rawson N. E. , Friedman M. I.
Published: December 2017

The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) triggers feeding in rats apparently by its action in the liver. In vivo phosphorylation of this analogue decreases hepatic inorganic phosphate and ATP by trapping of phosphate in the mono- and diphosphorylated forms of 2,5-AM. To determine whether hepatic phosphate depletion and decreased ATP are involved in the eating response to 2,5-AM, rats were treated with excess sodium phosphate before injection of 2,5-AM. Phosphate loading prevented both the increase in food intake and the decrease in liver ATP, without affecting the changes seen in plasma fuels produced by 2,5-AM treatment. Phosphate loading did not influence water intake or eating elicited by insulin or 2-deoxy-D-glucose, indicating that the effect on 2,5-AM-induced eating was behaviorally specific and not due to malaise. These data suggest that 2,5-AM elicits eating by trapping phosphate and reducing ATP in liver.
Temperature increase abolishes ability of turtle olfactory receptors to discriminate similar odorant
Authors: Hanada T. , Kashiwayanagi M. , Kurihara K.
Published: December 2017

We examined the effects of temperature changes on odor-discriminating ability of turtle olfactory receptors in vivo by applying the cross-adaptation method to the olfactory bulbar responses. The olfactory system discriminated well all eight pairs of odorants examined at 5 and 18 degrees C. The ability of the olfactory receptors to discriminate pairs of odorants having similar structures (e.g., trans-3-hexenol and cis-3-hexenol; d-carvone and l-carvone) was reversibly abolished by increasing the temperature up to 40 degrees C, whereas discrimination of odorants having quite different structures was much less affected. The membrane fluidity of cells isolated from turtle olfactory epithelia and liposomes made of lipids extracted from the epithelia changed in a similar temperature range as for the decrease of the odor-discriminating ability, suggesting that an increase in membrane fluidity is correlated with the abolishment of the odor-discriminating ability. The present results also suggest that in vivo desensitization (adaptation) occurs not at the cellular level but at the receptor level. This mechanism was supported by the data recorded from a single olfactory cilium, showing that a single cell has both receptors for l-carvone and d-carvone and that the response to d-carvone appeared after the response to l-carvone was adapted.
Olfactory bulbectomy counteracts inhibitory effect of food restriction on reproductive function
Authors: Pieper D. R. , Lobocki C. A. , Karo K. H.
Published: December 2017

Previous studies have shown that bilateral removal of the olfactory bulbs (BX) results in a large increase in gonadotropin secretion in golden hamsters. The principal question addressed by the present study was whether BX would offset the inhibitory effect of food restriction on reproductive function. BX or sham (SH) BX male golden hamsters were fed ad libitum or were restricted to only enough food to maintain them at 70% of the body weight of control groups fed ad libitum. The SH-70% group underwent marked testicular regression after approximately 6-8 wk, but the testes size of the BX-70% hamsters decreased only in proportion to the decrease in body weight. The BX food-restricted group had to be fed more food to maintain the same weight as the SH-70% hamsters, and the BX-70% group also had a higher core body temperature, lower percent body fat, and higher serum free thyroxine levels than SH food-restricted animals. In summary, removal of the olfactory bulbs appears to facilitate tonic gonadotropin secretion, such that food restriction is no longer capable of inducing testicular regression. In addition, the olfactory bulbs may have a strong influence on metabolic function in golden hamsters.
Validation of deconvolution analysis of LH secretion and half-life
Authors: Mulligan T. , Delemarre-van de Waal H. A. , Johnson M. L. , Veldhuis J. D.
Published: December 2017

Deconvolution methods constitute a class of analytic tools to quantitate hormone secretion and/or clearance in vivo. Although mathematically rigorous, deconvolution techniques have assumed, rather than proven, validity. Accordingly, we tested the validity of deconvolution analysis on true-positive human, animal (sheep and monkey), and computer-simulated data using the luteinizing hormone (LH) pulse signal as a relevant paradigm. We found that multiparameter deconvolution analysis has high discriminative sensitivity (human data 91%, animal 81%, computer-stimulated 95%) and specificity (human 90%, animal 81%, computer-simulated 100%). Sensitivity was impaired by low secretory burst amplitude (< 0.1 IU.l-1.min-1), short interpulse interval (< 60 min), infrequent venous sampling (every 20-30 min), and high random experimental variation (e.g., noise > 15%). Specificity was hindered by noise. Deconvolution accurately characterized the unknown hormone half-life (r = +0.994) and production rate (r = +0.990). Interoperator reliability was high when statistically based criteria for secretory pulse detection were applied. We conclude that multiparameter deconvolution, within recognizable constraints, is a valid and reliable tool for in vivo investigation of hormone secretion and half-life.
cGMP and Ca2+ regulation of ion transport across the isolated porcine distal colon epithelium
Authors: DuVall M. D. , O'Grady S. M.
Published: December 2017

Intact epithelium from the porcine distal colon was stripped of serosal muscle and mounted in Ussing chambers to investigate the regulation of Na, Cl, and K transport by guanosine 3',5'-cyclic monophosphate (cGMP) and elevations in intracellular [Ca2+]. Under voltage-clamped conditions cGMP (250 microM) produced an increase in tissue short-circuit current (Isc) that reached a maximal value within 10-20 min and remained elevated > 40 min. This response was associated with an inhibition of NaCl absorption and stimulation of Cl and K secretion. In the absence of Cl the Isc also slowly increased but returned to baseline values within 20 min. Bicarbonate removal from both serosal and mucosal solutions or serosal bumetanide (20 microM) reduced the effect of cGMP on Isc by approximately 40%. When performed simultaneously, these conditions reduced the cGMP response by approximately 60%. Transepithelial Na and Cl flux measurements indicated that serosal bumetanide blocked increased Cl secretion without effecting changes in NaCl absorption. In contrast, mucosal amiloride blocked the effects of cGMP on NaCl absorption but not Cl secretion. The cGMP Isc response was potentiated in the presence of 1 mM, but not 10 microM, amiloride. Moreover, 1 mM amiloride inhibited Isc under control conditions but was ineffective in the presence of cGMP. The Ca2+ ionophore ionomycin (3 microM) produced a transient increase in the Isc that was also associated with a decrease in transepithelial NaCl absorption and an increase in Cl and K secretion. In contrast to cGMP, the ionomycin Isc response was eliminated after Cl removal from the bath.(ABSTRACT TRUNCATED AT 250 WORDS)
Interactions between effects of W-7, insulin, and hypoxia on glucose transport in skeletal muscle
Authors: Youn J. H. , Gulve E. A. , Henriksen E. J. , Holloszy J. O.
Published: December 2017

The calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) stimulates glucose transport in skeletal muscle, apparently by raising cytosolic Ca2+ (P. Palade. J. Biol. Chem. 262: 6142-6148, 1987; J.H. Youn, E.A. Gulve, and J.O. Holloszy. Am. J. Physiol. 260 (Cell Physiol. 29): C555-C561, 1991). This study was performed to describe the interactions between the effects of W-7 and those of hypoxia and of insulin on glucose transport. The effect on 3-O-methylglucose (3-MG) transport of 50 microM W-7 was additive to the effect of a maximal insulin stimulus (2,000 microU/ml) but not to the effect of maximal (60 min) hypoxic stimulus, suggesting that W-7 stimulates glucose transport via the same pathway as hypoxia, independent of the pathway activated by insulin. The effect of 50 microM W-7 was additive to that of a submaximal (20 min) hypoxia stimulus, indicating that W-7 does not interfere with the stimulation of glucose transport by hypoxia. In contrast, 50 microM W-7 had an inhibitory effect on stimulation of 3-MG transport by submaximally effective insulin levels, causing a fivefold increase in the concentration of insulin needed to produce a half-maximal stimulation of 3-MG transport, from approximately 70 to approximately 350 microU/ml (P < 0.05). Thus these data demonstrate that W-7 selectively inhibits insulin stimulation of glucose transport.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamics and baroreflex function in rats with nephrotic syndrome
Authors: Hinojosa-Laborde C. , Jones S. Y. , DiBona G. F.
Published: December 2017

The excess renal sodium retention leading to edema formation in the nephrotic syndrome (NS) is substantially dependent on increased efferent renal sympathetic nerve activity (RSNA). This study examined whether the hypoalbuminemia in NS is reflected as a decrease in cardiac output or cardiac function and whether the increased RSNA in NS is due to alterations in arterial and/or cardiopulmonary baroreflex function. NS was induced in rats with adriamycin (3.5 mg/kg i.v.), and they were studied 4 wk after injection. Mean arterial pressure (MAP) was similar in control (C) and NS rats. Cardiac indexes (CIs; cardiac output/body wt) were 29 +/- 1 and 26 +/- 1 ml.min-1.100 g-1 in C and NS rats, respectively. Total peripheral resistance indexes were significantly greater in NS than in C rats (4.7 +/- 0.2 vs. 4.1 +/- 0.1 mmHg.100 g.min.ml-1). Cardiac function during increases in cardiac filling pressure was not different between C and NS rats. The afferent limb of the arterial baroreflex was assessed by measuring aortic depressor nerve activity (ADNA) while the efferent limb was assessed by measuring RSNA in C and NS rats during increases in MAP. The central component of the arterial baroreflex was assessed from plots of RSNA (output) vs. ADNA (input). Comparisons between C and NS rats before and after vagotomy revealed no differences in the gains of any component of the arterial baroreflex. The cardiopulmonary baroreflex was assessed in a similar manner by measuring afferent vagus nerve activity (VGNA) and efferent RSNA during volume expansion before and after sinoaortic denervation (SAD). Before SAD, gains were similar in C and NS rats. After SAD, gains of the total (-1.59 +/- 0.44 vs. -3.64 +/- 0.65%/mmHg) and the central/efferent limb (-0.26 +/- 0.07 vs. -0.67 +/- 0.14 %/%) were significantly reduced (P < 0.05) in NS compared with C rats while the gain of the afferent limb of the reflex was similar in C and NS rats. These results indicate that NS rats with significant hypoalbuminemia maintain an arterial pressure similar to C rats by increasing total peripheral resistance, which serves to offset the tendency to a lower CI. Arterial baroreflex function in NS does not differ from that in C, but decreased cardiopulmonary baroreflex inhibition of RSNA in NS may contribute to the increased RSNA.
Alteration in IGF-I mRNA content of fetal swine tissues in response to maternal diabetes
Authors: Ramsay T. G. , Wolverton C. K. , Steele N. C.
Published: December 2017

Diabetes alters the level of insulin-like growth factor I (IGF-I) mRNA in tissues of postnatal animals, but the impact of maternal diabetes or gestational diabetes on IGF-I mRNA abundance in fetal tissues has not been examined. Pregnant pigs were injected with either buffer or alloxan (50 mg/kg) at day 75 of gestation to induce diabetes. Fetal tissue samples were collected at day 105 of gestation, and IGF-I mRNA abundance (densitometric units/10 micrograms total RNA) were estimated by specific ribonuclease protection assay. Fetal glucose and IGF-I concentrations were increased 166 and 34%, respectively, by maternal diabetes. Maternal diabetes induced an increase in abundance of IGF-I mRNA in fetal skeletal muscle, liver, heart, kidney, and placenta. IGF-I mRNA levels were depressed by maternal diabetes in fetal adipose tissue and brain compared with the respective tissues from fetuses of control pigs. These data indicate that circulating levels of IGF-I and the steady-state levels of IGF-I mRNA in fetal tissues can respond to the metabolic and endocrine alterations occurring during maternal diabetes. The large variation in expression and degree of response among fetal tissues indicates that the fetus experiences tissue-specific regulation of IGF-I expression during development.
Identification of gastrin as a growth peptide in human pancreatic cancer
Authors: Smith J. P. , Fantaskey A. P. , Liu G. , Zagon I. S.
Published: December 2017

The present study reports the first evidence that the gastrointestinal peptide gastrin stimulates the growth of several human pancreatic cancer cells in culture and in tumors transplanted to nude mice. Gastrin promoted growth of all cell lines tested at a dose comparable to the binding affinity, providing evidence for a physiologically relevant receptor. The stimulatory effects of gastrin were blocked by the CCK-B/gastrin receptor antagonist L-365,260 and not by the CCK-A receptor antagonist L-364,718. Growth of PANC-1 cells in culture were inhibited by L-365,260, suggesting that gastrin is tonically produced by PANC-1 cells for regulation of growth. Athymic nude mice bearing PANC-1 xenografts were treated for 24 days subcutaneously with either 1% bovine serum albumin (diluent), pentagastrin (1 mg/kg), or L-365,260 (1 mg/kg) twice daily. Tumors from the pentagastrin-treated mice were found to weigh more and have greater protein and DNA content than controls, whereas these values were all decreased in tumors of L-365,260-treated mice. Receptor binding capacity changed in tumors of animals treated with the peptide or antagonist, suggesting a regulatory process. Gastrin immunoreactivity was detected in a transplanted PANC-1 human tumor. These results identify gastrin as a potent trophic peptide that actively stimulates growth of human pancreatic cancer and does so through a CCK-B/gastrin-like receptor.
Aging alters the phase-resetting properties of a serotonin agonist on hamster circadian rhythmicity
Authors: Penev P. D. , Zee P. C. , Wallen E. P. , Turek F. W.
Published: December 2017

Serotonergic mechanisms are believed to play a considerable role in mediating the effects of photic and nonphotic stimuli on circadian rhythmicity. Because aging is associated with significant changes in the responsiveness of the rodent circadian system to major synchronizing agents in the environment, this study examined the phase-shifting effects of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin [8-OH-DPAT; 2.0, 5.0, and 8.0 mg/kg ip at circadian time 8 (CT 8)], on the 24-h activity rhythm of young (3-4 mo old) and old (18-19 mo old) golden hamsters. Aging was associated with a dramatic attenuation of the phase-shifting effects of 8-OH-DPAT in this species. The results suggest the existence of age-related deficits in the serotonergic control of mammalian circadian rhythmicity, which could interfere with the temporal adaptation of the senescent organism to its environment.
Intrapericardial denervation: responses to water immersion in rhesus monkeys
Authors: McKeever K. H. , Keil L. C. , Sandler H.
Published: December 2017

Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and endocrine alterations associated with 120 min of head-out water immersion. Five animals underwent complete intrapericardial denervation using the Randall technique, while the remaining six monkeys served as intact controls. Each animal was chronically instrumented with an electromagnetic flow probe on the ascending aorta, a strain gauge pressure transducer implanted in the apex of the left ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV. During immersion, LV end-diastolic pressure, urine flow, glomerular filtration rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each increased (P < 0.05) for intact and denervated monkeys. There were no alterations in free water clearance in either group during immersion, yet fractional excretion of free water increased (P < 0.05) in the intact monkeys. Plasma renin activity (PRA) decreased (P < 0.05) during immersion in intact monkeys but not the denervated animals. Plasma vasopressin (PVP) concentration decreased (P < 0.05) during the first 30 min of immersion in both groups but was not distinguishable from control by 60 min of immersion in denervated monkeys. These data demonstrate that complete cardiac denervation does not block the rise in plasma ANP or prevent the natriuresis associated with head-out water immersion. The suppression of PVP during the first minutes of immersion after complete cardiac denervation suggests that extracardiac sensing mechanisms associated with the induced fluid shifts may be responsible for the findings.
Effects of elevated fetal cortisol concentrations on the volume, secretion, and reabsorption of lung liquid
Authors: Wallace M. J. , Hooper S. B. , Harding R.
Published: December 2017

We have examined the role of cortisol in the gestational age-related increase in the ability of epinephrine to inhibit the secretion and induce the reabsorption of fetal lung liquid. Chronically catheterized fetal sheep were infused with either saline (n = 6) or increasing doses of cortisol (1.5-3.5 mg/day; n = 6) between 120 and 130 days of gestation (term approximately 145 days). Lung liquid volumes and secretion rates were measured at 120 days (before infusion) and at 125 days, and then at 130 days we tested the ability of epinephrine to inhibit lung liquid secretion and induce liquid reabsorption. Cortisol infusions increased fetal plasma cortisol and 3,5,3'-triiodothyronine (T3) concentrations to levels observed just before labor and significantly increased the age-related increase in fetal lung liquid volume and secretion rate. At 130 days, epinephrine caused a significantly greater rate of lung liquid reabsorption in cortisol-infused fetuses (10.3 +/- 2.3 ml/h) than in saline-infused fetuses (1.5 +/- 1.6 ml/h). We conclude that a premature elevation in circulating fetal cortisol concentrations, probably in conjunction with elevated T3 concentrations, prematurely increases the epinephrine-induced reabsorption of fetal lung liquid. It is likely, therefore, that the preparturient increase of fetal cortisol concentrations plays an important role in the clearance of lung liquid at birth.
Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding proteins by tumor necrosis factor
Authors: Fan J. , Char D. , Bagby G. J. , Gelato M. C. , Lang C. H.
Published: December 2017

The purpose of the present study was to determine 1) whether exogenous administration of tumor necrosis factor-alpha (TNF-alpha) alters insulin-like growth factor-I (IGF-I) and IGF-binding proteins (BPs) and 2) whether the enhanced endogenous production of TNF mediates the lipopolysaccharide (LPS)-induced changes in the IGF system. The overnight infusion of murine TNF-alpha reduced circulating concentrations of both growth hormone (GH) and IGF-I in fasted rats. Furthermore, TNF-alpha decreased IGF-I content in liver, gastrocnemius muscle, and pituitary. In contrast, TNF-alpha increased IGF-I content in kidney and brain. IGFBP-1 was increased in plasma, liver, and muscle in response to TNF-alpha. In a second study, rats were injected with LPS after treatment with a neutralizing anti-TNF antibody (Ab), and blood and tissues were collected 4 h later. In LPS-treated rats, plasma concentrations of GH and IGF-I were reduced. LPS also decreased the IGF-I content in liver and skeletal muscle and increased plasma, liver, and muscle concentrations of IGFBP-1. Pretreatment with anti-TNF Ab attenuated the LPS-induced reduction in IGF-I and the increased IGFBP-1 in plasma and liver and completely prevented the decrease in IGF-I observed in muscle. In contrast, the LPS-induced decrease in plasma GH and the increased IGFBP-1 observed in muscle were unaltered by the anti-TNF Ab.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of swimming and environmental hypoxia on coronary blood flow in rainbow trout
Authors: Gamperl A. K. , Axelsson M. , Farrell A. P.
Published: December 2017

Previous studies have suggested that trout cardiac performance is highly dependent on coronary blood flow during periods of increased activity or hypoxia. To examine the relationship between coronary perfusion and cardiac performance in swimming trout, cardiac output (Q), coronary blood flow (qcor), and dorsal aortic blood pressure were measured in rainbow trout (Oncorhynchus mykiss) during normoxia and hypoxia (PO2 approximately 9 kPa). In normoxic trout, stepwise changes in cardiovascular variables were observed as the swimming speed was incrementally increased from 0.15 body lengths (bl)/s to 1.0 bl/s. At 1.0 bl/s, qcor and cardiac power output had both increased by approximately 110%, and coronary artery resistance (Rcor) had decreased by 40%. During hypoxia, resting qcor was 35% higher, and Rcor was 20% lower, compared with normoxic values. In hypoxic swimming trout, the maximum changes in qcor (155% increase) and Rcor (50% decrease) were recorded at 0.75 bl/s. In contrast, cardiac power output and Q increased by an additional 40 and 20%, respectively, as swimming speed was increased from 0.75 to 1.0 bl/s. The results indicate that 1) increases in qcor parallel changes in cardiac power output; 2) during hypoxia there are compensatory increases in cardiac performance and coronary perfusion; and 3) the scope for increasing qcor in swimming trout is approximately 150%. In addition, results from preliminary experiments suggest that beta-adrenergic, but not cholinergic, mechanisms are involved in the regulation of coronary blood flow during exercise.
Role of cholecystokinin in the anorexia produced by duodenal delivery of oleic acid in rats
Authors: Woltman T. , Castellanos D. , Reidelberger R.
Published: December 2017

To assess the importance of triglyceride digestion products in producing satiety, we determined the effects of duodenal infusions of triolein, oleic acid, and oleic acid plus monoolein on meal patterns in ad libitum-feeding rats. Oleic acid and oleic acid plus monoolein inhibited feeding similarly; triolein's effect was delayed and fourfold less potent. We then used the type A cholecystokinin (CCK-A)-receptor antagonist devazepide to assess the importance of CCK in mediating the anorexia produced by oleic acid. Oleic acid (at 320, 440, and 640 mumol/h) inhibited 3-h intake dose dependently by 32, 56, and 75%, respectively. Devazepide (1 or 2 mg/kg) blocked the responses to the 320 mumol/h dose, but had little if any effect on responses to the larger doses. Devazepide (1 mg/kg) did block anorexic responses to 3-h cholecystokinin octapeptide infusions (3 and 10 nmol.kg-1.h-1 iv) that inhibited 3-h intake by 25 and 65%, respectively. Our results suggest that the satiety response to triolein is produced by the products of triolein digestion and that CCK plays a significant, indispensable role in mediating the satiety response to duodenal delivery of small but not large loads of oleic acid.
Indomethacin blocks the febrile response induced by interleukin-8 in rabbits
Authors: Zampronio A. R. , Silva C. A. , Cunha F. Q. , Ferreira S. H. , Pela I. R. , Souza G. E.
Published: December 2017

Interleukin (IL)-8 induces fever in rats by a mechanism independent of the release of cyclooxygenase products. The purpose of this study was to investigate whether a similar mechanism is responsible for the pyrogenic effect of IL-8 in rabbits. Intravenous (0.31-5.0 ng/kg) or intracerebroventricular (15.6-250 pg) injections of IL-8 induced a dose-dependent increase in body temperature. The correlations between the doses of recombinant human IL-8 and the fever index were 0.98 and 0.99 for the intravenous and intracerebroventricular injections, respectively. The pyrogenic activity of IL-8 was not due to contamination with lipopolysaccharide (LPS), inasmuch as the Limulus amoebocyte lysate test showed < 10 pg endotoxin/micrograms IL-8, and boiled IL-8 lost its pyrogenic activity. Indomethacin (2 and 5 mg/kg i.p.) abolished the febrile response induced by the intravenous injection of LPS (5.0 ng/kg), IL-1 beta (5 ng/kg), and IL-8 (5 ng/kg). Indomethacin also abolished the fever induced by the intracerebroventricular injection of IL-8 (62.5 pg) but only partially reduced the response induced by the injection of IL-1 beta (25 pg icv). These results show that, different from rats, indomethacin blocks the febrile response induced by the central or peripheral administration of IL-8 in rabbits.