bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin-like growth factor I promotes growth selectively in fetal sheep in late gestation
Authors: Lok F. , Owens J. A. , Mundy L. , Robinson J. S. , Owens P. C.
Published: December 2017

Insulin-like growth factor I (IGF-I) is required for normal fetal growth and skeletal maturation in late gestation, because null mutations of the IGF-I gene in mice reduce fetal weight and retard ossification of bones. To determine if, conversely, increased abundance of IGF-I promotes fetal growth and skeletal maturation, fetal sheep were infused intravascularly with recombinant human IGF-I (n = 7) (26 +/- 3 micrograms. h-1.kg-1) from 120 to 130 days gestation and compared with controls (n = 15). IGF-I infusion increased plasma IGF-I concentrations by 140% (P = 0.002) and weights of fetal liver, lungs, heart, kidneys, spleen, pituitary, and adrenal glands by 16-50% (P < 0.05). Weights and/or lengths of the fetus, placenta, gastrointestinal tract, individual skeletal muscles, and long bones were unchanged by IGF-I. However, IGF-I increased the percentage of proximal epiphyses of long bones present (P < 0.05) and their cross-sectional areas by 15 to 38% (P < 0.05). These results show that IGF-I promotes growth of major fetal organs, endocrine glands, and skeletal maturation in vivo, consistent with IGF-I actively controlling and not merely facilitating fetal growth. The variable response of different tissues may partly reflect tissue specificity in growth requirements for additional factors.
Electrogenic, proton-coupled, intestinal dipeptide transport in herbivorous and carnivorous teleosts
Authors: Thamotharan M. , Gomme J. , Zonno V. , Maffia M. , Storelli C. , Ahearn G. A.
Published: December 2017

In both herbivorous tilapia (Oreochromis mossambicus) and carnivorous rockfish (Sebastes caurinus) intestinal and pyloric cecal brush-border membrane vesicles (BBMV), [14C]glycylsarcosine ([14C]Gly-Sar) uptake was stimulated by a transmembrane proton gradient. A transmembrane K(+)-diffusion potential (inside negative) stimulated [14C]Gly-Sar uptake above that observed with short-circuited vesicles, whereas an inwardly directed Na+ gradient in both fishes had no effect on peptide uptake. In tilapia, [14C]Gly-Sar influx occurred by the combination of 1) a high-affinity, saturable, proton gradient-dependent carrier system [Kt [concentration that equals one-half of maximum influx (Jmax)] = 0.56 +/- 0.08 mM; Jmax = 1,945.0 +/- 174.6 pmol.mg protein-1.10 s-1]; 2) a low-affinity, nonsaturable (within 1-10 mM), proton gradient-dependent carrier system (nonsaturable carrier-mediated transport component = 4,514.0 +/- 28.1 pmol.mg protein-1.10 s-1.mM-1); and 3) a diffusional component accounting for < 10% of total influx within the concentration range tested. Influx (10 s) of 1-10 mM [14C]Gly-Sar in tilapia intestine was significantly (P < 0.01) inhibited by 10 mM diethylpyrocarbonate, a specific inhibitor of proton-coupled peptide transport systems. [14C]Gly-Sar influx into tilapia BBMV showed cis-inhibition and trans-stimulation by Gly-Pro, suggesting that [14C]Gly-Sar and Gly-Pro shared the same mucosal peptide transporter in fish. These observations strongly suggest that intestinal transport of peptides in herbivorous and carnivorous fishes is proton gradient dependent, electrogenic, sodium independent, and qualitatively resembles the peptide transport paradigm proposed for mammals.
Role of angiotensin II and catecholamines in blood pressure variability responses to stress in SHR
Authors: Gaudet E. , Blanc J. , Elghozi J. L.
Published: December 2017

The contribution of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) to blood pressure (BP) and heart rate (HR) variability responses to air-jet stress was assessed in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Activity of the encogenous RAS was suppressed by chronic treatment by a nonpeptide angiotensin II receptor antagonist (Iosartan). The role of alpha 1-adrenoceptor activity was evaluated in rats by acute administration of prazosin. In untreated animals, an air jet induced an increase in systolic BP (SBP; 9 +/- 2 mmHg for WKY and 8 +/- 2 mmHg for SHR) and in HR (56 +/- 19 beats/min for WKY and 76 +/- 8 beats/min for SHR), followed by an increase of the midfrequency (MF; 0.2-0.6 Hz) component of HR in WKY (183%) and by an increase of the MF component of SBP and diastolic BP in SHR (65%). Prazosin prevented BP rises as well as the MF component of BP and HR increases associated with air-jet stress. Chronic suppression of the RAS by losartan did not alter the BP response to the air jet in WKY and slightly reduced it in SHR but abolished all the BP and HR variability changes in both strains. These results indicate that the SNS but not RAS is essential for the BP rise induced by stress and demonstrate that RAS in conjunction with SNS is involved in BP and HR variability changes associated with stress.
Fatty acids enhance neurovascular reflex responses by effects on alpha 1-adrenoceptors
Authors: Stepniakowski K. T. , Sallee F. R. , Goodfriend T. L. , Zhang Z. , Egan B. M.
Published: December 2017

Abnormalities in plasma nonesterified fatty acids (NEFAs) may contribute to increased vascular alpha-adrenergic tone in obese hypertensive patients, because raising NEFAs locally enhances vascular reactivity to exogenously infused phenylephrine. However, responses to exogenous phenylephrine, a relatively selective alpha 1-adrenoceptor agonist, may not reflect the physiologically more important response to endogenous norepinephrine, a nonselective alpha-adrenoceptor agonist. To study the effects of NEFAs on vascular responses to endogenously released norepinephrine, dorsal hand venoconstrictor responses to thigh cuff inflation were quantified in nine healthy volunteers during coinfusion of Intralipid with heparin to raise fatty acids locally. Intralipid-heparin, which approximately doubled local linoleic and oleic acid concentrations (P < 0.05), increased the magnitude and duration of the venoconstrictor response to thigh cuff inflation (P < 0.005) and also enhanced venoconstrictor responses to locally infused phenylephrine but not clonidine, a relatively selective partial alpha 2-adrenoceptor agonist. The results of this study indicate that NEFAs enhance reflex vasoconstrictor responses largely through local effects on the vascular alpha 1-adrenoceptor and raise the possibility that fatty acids contribute to increased neurovascular tone in obese hypertensive patients.
Hindbrain GRP receptor blockade antagonizes feeding suppression by peripherally administered GRP
Authors: Ladenheim E. E. , Taylor J. E. , Coy D. H. , Moore K. A. , Moran T. H.
Published: December 2017

Bombesin (BN)-like peptides injected peripherally or centrally suppress food intake in rats. The relationship between the central and peripheral actions of BN is unknown. However, experimental evidence supports a critical role for the caudal hindbrain in mediating the feeding effects of BN. To investigate this relationship further, we examined the ability of fourth ventricular infusion of a specific gastrin-releasing peptide (GRP) antagonist, [D-F5, Phe6, D-Ala11]BN-(6-13) methyl ester (BN-ME), to block suppression of glucose intake (0.5 kcal/ml) produced by intraperitoneal administration of GRP-(18-27) in 5-h food-deprived male Sprague-Dawley rats (n = 10). We found that fourth ventricular administration of 10, 32, and 100 ng BN-ME blocked the suppression of glucose intake produced by peripherally administered 10 nmol/kg GRP-(18-27). The most effective dose of BN-ME (100 ng) blocked the ability of peripheral injection of GRP-(18-27) to inhibit glucose intake but had no effect on intake when given alone. These results demonstrate that the availability of caudal hindbrain GRP receptors is necessary for peripherally administered GRP-(18-27) to reduce food intake in rats.
First and second phases of biphasic fever: two sequential stages of the sickness syndrome?
Authors: Romanovsky A. A. , Kulchitsky V. A. , Akulich N. V. , Koulchitsky S. V. , Simons C. T. , Sessler D. I. , Gourine V. N.
Published: December 2017

We hypothesized that the systemic inflammatory response undergoes two consecutive stages, each characterized by different nonspecific sickness patterns. To test this hypothesis, we studied thermal, nociceptive, and motor responses to lipopolysaccharide (LPS) in 43 unanesthetized, habituated, and lightly restrained male Wistar rats previously implanted with a catheter in the jugular vein. Escherichia coli LPS was injected intravenously in a dose of 0, 0.1, 1, 10, 100, or 1,000 micrograms/kg. Colonic temperature (Tc) was measured with a thermocouple. Changes in nociception were assessed by tail flick latency (TFL) to a noxious heat stimulus. Motor activity was evaluated using an observation-based activity score (AS). The two lowest doses were apyrogenic. The next dose induced a monophasic fever with a maximal Tc rise of 0.9 +/- 0.2 degrees C at 108 +/- 11 min post-LPS. The next two higher doses caused biphasic fevers with the first and second peaks of 0.7 +/- 0.1 and 1.4 +/- 0.1 degrees C (10 micrograms/kg) and 0.7 +/- 0.1 and 1.4 +/- 0.2 degrees C (100 micrograms/kg) occurring at 60 +/- 6 and 165 +/- 17 min and at 45 +/- 3 and 141 +/- 6 min, respectively. The highest dose of LPS resulted in a Tc fall (nadir, -0.6 +/- 0.1 degree C at 83 +/- 6 min). Two different sickness patterns were exhibited. The first (high Tc, low TFL and high AS) occurred during the monophasic fever and the first (early) phase of the biphasic fevers, and it was termed the early phase syndrome. The second pattern (high or low Tc, high TFL, and low AS) developed during the second (late) phase of the biphasic fevers and LPS-hypothermia (endotoxin shock), and it was termed the late phase syndrome. Occurring at different stages of the systemic inflammatory response and developing through different coping patterns [fight/flight (energy expenditure) vs. depression/withdrawal (energy conservation)], the two syndromes represent two different types of adaptation to infection and have different biological significance. Viewing sickness as a dynamic entity is justified clinically. Such a dynamic approach to the problem resolves several contradictions in the current concept of sickness.
Evidence for the existence of endothelin-B receptor subtypes and their physiological roles in the rat
Authors: Gellai M. , Fletcher T. , Pullen M. , Nambi P.
Published: December 2017

The physiological roles of endothelin-B (ETB) receptor subtypes in systemic and renal hemodynamics were assessed in conscious Sprague-Dawley rats. Mean arterial pressure, hindlimb flow, and renal blood flow were measured via an implanted catheter and pulsed Doppler flow probes. Bolus intravenous injections of sarafotoxin 6c (S6c), a selective ETB agonist, elicited transient dose-dependent vasodilation, followed by sustained vasoconstriction in the systemic bed, but only vasoconstriction in the renal bed. RES-701-1, a selective ETB antagonist, blocked the dilator and potentiated the constrictor effect; SB-209670, a mixed ET receptor antagonist, attenuated both responses to S6c. In follow-up studies, the role of endogenous ET was assessed by administration of the antagonists alone: RES-701-1, SB-209670, and the ETA-selective antagonist BQ-123. RES-701-1 unmasked a significant systemic and renal vasoconstriction, which was attenuated by SB-209670 but not by BQ-123. SB-209670 and BQ-123 had no effect on basal hemodynamic parameters. Data from radioligand binding experiments showed that RES-701-1 binds with high affinity to the cloned human ETB receptor but poorly to the ETB receptor predominant in the rat kidney. Collectively, the results indicate that 1) the vascular effects of ET in the rat are mediated by two ETB receptor subtypes: an RES-701-1-sensitive subtype, mediating vasodilation, and an RES-701-1-insensitive subtype, mediating vasoconstriction; 2) the predominant role of endogenous ET is vasodilation; and 3) the ETA receptor plays a negligible role in the control of vascular tone in the rat.
Role of the renin-angiotensin system in mediating the effects of posture on renal function
Authors: Reinhart G. A. , Lohmeier T. E.
Published: December 2017

This study was designed to quantitate the influence of the neurohumoral activation associated with orthostatic stress on renal hemodynamics and sodium excretion and, furthermore, to determine the importance of the renin-angiotensin system in mediating these changes in renal function. Seven conscious dogs were studied while lying in the recumbent position and, subsequently, after standing in a supporting sling. Experiments were conducted under control conditions and after plasma angiotensin II (ANG II) concentration was fixed at control levels by chronic infusion of captopril (14 micrograms.kg-1.min-1) and ANG II (0.5 +/- 0.02 ng.kg-1.min-1). During control experiments, 45 min of standing increased plasma renin activity twofold, whereas mean arterial pressure, heart rate, and plasma norepinephrine concentration remained unchanged. During standing, glomerular filtration rate (GFR) and renal plasma flow (RPF) fell to 88 +/- 2 and 77 +/- 3% of recumbent values, respectively, whereas filtration fraction (FF) increased 16 +/- 1%. Additionally, urinary (UNaV) and fractional sodium excretion (FENa) decreased to 27 +/- 6 and 30 +/- 7% of recumbent values, respectively. When plasma ANG II concentration was fixed at control levels during standing, there were no significant changes in GFR, whereas increments in FF and reductions in RPF, UNaV, and FENa were attenuated by 63, 40, 30, and 33%, respectively. These data suggest that, in conscious dogs, standing in a supporting sling causes reflex activation of the sympathetic nervous and renin-angiotensin systems, eliciting reductions in GFR, RPF, and UNaV. Furthermore, ANG II contributes significantly to the effects of passive standing on renal hemodynamics and UNaV.
Effects of the lipase inhibitor orlistat on intake and preference for dietary fat in rats
Authors: Ackroff K. , Sclafani A.
Published: December 2017

Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to adult female rats. The rats responded to the drug-induced reduction in fat absorption by decreasing their dietary fat intake and increasing their protein and carbohydrate intake in a dose-related manner. Total caloric intake also increased, but body weight gain was inhibited compared with the nondrug control group. When Ols was removed from the diet, nutrient selection, caloric intake, and body weight returned to control levels. In additional short-term experiments (30 min/day), rats developed a preference for a plain fat diet over an Ols-fat diet (4 mg/g fat) and also for a cue flavor paired with plain fat over a flavor paired with Ols-fat. Yet, when not given the choice, the rats consumed nearly as much Ols-fat as plain fat diet. These results indicate that, by reducing fat absorption, Ols reduced the attractiveness of dietary fat, although it did not make the fat diet aversive. In clinical use, lipase inhibitors may be effective in reducing dietary fat intake by reducing both the consumption and absorption of fat.
Respiration and medullary blood flow during sinusoidal hypoxia in the peripherally chemodenervated cat
Authors: Yu Q. P. , Melton J. E. , Neubauer J. A. , Edelman N. H.
Published: December 2017

The hypothesis that hypoxic respiratory depression is mediated by changes in medullary blood flow (MBF) was assessed in 18 anesthetized, paralyzed, vagotomized, peripherally chemodenervated, ventilated cats exposed to sinusoidal hypoxic hypoxia. In nine cats, the dynamic response of the central respiratory controller to hypoxia was studied by varying the cycle time of sinusoidal hypoxia (cycle time = 2.5, 4, 6, 10, and 15 min). Peak phrenic neurogram amplitude (PNA) followed sinusoidal oscillations in the hypoxic input [arterial O2 saturation (SaO2)] at all cycle times. The relationship between PNA and SaO2 was expressed as the transfer function of the system and was approximated as a first-order differential equation with a time constant of 78 +/- 1 s, a value consistent with a previous measurement of the time constant of the change in respiration following a change in brain blood flow. In a separate study, MBF was continuously measured during sinusoidal hypoxia (cycle time = 6 min; n = 9) with a laser-Doppler flow probe to directly assess the role of MBF in production of hypoxic respiratory depression. PNA and MBF followed SaO2 oscillations during sinusoidal hypoxia. Infusion of sodium nitroprusside (20 micrograms.kg-1.min-1 iv) increased MBF by 30-40% and abolished MBF oscillations during subsequent sinusoidal hypoxia but had no effect on PNA oscillations. We conclude that the increase in brain blood flow seen during sinusoidal hypoxia is not the primary cause of the accompanying central hypoxic respiratory depression.
Fos induction in rat brain neurons after stimulation of the hepatoportal Na-sensitive mechanism
Authors: Morita H. , Yamashita Y. , Nishida Y. , Tokuda M. , Hatase O. , Hosomi H.
Published: December 2017

Responses of hepatic afferent nerves to intraportal bolus injection of hypertonic solutions were examined in anesthetized rats. Hepatic afferent nerve activity increased in response to an intraportal injection of 0.75 M NaCl or NaHCO3 but did not respond to a similar injection of 1.5 M mannitol, 0.75 M LiCl, or 0.15 M NaCl, implying that nerves in the hepatoportal area are sensitive to increases in Na concentrations and that this leads to stimulation of hepatic afferent nerve activity. To study central activation in response to stimulation of the hepatic Na-sensitive mechanism, c-fos induction was monitored. After electrical stimulation of hepatic afferent nerves, neurons containing Fos-like immunoreactivity (Fos-li) were found in the area postrema, nucleus of the solitary tract, paraventricular hypothalamic nucleus, and supraoptic nucleus at 90 min after stimulation. Induction of Fos-li was also studied after simultaneous infusion of 0.45 M NaCl into the portal vein and distilled water into the inferior vena cava in conscious rats so as to keep the total amount of solution introduced into the systemic circulation isotonic, thus avoiding changes in mean arterial pressure, plasma osmolality, and plasma NaCl concentrations. Fos-li-containing neurons were found in the same regions in which they were found after electrical stimulation. However, few, if any, Fos-li-containing cells were found if the rats were hepatically denervated or if they received an intraportal infusion of hypertonic LiCl or mannitol. These data provide evidence for involvement of the brain stem and forebrain structures in NaCl regulatory functions induced by stimulation of the hepatoportal Na-sensitive mechanism. However, stimulation of the hepatoportal osmosensitive mechanism does not activate these central structures.
Nitric oxide synthase inhibition reverses arteriolar hyporesponsiveness to endothelin-1 in septic rats
Authors: Hollenberg S. M. , Piotrowski M. J. , Parrillo J. E.
Published: December 2017

Persistent vasodilation refractory to vasopressor agents is the hemodynamic abnormality characteristic of septic shock. Induction of nitric oxide synthase (NOS) by sepsis-induced cytokines has been hypothesized to play a pathogenetic role in this refractory vasodilation. To evaluate the mechanism of vasodilation in sepsis, we used in vivo videomicroscopy to measure responses of resistance arterioles (15-20 microm) to topical suffusion of the potent vasoconstrictor, endothelin-1 (ET-1), in rat cremaster muscle. Rats made septic by cecal ligation and puncture were compared with controls that underwent sham ligation. Responses to topically suffused ET-1 were assessed in septic and control rats before and after superfusion of the muscle with the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Sepsis produced a decrease in ET-1-induced vasoconstriction; the ET-1 concentration-response curve was shifted to the right in septic rats (P < 0.05). Contractions at ET-1 concentrations of 1, 10, and 100 nM were 20, 28, and 32%, respectively, of sham controls. Superfusion of the muscle with L-NMMA restored arteriolar responsiveness to ET-1 in the septic rats, significantly increasing arteriolar constriction at 1 and 10 nM. This effect was reversed with superfusion of excess L-arginine (1 mM). This study demonstrates that impaired vasoconstriction in response to ET-1 in resistance arterioles of septic rats in vivo is reversed by NOS inhibition. Taken together with previous studies showing sepsis-induced impairment of vasoconstriction with norepinephrine, a vasopressor with a mechanism of action different from ET-1, these findings suggest a generalized abnormality in the responsiveness of resistance arterioles in sepsis. Reversal of hyporesponsiveness to both of these vasopressor agents by NOS inhibition suggests an important role for nitric oxide as a mediator of refractory vasodilation in sepsis.
Regulation of prostanoid vasomotor effects and receptors in choroidal vessels of newborn pigs
Authors: Abran D. , Varma D. R. , Chemtob S.
Published: December 2017

This study was conducted to determine if high perinatal prostaglandin (PG) and thromboxane (TxA2) levels modified their choroidal vasomotor effects and receptor levels. Both nonperfused (eyecup preparations) and perfused choroidal vessels from saline- or ibuprofen-treated 1-day-old pigs and tissues from adult pigs were used; all prostanoids produced similar vasomotor effects on both preparations. Choroidal PGF2alpha, TxA2, PGI2, and PGD2 levels were higher in the newborn than in adult pigs; injections of ibuprofen (40 mg/kg every 4 h for 48 h) into newborn pigs significantly decreased choroidal levels of all these prostanoids. PGF2alpha and the TxA2 mimetic U-46619 caused less choroidal vasoconstriction and production of inositol 1,4,5-trisphosphate (IP3) in the newborn than in adult pigs. Ibuprofen treatment increased choroidal PGF2alpha vasoconstrictor effects, IP3 production, and receptors, but did not modify response to U-46619. Carbaprostacyclin (PGI2 analog) caused a greater choroidal vasodilatation and adenosine adenosine 3',5'-cyclic monophosphate (cAMP) production in the newborn than in adult pigs; these effects were not modified by ibuprofen. PGD2 did not increase cAMP but caused greater dilatation and nitrite [oxidation product of nitric oxide (NO)] production in the choroid of newborn than of adult pigs, which were decreased to adult levels by ibuprofen and the NO synthase inhibitor N(omega)-nitro-L-arginine. These data suggest that high perinatal PG levels downregulate PGF2alpha receptors and vascular effects but do not modify choroidal responses to TxA2 and PGI2; NO seems to contribute to the vasodilator effects of PGD2.
Intracerebroventricular losartan inhibits postprandial drinking in sheep
Authors: Mathai M. , Evered M. D. , McKinley M. J.
Published: December 2017

We investigated the contribution of brain angiotensinergic mechanisms to postprandial drinking in sheep. Sheep in fluid balance were given 0.8 kg chaff for 30 min, and water intake was measured for the next hour. Intracerebroventricular infusion of the AT1 type angiotensin II (ANG II) receptor blocker losartan (1 mg/h) reduced postprandial drinking by approximately 70% (n = 7, P < 0.01) but did not affect food intake. The same losartan dose given intravenously had little or no effect on prandial drinking. Feeding increased Na+ concentrations in plasma and cerebrospinal fluid (CSF; n = 5, P < 0.05). Intracerebroventricular losartan (1 mg/h) inhibited the drinking responses to intracarotid infusion of ANG II (0.8 microg/min for 30 min, n = 4, P < 0.01) and to intracerebroventricular infusion of 0.5 M NaCl (1 ml/h for 1 h, n = 5, P < 0.05) but had no effect on drinking responses to intravenous infusion of 4 M NaCl (1.3 ml/min for 30 min). These findings indicate that a brain ANG II-dependent mechanism is involved in postprandial drinking in sheep. They suggest also that the mechanism by which increasing CSF Na+ causes thirst involves brain ANG II and is different from the mechanism subserving the drinking response to changes in blood Na+.
Modulation of ovine fetal adrenocorticotropin secretion by androstenedione and 17beta-estradiol
Authors: Saoud C. J. , Wood C. E.
Published: December 2017

Parturition in sheep is initiated by increases in activity of the fetal hypothalamic-pituitary-adrenal axis. We have previously reported that cortisol negative feedback efficacy is decreased at the end of gestation. The present study was designed to test the hypothesis that increasing plasma estrogen and/or androgen concentrations in the fetus might increase plasma adrenocorticotropic hormone (ACTH) concentration, either by stimulating ACTH secretion or by altering the negative feedback effect of cortisol on ACTH. Fetal sheep were chronically catheterized and treated with no steroid (control), 17beta-estradiol, or androstenedione (each approximately 0.24 mg/day). After catheterization and implantation of steroid pellet, fetuses were subjected to two short (10 min) periods of sodium nitroprusside-induced hypotension with or without pretreatment with intravenous infusion of hydrocortisone sodium succinate (0.5 microg/min) to test fetal ACTH responsiveness to stress and cortisol negative feedback efficacy. Estradiol treatment significantly increased basal plasma ACTH and cortisol concentrations relative to control fetuses but did not interfere with the inhibition of ACTH secretion by cortisol. Fetal plasma ACTH responses to hypotension were significantly suppressed approximately 60% in both control and estradiol-treated groups. Androstenedione treatment significantly increased basal fetal plasma ACTH and decreased basal fetal plasma cortisol concentration. Androstenedione did not alter stimulated levels of fetal ACTH but did block the inhibition of stimulated ACTH by cortisol. We conclude that increased fetal cortisol and ACTH secretion at the end of gestation may be due to the combined effects of the gonadal steroids in that estradiol increases basal plasma ACTH secretion while androstenedione reduces cortisol negative feedback efficacy.
Symmetric pH dependence of buffering power in giant fused cells from frog kidney proximal tubule
Authors: Bouyer P. , Cougnon M. , Thomas S. R. , Hulin P. , Anagnostopoulos T. , Planelles G.
Published: December 2017

This study measures the intrinsic buffering power (beta(i)) of giant fused cells from the proximal kidney tubule of the frog (Rana ridibunda) as a function of intracellular pH (pHi). We monitored pHi and transmembrane potential difference during acid or alkaline cell loading, achieved by removal of NH4Cl-containing solutions or CO2-HCO3(-)-equilibrated solutions, respectively, in the absence of extracellular Na+. Data were well fit by the equation for a single, monoprotic buffer with a maximum beta(i) at a pHi of 7.39 +/- 0.06 and a total buffer concentration of 30.7 +/- 1.6 mM (means +/- SD). From pHi measurements obtained during CO2-HCO3- exposure, we also calculated the buffering power afforded by the CO2-HCO3- pair, and we show its increasing contribution to total buffering power at increasing PCO2 and pHi. To our knowledge, this is the first report of a cell type in which intrinsic cell buffers can be adequately approximated as a single monoprotic buffer with a negative logarithm of apparent dissociation constant in the normal physiological range and essentially symmetric dependence on pHi in both acid and alkaline ranges.
Reduced insulin suppression of glucose appearance is related to susceptibility to dietary obesity in rats
Authors: Pagliassotti M. J. , Horton T. J. , Gayles E. C. , Koppenhafer T. A. , Rosenzweig T. D. , Hill J. O.
Published: December 2017

To examine the relationship between insulin action and body weight regulation in male rats, the following studies were performed. In study 1, rats (n = 31) were fed a low-fat diet (LFD) for 4 wk, and then glucose kinetics were estimated under basal and hyperinsulinemic conditions using the glucose clamp. After clamps, these same rats were placed on a high-fat diet (HFD) for 5 wk. In study 2, rats (n = 30) were fed an LFD for 3 wk and then a high-sucrose diet for 1 wk to produce selective hepatic insulin resistance. Clamps were then performed, and after clamps, these same rats were placed on an HFD for 5 wk. In study 3, rats (n = 30) were fed an LFD for 1 wk and then a high-sucrose diet for 3 wk to produce widespread insulin resistance. Clamps were then performed, and after clamps, these same rats were placed on an HFD for 5 wk. The rate of glucose appearance (R(a)) during the hyperinsulinemic clamps was the only pre-HFD variable that correlated (r = 0.49, P < 0.01 in study 1; r = 0.51, P < 0.001 in study 2) with weight gain on the HFD. Clamp R(a) also correlated with energy intake on the HFD in study 1 (r = 0.64, P < 0.001) and study 2 (r = 0.59, P < 0.001). Clamp R(a) and energy intake on the HFD accounted for similar portions of the variance in body weight gain on the HFD. Weight gain and fat-pad mass were increased (P < 0.05) in study 2 compared with study 1. In study 3, pre-HFD glucose kinetics were not correlated with energy intake or weight gain on the HFD. Widespread insulin resistance did not significantly reduce the rate of weight gain on the HFD. Thus insulin action on R(a) can influence body weight gain on an HFD. The effects of R(a) on body weight gain appear to be mediated via effects on energy intake. Selective hepatic insulin resistance can increase body weight gain on an HFD, but widespread insulin resistance does not significantly reduce HFD-induced weight gain.
Preoptic recess alpha-adrenoceptors control cardiovascular responses to hyperosmolality
Authors: Bealer S. L.
Published: December 2017

The roles of alpha-adrenoceptors in the anteroventral third ventricle (AV3V) and diagonal band of Broca (DBB) in cardiovascular responses to peripheral hypertonicity were investigated in conscious rats. Normal artificial cerebrospinal fluid (aCSF) or aCSF containing phentolamine (alpha1- and alpha2-antagonist), yohimbine (alpha2-antagonist), or prazosin (alpha1-antagonist) was perfused through microdialysis probes in the DBB, AV3V, or lateral ventricle during a 30-min infusion of isotonic (0.17 M; 0.1 or 1.7 ml x kg(-1) x min(-1) i.v.) or hypertonic (2.5 M; 0.1 ml x kg(-1) x min(-1) i.v.) NaCl. Hypertonic infusion increased blood pressure [mean arterial blood pressure (MAP); 17 +/- 2 mmHg] and decreased heart rate (HR; 36 +/- 6 beats/min). Both responses were abolished by AV3V administration of phentolamine or yohimbine, whereas prazosin selectively prevented the bradycardia. Phentolamine in the DBB or lateral ventricle did not alter either response. Stimulation of AV3V alpha1-adrenoceptors (phenylephrine) decreased HR and MAP, whereas alpha2-adrenoceptor stimulation (clonidine) produced bradycardia but increased MAP. Data suggest that alpha-adrenoceptors in the AV3V, but not the DBB, regulate cardiovascular responses to hyperosmolality.
Coupled oscillators account for the slow rhythms in sympathetic nerve discharge and phrenic nerve activity
Authors: Zhong S. , Zhou S. Y. , Gebber G. L. , Barman S. M.
Published: December 2017

Phase-locked slow rhythms in sympathetic nerve discharge (SND) and phrenic nerve activity (PNA) are generally thought to arise from a common brain stem "cardiorespiratory" oscillator. The results obtained in vagotomized and baroreceptor-denervated cats anesthetized with pentobarbital sodium do not support this view. First, partial coherence analysis revealed that the discharges of pairs of sympathetic nerves remained correlated at the frequency of the central respiratory cycle after mathematical removal of the portion of these signals common to PNA. The residual coherence suggests that the slow rhythm in SND is dependent on central mechanisms in addition to those responsible for rhythmic PNA. Second, the rhythms in SND and PNA became coupled in a 2:1 relationship during either moderate systemic hypocapnia or hypercapnia. Third, the slow rhythm in SND was maintained when rhythmic PNA was eliminated during extreme hypocapnia. Fourth, during extreme hypercapnia, coherence of the rhythms in SND and PNA was drastically reduced. These results suggest that the slow rhythms in SND and PNA arise from separate oscillators that are normally coupled.
Effects of artificial calculosis on rat ureter motility: peripheral contribution to the pain of ureteric colic
Authors: Laird J. M. , Roza C. , Cervero F.
Published: December 2017

The contribution of changes in ureter motility produced by a stone to the pain of ureteric calculosis is unclear. In this study we measured ureter motility as changes in intraureter pressure in anesthetized rats 1, 4, and 8 d ys after implantation of an artificial calculus (n = 33) and compared it with motility in normal (n = 8) and ligated (n = 4) ureters. Partial obstruction of the ureter by the stone produced a 478% increase in the amplitude of contractions, a 70% decrease in the rate of contractions, and a 66% decrease in the baseline pressure. The pressures reached during contractions were equivalent to those evoking nociceptive reactions in animals and humans. These changes persisted in rats that had spontaneously eliminated the stone. Complete obstruction of the ureter by the stone or by ligation abolished contractions. We conclude that the increased motility caused by a stone likely contributes to the development and maintenance of visceral pain and referred hyperalgesia in ureteric colic and to the persistence of referred hyperalgesia after elimination of the stone.
Sarcolemmal Ca influx through L-type Ca channels in ventricular myocytes of a teleost fish
Authors: Vornanen M.
Published: December 2017

The whole cell patch clamp method was used to measure Ca current through L-type Ca channels in enzymatically isolated ventricular myocytes of crucian carp (Carassius carassius L.) heart. Fish were acclimated to 22 degrees C for more than 4 wk, and properties of Ca current were measured at room temperature (21 +/- 1 degrees C). Depolarizing voltage steps from -50 mV evoked rapidly activating Ca currents, which exhibited a bell-shaped voltage dependence with peak amplitude at 0 mV. The currents were suppressed by nifedipine (5 microM), verapamil (2.5 microM), and Cd2+ (175 microM). The current amplitude was increased by 67.5 +/- 17.2% (n = 5) in the presence of 1 microM isoproterenol. Steady-state inactivation and activation curves showed half-maximal inactivation at -31.3 +/- 0.95 mV, with a slope factor of 5.88 +/- 0.51, and half-maximal activation at -10.6 +/- 1.65 mV, with a slope factor of 7.84 +/- 0.54 (n = 9). The overlap of inactivation and activation curves suggests the presence of a small window current, which is maximally 4% of the peak current at -27 mV. The density of L-type Ca current was 6.95 +/- 0.79 pA/pF at 0 mV (n = 35). A total increment in cellular Ca contributed by L-type Ca current during a 500-ms voltage clamp pulse was calculated from the integral of Ca current and cell volume. The charge transfer through L-type Ca current was 0.325 +/- 0.023 pC/pF, and the mean cell volume was 1,377 +/- 44 microns3. The increment in total cellular Ca by Ca influx through L-type Ca channels was calculated to be 39.3 +/- 2.8 microM. These findings imply that Ca influx through L-type Ca channels can contribute significantly to the activation of contraction in the ventricular myocytes of fish heart.
Female rats do not develop sucrose-induced insulin resistance
Authors: Horton T. J. , Gayles E. C. , Prach P. A. , Koppenhafer T. A. , Pagliassotti M. J.
Published: December 2017

In male rats, 2 wk of high-sucrose feeding results in insulin resistance and hypertriglyceridemia [Pagliassotti, M.J., P.A. Prach, T.A. Koppenhafer, and D.A. Pan. Am. J. Physiol. 271 (Regulatory Integrative Comp. Physiol. 40): R1319-R1326, 1996]. The present study aimed to determine if female rats also become insulin resistant and hypertriglyceridemic in response to high-sucrose feeding. Female Wistar rats (7 wk old) were fed either a high-sucrose diet (68% energy) (SU) or a high-starch diet (68% energy) (ST) for 3, 5, or 8 wk. In each animal, glucose kinetics were measured using [3-(3)H]glucose under basal and hyperinsulinemic conditions (insulin infusion 4.0 mU.kg-1.min-1). Body weight and basal glucose kinetics were not different between diet groups at 3, 5, or 8 wk. Glucose infusion rate (mg.kg-1.min-1) was not different between groups (3 wk: 17.7 +/- 1.6 ST, 16.6 +/- 0.9 SU; 5 wk: 16.1 +/- 0.9 ST, 15.1 +/- 2.0 SU; 8 wk: 18.3 +/- 1.9 ST, 16.1 +/- 1.5 SU). Clamp rate of glucose appearance (mg.kg-1.min-1) was also not different between diet groups (3 wk: 4.0 +/- 1.6 ST, 3.6 +/- 1.4 SU; 5 wk: 2.6 +/- 1.0 ST, 2.3 +/- 1.14 SU; 8 wk: 5.9 +/- 1.8 ST, 7.7 +/- 1.2 SU). No difference was observed in plasma and tissue triglycerides or tissue glycogen between sucrose- and starch-fed animals. We therefore conclude that female rats, in contrast to males, do not develop sucrose-induced insulin resistance and hypertriglyceridemia.
Lymph flow in sheep with rapid cardiac ventricular pacing
Authors: Drake R. E. , Dhother S. , Teague R. A. , Gabel J. C.
Published: December 2017

Increases in systemic venous pressure (Pv) associated with heart failure cause an increase in microvascular fluid filtration into the tissue spaces. By removing this excess filtrate from the tissues, lymphatic vessels help to prevent edema. However, the lymphatics drain into systemic veins and an increase in Pv may interfere with lymphatic flow. To test this, we cannulated caudal mediastinal node efferent lymphatics in sheep. We used rapid cardiac ventricular pacing (240-275 beats/min) to cause heart failure for 4-7 days. Each day we determined the lymph flow rate two ways. First, we adjusted the lymph cannula height so that the pressure at the outflow end of the lymphatic was zero. After we determined the lymph flow with zero outflow pressure, we raised the cannula so that outflow pressure was equal to the actual venous pressure. We quantitated the effect of venous pressure on lymph flow rate by comparing the flow rate with outflow pressure = Pv to the flow rate with zero out low pressure. At baseline, Pv = 5.0 +/- 2.5 (SD) cmH2O and we found no difference in the two lymph flow rates. Pacing caused Pv and both lymph flow rates to increase significantly. However for Pv < 15 cmH2O, we found little difference in the two lymph flow rates. Thus increases in Pv to 15 cmH2O at the outflow to the lymphatics had little effect on lymph flow. By comparison, Pv > 15 cmH2O slowed lymph flow by 55 +/- 29% relative to the lymph flow rate with zero outflow pressure. Thus Pv values > 15 cmH2O interfere with lymph flow from the sheep caudal mediastinal lymph node.
Chemical lesion of visceral afferents causes transient overconsumption of unfamiliar high-fat diets in rats
Authors: Chavez M. , Kelly L. , York D. A. , Berthoud H. R.
Published: December 2017

Because it is commonly assumed that the major role of visceral afferents in food intake control is to terminate meals by carrying negative-feedback signals to the brain, we hypothesized that overconsumption should occur in rats with chemically lesioned visceral afferents if they were presented with an unfamiliar diet. Adult male Sprague-Dawley (SD) rats were treated with multiple doses of capsaicin or vehicle as a control. Five weeks later, a series of 3-h feeding tests after 24-h deprivation was carried out, first with chow and then with either a solid (vegetable shortening) or liquid (Ensure) unfamiliar high-fat diet. Both groups consumed similar amounts of their powdered chow maintenance diet, but capsaicin-treated rats consumed at least 50% more of either high-fat diet than vehicle controls (P < 0.01) at the beginning of the first trial. During second and third trials with the now-familiar high-fat diet, intake was no longer significantly different between the two groups, suggesting rapid engagement of redundant control mechanisms. These results support a role of capsaicin-sensitive visceral afferents in providing negative feedback for early meal termination during the ingestion of unfamiliar diets.
Afferent renal inputs onto subfornical organ neurons responsive to angiotensin II
Authors: Ciriello J.
Published: December 2017

Experiments were done in pentobarbital sodium-anesthetized rats to investigate the effect of electrical stimulation of afferent renal nerves (ARN) on the discharge rate of subfornical organ (SFO) neurons that responded to changes in plasma levels of angiotensin II (ANG II) and projected directly to the paraventricular nucleus of the hypothalamus (PVH). Extracellular recordings were made from 76 histologically verified single neurons in the SFO that were excited by intracarotid infusions of ANG II. Of these units, 54.8% (23 of 42) responded with excitation to ARN stimulation (mean onset latency, 125 +/- 35 ms). None of the SFO units excited by plasma ANG II were found to be inhibited by ARN stimulation. An additional 34 units in the SFO that were excited by plasma ANG II were also antidromically activated by stimulation of the PVH. Of these neurons, 17.8% (6 of 34) were also excited by stimulation of ARN. The results indicate that inputs from ARN converge onto SFO neurons that alter their discharge rate during changes in plasma concentration of ANG II and project directly to the PVH. These data suggest that ARN may play an important role in body fluid balance and circulatory regulation by modulating the activity of SFO neurons that function in the detection of blood-borne signals resulting from the decrease in extracellular fluid volume and arterial pressure and that influence the activity of hypothalamic nuclei that contain neurosecretory neurons.
Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain
Authors: Cao C. , Matsumura K. , Yamagata K. , Watanabe Y.
Published: December 2017

We previously showed that a febrile dose of lipopolysaccharide (LPS) in rats resulted in induction of cyclooxygenase-2 (COX-2) mRNA in brain blood vessels/leptomeninges and telencephalic neurons. To elucidate the causal link between fever and LPS-induced COX-2 mRNA, we experimentally modified one or the other of these parameters and examined their relation. 1) LPS-induced fever was suppressed by pretreatment with a COX-2-specific inhibitor. 2) Levels of COX-2 mRNA in the neurons and blood vessels 2.5 h after LPS administration were even higher in the inhibitor-pretreated rats (afebrile) than in vehicle-pretreated ones (febrile). 3) After repeated administration of LPS, rats became tolerant to LPS, in which state LPS induced neither fever nor COX-2 mRNA in blood vessels/leptomeninges. When rats had not completely established LPS tolerance, they showed various degrees of fever that were closely correlated with the level of COX-2 mRNA in blood vessels but not with that in neurons. 4) Urethan anesthesia reduced basal as well as LPS-induced COX-2 mRNA in telencephalic neurons, but the rats still responded to LPS with fever and induction of COX-2 mRNA in the blood vessels/leptomeninges. These results suggest that COX-2 induced in brain blood vessels/leptomeninges is involved in the molecular mechanism of LPS-induced fever.
Development of REM and slow wave sleep in the rat
Authors: Frank M. G. , Heller H. C.
Published: December 2017

Active sleep (AS) in the neonate has been considered to be an immature form of rapid eye movement (REM) sleep. Quiet sleep (QS) has been thought to represent an immature form of slow wave sleep (SWS). To determine the relationship between the behaviorally determined states of AS and QS and electrographically determined REM sleep and SWS, we examined sleep ontogeny in the developing rat using an experimental routine that permitted long-term recordings and minimized the effects of maternal separation. Under these conditions, a transient state that included electroencephalographic slow wave activity and phasic motor activity was eventually replaced with the mature SWS pattern. Our work suggests that neonatal QS is not an immature form of SWS and that AS is best considered as an undifferentiated behavioral state from which both SWS and REM sleep develop.
Effect of a cholecystokinin-A receptor blocker on protein-induced food intake suppression in rats
Authors: Trigazis L. , Orttmann A. , Anderson G. H.
Published: December 2017

To test the hypothesis that only dietary protein (Pro; chicken egg albumin) and not amino acids (AA), carbohydrates (CHO; cornstarch), or fats (Fat; corn oil) produces a satiating effect via cholecystokinin (CCK) receptors, devazepide was coadministered with each macronutrient. Given alone (in 4 ml ig), Pro (0.75, 1.0, and 1.5 g), AA (1.0 g), CHO (1.4 g), and Fat (2.4 g) suppressed (P < 0.05) food intake in the first hour by 0.5, 0.8, and 1.1 g; 1.9 g; and 1.0 g, respectively, and in the first 2 h of feeding by 0.8, 1.2, and 1.3 g; 1.7 g; 0.7 g; and 1.5 g, respectively. When coadministered with devazepide (0.5 mg/kg body wt ig), the suppression of food intake caused by Pro, AA, CHO, and Fat treatments was modulated in the first hour by 60, 50, and 55%; 16%, 11%; and 10%, respectively, and during 0-2 h by 63, 92, and 54%; 29%; 0%; and -20%, respectively. Devazepide (0.5 mg/kg) given intraperitoneally also modulated Pro intake suppression during the first hour by 33% and during 0-2 h by 79%. Devazepide appears to interact with mechanisms of Pro-induced food intake suppression, but not AA-, Fat-, or CHO-induced food intake suppression. These studies provide evidence that CCK receptors play a role in Pro (albumin)- but not AA-, CHO (corn starch)-, or Fat (corn oil)-induced food intake suppression in rats.
Splenectomy impairs lymphocytosis during maximal exercise
Authors: Nielsen H. B. , Secher N. H. , Kristensen J. H. , Christensen N. J. , Espersen K. , Pedersen B. K.
Published: December 2017

To evaluate the role of the spleen for the exercise-induced lymphocytosis, six splenectomized subjects and six matched control subjects cycled for 12 min at two submaximal work rates corresponding to 50 and 75% of their maximal work capacity, followed by a supramaximal intensity maintained until exhaustion (16 +/- 1 min; mean +/- SE). Venous blood samples were taken before, during, and 2 h after the maximal load. In both groups, the concentration of lymphocytes became elevated during exercise, but the increase from the level at rest was impaired in the splenectomized subjects compared with that of the controls (118 +/- 34 vs. 238 +/- 38%; P < 0.05). This was reflected in several lymphocyte subsets: cluster designation (CD) 3+ cells (pan T lymphocytes), 69 +/- 19 vs. 204 +/- 37%; CD8+ cells (T lymphocyte subset), 164 +/- 41 vs. 467 +/- 68%; CD16+ cells [natural killer (NK) cells], 291 +/- 88 vs. 870 +/- 177%; CD56+ cells (NK cells), 301 +/- 108 vs. 753 +/- 187%. Also, the specific NK cell lysis of target cells (NK cell activity) during exercise was lower for the splenectomized subjects (30 +/- 7%) than that of the control subjects (52 +/- 10%), but evaluation of lytic units indicates that this was due to a reduced number of NK cells in the assay rather than insufficient cell lysis. Plasma catecholamines reached the same level in the splenectomized subjects and control subjects, which was taken to reflect that the activity of the sympathetic nervous system was similar in the two groups of subjects. Thus the major finding of this study is that the spleen is important for lymphocytosis during exercise, accounting for two-thirds of the increase in T lymphocytes and NK cells.