bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional interactions between thermosensitive neurons in diencephalic slices
Authors: Dean J. B. , Kaple M. L. , Boulant J. A.
Published: December 2017

Rat brain slices were used to investigate regional interactions between thermosensitive neurons in different diencephalic regions. Horizontal tissue slices rested over three thermodes. This permitted independent thermal stimulation of rostral, middle, and caudal regions. Thermocouples measured tissue temperatures in these three locations, and extracellular recordings measured neuronal responses to temperature changes both locally (at the site of the recorded neuron) and in remote regions of the slice. Many of the neurons that were sensitive to remote temperatures were located near the lateral border of the diencephalic nuclei, especially in the perifornical area. All neurons displaying remote thermosensitivity also displayed local thermosensitivity. These neurons usually showed opposite responses to remote and local temperatures; i.e., most of these neurons were locally warm sensitive but showed cold sensitivity to remote temperatures. These findings indicate that thermosensitive synaptic networks extend throughout the diencephalon and may explain the effect of temperature on a variety of homeostatic systems.
Tumor necrosis factor-beta induces sleep, fever, and anorexia
Authors: Kapas L. , Krueger J. M.
Published: December 2017

The enhanced sleep, fever, and anorexia experienced during general infections are attributed to the increased production of cytokines. Cytokines such as interleukin-1 and tumor necrosis factor-alpha (TNF-alpha) have characteristic somnogenic, pyrogenic, and anorectic effects. TNF-beta is closely related to TNF-alpha, and they share common receptors. The effects of TNF-beta on sleep-wake activity, brain temperature (Tbr), and food intake were, however, heretofore unknown. We injected 0.5-200 ng TNF-beta into rabbits intracerebroventricularly (icv) in the light period, and the electroencephalogram, movement, and Tbr were recorded for 6 h from rabbits. The highest dose, 200 ng TNF-beta, induced increases in non-rapid-eye-movement sleep and decreases in rapid-eye-movement sleep accompanied with biphasic febrile responses. Icv injection of 100 ng TNF-beta at dark onset suppressed 12-h and 24-h food intake in rats. These data suggest to us that TNF-beta may belong to the group of endogenous pyrogens/sleep factors.
Metabolic state of the in situ perfused trout heart during severe hypoxia
Authors: Arthur P. G. , Keen J. E. , Hochachka P. W. , Farrell A. P.
Published: December 2017

An in situ perfused heart preparation was used to study the effects of severe hypoxia in the rainbow trout, Oncorhynchus mykiss. Hypoxic trout hearts were capable of generating similar power outputs and ATP turnovers to normoxic counterparts at subphysiological work regimes. However, lactate efflux was 35-fold higher and glycolytic rate was calculated to be > 10-fold higher in hypoxic than in normoxic hearts. The surprising ability of trout hearts to withstand severe hypoxia appears to be related to the rapid removal of lactate and associated protons from the heart. An increase in power demand to normal in vivo levels caused rapid failure in hypoxic hearts. Failure was caused by a decline in stroke volume (contractility) and was not a consequence of heart rate deterioration. Hypoxia caused marked declines in the concentration of creatine phosphate but not ATP, and we suggest that an increase in intracellular phosphate was the primary cause of failure.
Clonidine in the prepyriform cortex blocked anorectic response to amino acid imbalance
Authors: Gietzen D. W. , Beverly J. L.
Published: December 2017

Ingestion of imbalanced amino acid diets (IMB) has been associated with a decrease in norepinephrine (NE) concentration in the prepyriform cortex (PPC), an area essential for the anorectic response to IMB. Decreased NE could result from activity-induced release (and subsequent metabolism) of the transmitter. If activity of the NE system is important in the rat's anorectic response to IMB, reduced NE activity should result in increased IMB intake. Therefore, the feeding response to IMB was measured after injecting clonidine (Clon) into the PPC to inhibit NE release. At 3 and 6 h after Clon (1.0 and 1.5 micrograms/rat) injections, IMB intake was increased from 69 (the usual response to IMB in untreated animals) to > 100% of control intake. Effective injection sites did not include the gustatory neocortex, an area important for conditioned taste aversions. Thus activation of the NE system in the PPC may be associated with the initial reduced intake of IMB, suggesting that NE activity in the PPC has a role in the neural mechanisms that subserve recognition of amino acid deficiency.
Gestational changes in Ca2+ transport across rat placenta and mRNA for calbindin9K and Ca(2+)-ATPase
Authors: Glazier J. D. , Atkinson D. E. , Thornburg K. L. , Sharpe P. T. , Edwards D. , Boyd R. D. , Sibley C. P.
Published: December 2017

The unidirectional maternofetal clearance (Kmf) of 45Ca was measured across the rat placenta over the last one-third of gestation. Kmf for 45Ca normalized to its diffusion coefficient in water (Kmf/Dw) increased 72-fold between days 15 and 22 of gestation from 3.5 +/- 0.3 to 253.1 +/- 22.0 cm/g placenta, respectively. At 15 and 18 days of gestation, Kmf/Dw for 45Ca was similar to Kmf/Dw for the paracellular marker [14C]mannitol, but at 21 and 22 days of gestation, Kmf/Dw for 45Ca was significantly higher than Kmf/Dw for [14C]mannitol, indicating that an additional route of transfer, other than diffusion, becomes available to calcium during this period. Northern hybridization analysis demonstrated that rat placental calbindin9K-to-beta-actin mRNA ratio increased 135-fold between 15 and 22 days of gestation and was temporally associated with the gestational increase in Kmf/Dw for 45Ca. In contrast, rat placental Ca(2+)-ATPase-to-beta-actin mRNA ratio increased only two- to threefold over the same gestational period and did not mirror the gestational changes in calcium clearance. These trends suggest that the expression of placental calbindin9K, but not Ca(2+)-ATPase, may be rate limiting to placental calcium transport in the rat.
Adrenal corticosteroid secretion in fetal sheep: pulsatile pattern at rest
Authors: Jackson B. T. , Lee A. F. , Morrison S. H. , Baker R. M. , Cohn H. E. , Piasecki G. J.
Published: December 2017

This study was undertaken to define the resting pattern of fetal pituitary-adrenocortical function. Experiments were performed at 127-145 days gestation in fetal sheep with chronic peripheral and adrenal cannulas inserted under halothane anesthesia. With the fetus in a baseline state, over 6 h, at 30-min intervals, maternal and fetal peripheral samples were collected for blood gases and cortisol (F), corticosterone (B), and adrenocorticotropic hormone (ACTH) concentrations, and three successive, 2-min adrenal samples were collected for determination of F and B secretion rates. We observed high-frequency, episodic bursts of F secretion. A lower frequency oscillation of F secretion, with a period of approximately 90 min, was defined by cosinor analysis. The mean amplitude of the oscillation increased from 45 to 507 ng/min with advancing gestation. The pattern of B secretion was similar to that for F but was quantitatively lower. An oscillatory period of approximately 90 min for plasma F was present in a majority of experiments. Pulsatile rhythms for ACTH were defined in 10 of 14 experiments, with periods ranging from 1.64 h in the least mature group to 2.37 h in the oldest fetus. Mean data revealed exponential increases in both F secretion and plasma ACTH from 129 to 145 days gestation.
Characterization of norepinephrine-stimulated protein synthesis in rat brown adipocytes
Authors: Waldbillig D. , Desautels M.
Published: December 2017

Rat brown adipocytes were incubated for 24 h with or without norepinephrine (NE) in Dulbecco's modified Eagle's medium with albumin, calf serum, and antibiotics. Brown fat cells were viable as defined by unchanged cell morphology, ATP content, or basal and NE-stimulated respiration. However, a 24-h exposure to NE led to a decline in NE-stimulated respiration that was not due to loss of thermogenic capacity. Brown fat cells incubated with or without NE had similar protein, succinate dehydrogenase, and uncoupling protein (UCP) content. These results differ from those observed after food deprivation in rats where loss of mitochondrial proteins occurs within 24 h, suggesting that reduced exposure to NE is not the only factor responsible for brown fat atrophy. NE increased [35S]methionine incorporation into cellular proteins, mitochondrial proteins, and UCP. The effect of NE on cell protein synthesis was inhibited by propranolol but not by prazosin. It was also inhibited 95% by cycloheximide but only partially (50%) by actinomycin D in contrast to NE stimulation of UCP labeling, which required RNA transcription. Chloramphenicol-sensitive protein synthesis was stimulated by NE. These results indicate a trophic action of NE in brown adipocytes exerted both at the level of RNA transcription and translation.
Effects of estrogen on whole animal and tissue glucose use in female and male rainbow trout
Authors: Washburn B. S. , Bruss M. L. , Avery E. H. , Freedland R. A.
Published: December 2017

Reports of changes in carbohydrate metabolism during vitellogenesis in fish prompted an investigation of the effects of estrogen on glucose utilization in rainbow trout. Estrogen pellets were implanted in both female and male fish, and a third group of male fish was given a sham operation. After cannulation of the dorsal aorta, D-[1-3H]glucose and 2-deoxy-D-[U-14C]glucose were injected into the fish to observe whole animal and tissue glucose use. We found that estrogen does not affect glucose turnover rate or transit time but causes a decrease in plasma glucose concentration and size of the glucose mixing pool. Adipose tissue in female fish utilized glucose at a higher rate than sham fish. Ovarian tissue used more glucose per kilogram of body weight than the testes of the male fish. Regardless of treatment, brain had the highest rate of glucose consumption per gram of tissue, followed by gonads and red blood cells. Muscle and adipose tissue utilized only small amounts (< 1 nmol.g tissue-1.min-1) of glucose. We conclude that an increase in the rate of whole body glucose use is not responsible for the fall in plasma glucose caused by estrogen and seen during vitellogenesis.
AV3V lesion impairs responses induced by cholinergic activation of SFO in rats
Authors: Colombari D. S. , Saad W. A. , Camargo L. A. , Renzi A. , de Luca Junior L. A. , Colombari E. , Menani J. V.
Published: December 2017

This study was performed to investigate the effect of lesion of the anteroventral third ventricle (AV3V) region on the pressor, bradycardic, dipsogenic, natriuretic, kaliuretic, and antidiuretic responses induced by cholinergic activation of the subfornical organ (SFO) in rats. Male Holtzman rats with sham or electrolytic AV3V lesion were implanted with a stainless steel cannula directly into the SFO. Microinjection of the cholinergic agonist carbachol (2 nmol) into the SFO of sham rats induced natriuresis (563 +/- 70 mu eq/120 min), kaliuresis (205 +/- 13 mu eq/120 min), antidiuresis (10.4 +/- 0.5 ml/120 min), water intake (9.3 +/- 1.4 ml/h), bradycardia (-42 +/- 11 beats/min), and increased mean arterial pressure (53 +/- 3 mmHg). In AV3V-lesioned rats (1-5 and 14-18 days), there was a reduction of natriuresis (23 +/- 11 and 105 +/- 26 mu eq/120 min, respectively), kaliuresis (92 +/- 16 and 100 +/- 17 mu eq/120 min), water intake (2.5 +/- 0.9 and 1.8 +/- 1.0 ml/h), and arterial pressure increase (17 +/- 2 and 16 +/- 2 mmHg) induced by carbachol into the SFO. Increased antidiuresis (6.0 +/- 1.0 and 5.2 +/- 0.7 ml/120 min, respectively) and tachycardia (39 +/- 4 and 15 +/- 12 beats/min) instead of bradycardia were also observed in both groups of AV3V-lesioned rats. These results show that cholinergic activation of the rat SFO produces marked natriuresis and kaliuresis in addition to the well-known pressor and dipsogenic responses. They also show that the AV3V region plays an important role in the cardiovascular, fluid, and electrolytic changes induced by cholinergic activation of the SFO in rats.
Sympathetic stimulation alters left ventricular relaxation and chamber size
Authors: Burwash I. G. , Morgan D. E. , Koilpillai C. J. , Blackmore G. L. , Johnstone D. E. , Armour J. A.
Published: December 2017

Alterations in left ventricular (LV) contractility, relaxation, and chamber dimensions induced by efferent sympathetic nerve stimulation were investigated in nine anesthetized open-chest dogs in sinus rhythm. Supramaximal stimulation of acutely decentralized left stellate ganglia augmented heart rate, LV systolic pressure, and rate of LV pressure rise (maximum +dP/dt, 1,809 +/- 191 to 6,304 +/- 725 mmHg/s) and fall (maximum -dP/dt, -2,392 +/- 230 to -4,458 +/- 482 mmHg/s). It also reduced the time constant of isovolumic relaxation, tau (36.5 +/- 4.8 to 14.9 +/- 1.1 ms). Simultaneous two-dimensional echocardiography recorded reductions in end-diastolic and end-systolic LV cross-sectional chamber areas (23 and 31%, respectively), an increase in area ejection fraction (32%), and increases in end-diastolic and end-systolic wall thicknesses (14 and 13%, respectively). End-systolic and end-diastolic wall stresses were unchanged by stellate ganglion stimulation (98 +/- 12 to 95 +/- 9 dyn x 10(3)/cm2; 6.4 +/- 2.4 to 2.4 +/- 0.3 dyn x 10(3)/cm2, respectively). Atrial pacing to similar heart rates did not alter monitored indexes of contractility. Dobutamine and isoproterenol induced changes similar to those resulting from sympathetic neuronal stimulation. These data indicate that when the efferent sympathetic nervous system increases left ventricular contractility and relaxation, concomitant reductions in systolic and diastolic dimensions of that chamber occur that are associated with increasing wall thickness such that LV wall stress changes are minimized.
Glucagon acts in the liver to control spontaneous meal size in rats
Authors: Geary N. , Le Sauter J. , Noh U.
Published: December 2017

To determine the site of origin of pancreatic glucagon's inhibitory effect on spontaneous feeding in rats, glucagon was infused into either the hepatic portal vein or the inferior vena cava during spontaneous meals late in the dark phase. Hepatic portal infusion of 1.7-13.6 micrograms glucagon/meal reduced spontaneous meal size. In contrast, these doses did not significantly affect meal size when delivered via vena caval catheters that ended near the junction of the hepatic vein. This difference indicates that glucagon receptor sites in the liver initiate the satiating action of glucagon during spontaneous meals. The vagal dependency of glucagon satiety was also tested. Hepatic portal infusion of 13.6 micrograms glucagon/meal reduced the size of spontaneous meals both early and late in the dark in neurally intact rats, but not in hepatic-vagotomized rats. Finally, antagonism of endogenous glucagon with hepatic portal infusion of glucagon antibodies in a dose sufficient to neutralize 1 ng glucagon in vitro increased spontaneous meal size in intact rats, but not in hepatic-vagotomized rats. Thus the satiating effects of both exogenous and endogenous glucagon on spontaneous food intake appear to depend on the hepatic branch of the vagus. Taken together, these results are consistent with the hypothesis that glucagon acts in the liver to produce a satiety signal that is transmitted to the brain by the hepatic branch of the abdominal vagus.
Cerebrovascular adaptations to high-altitude hypoxemia in fetal and adult sheep
Authors: Longo L. D. , Hull A. D. , Long D. M. , Pearce W. J.
Published: December 2017

In the fetus and infant, high-altitude hypoxemia is associated with increased cerebrovascular morbidity. To test the hypothesis that this increased morbidity involves changes in cerebrovascular endothelial and smooth muscle function, we examined middle cerebral, posterior communicating, basilar, and common carotid arteries obtained from 23 normoxic fetuses, 19 hypoxemic fetuses maintained at high altitude (3,820 m) from 30 days gestation to near term (approximately 143 days), 55 normoxic non-pregnant adults, and 24 hypoxemic nonpregnant adults maintained at the same altitude and duration as the hypoxemic fetuses. Long-term hypoxemia was associated with several significant changes in both fetal and adult arteries, including a generalized increase in base-soluble protein (5-50%), a depression of the maximum potassium-induced tensions (16-49%), and a depression of the relaxation responses to S-nitroso-N-acetylpenicillamine (1-11%), which releases nitric oxide into solution upon hydration. Altitude acclimatization significantly enhanced amine-to-potassium ratios (the ratio of tension produced by 10 microM serotonin with 20 microM histamine to that produced by 122 mM potassium) only in adult cerebral arteries (51-87%) and significantly depressed potassium-induced stresses (up to 41%) and serotonin/histamine-induced tensions (20-37%) only in fetuses. Endothelium-dependent relaxations to A23187 were significantly depressed in hypoxemic fetuses (4-11%) but were significantly enhanced in hypoxemic adults (2-14%). We conclude that chronic hypoxemia depresses both vascular smooth muscle and endothelial function to a greater extent in fetal than in adult cerebral arteries and that this effect could contribute to the greater postnatal vulnerability to asphyxic and hypertensive insults seen in hypoxemic neonates.
Blood pressure during routine activity, stress, and feeding in black racer snakes (Coluber constrictor)
Authors: Stinner J. N. , Ely D. L.
Published: December 2017

The pressor response to normal daily behaviors and acute stress was studied in black racer snakes (Coluber constrictor) at 30 degrees C. In addition, hematological changes during the stress response were assessed. Mean nighttime systemic arterial blood pressure (SABP) in undisturbed snakes was lower than daytime pressure (26 +/- 3 vs. 32 +/- 9 mmHg, P < 0.001). When snakes were fed mice, SABP increased 3.5- to 4-fold and heart rate increased approximately 3-fold above resting values within approximately 30 s (peak SABP, 99 +/- 18 mmHg; peak heart rate, 99 +/- 12 beats/min). Killing and ingesting the mice required 6-15 min, during which time mean SABP and heart rate were 84 +/- 16 mmHg and 92 +/- 12 beats/min. Pulmonary blood pressure also increased but remained 40-50 mmHg lower than SABP. During stress elicited by tapping the snakes for 5-8 min, heart rate was 94 +/- 6 beats/min but SABP averaged only 44 +/- 11 mmHg. Plasma norepinephrine and epinephrine increased 51- and 26-fold. Plasma glucose increased 58%, hematocrit increased 19%, and plasma volume decreased 19%. It is concluded that blood pressure is markedly affected by behavior and that the sympathetic nervous system appears to play a key role.
Characterization of gonadotropin-releasing hormone receptors in goldfish ovary: variation during follicular development
Authors: Pati D. , Habibi H. R.
Published: December 2017

Gonadotropin-releasing hormone (GnRH) receptors were characterized in the goldfish ovary using an analogue of salmon GnRH ([D-Arg6,Trp7,Leu8,Pro9-NEt]GnRH; sGn-RH-A) as a labeled ligand. Binding of sGnRH-A to goldfish follicular membrane preparation was found to be saturable, reversible, and dependent on time, temperature, tissue concentration, and pH. Addition of unlabeled sGnRH-A displaced the bound 125I-labeled sGnRH-A in a dose-related manner. Hill plot as well as Scatchard analysis indicated the presence of two classes of binding sites, a high-affinity/low-capacity site and a low-affinity/high-capacity site, in the fully mature and less mature goldfish ovary. However, immature goldfish ovary contained only a single class of low-affinity binding sites. The equilibrium association constants (Ka) of the low-affinity sites were found to be similar in all follicular groups. However, there was a tendency for a higher Ka value of the high-affinity sites in the less mature follicles (0.5-0.95 mm) compared with the fully mature follicles (1.11-1.48 mm), although the differences were not statistically significant. Bound 125I-sGnRH-A was also found to be displaceable by sGnRH ([Trp7,Leu8]GnRH) and chicken GnRH-II (cGnRH-II; [His5,Trp7,Tyr8]GnRH), which occur naturally in the goldfish brain. sGnRH-A and cGnRH-II were found to bind with greater affinity than sGnRH to the goldfish ovarian GnRH binding sites.
CCK satiety is differentially mediated by high- and low-affinity CCK receptors in mice and rats
Authors: Weatherford S. C. , Laughton W. B. , Salabarria J. , Danho W. , Tilley J. W. , Netterville L. A. , Schwartz G. J. , Moran T. H.
Published: December 2017

Cholecystokinin-JMV-180 (JMV-180) is an analogue of cholecystokinin C-terminal octapeptide (CCK-8), which has been shown to be an agonist at the proposed CCK pancreatic high-affinity site and a functional antagonist at the pancreatic low-affinity site in rats and to have agonist activity at both high- and low-affinity sites in the mouse. In this study we used JMV-180 to evaluate the potential participation of these two CCK-A sites in the satiety effect of CCK-8 in rats and mice. When tested at doses that ranged from 0.01 to 9.2 mumol/kg, JMV-180 did not reliably affect food intake of solid or liquid test diets in rats. When combined with CCK-8 (3.2 or 8.5 nmol/kg) JMV-180 dose dependently reversed the satiety effect of CCK-8. In contrast to these results in the rat, both JMV-180 (3.7-14.8 mumol/kg) and CCK-8 (1.7-6.8 nmol/kg) dose dependently reduced the intake of 20% sucrose in mice. Both CCK-8- and JMV-180-induced suppression of food intake were attenuated by the CCK-A antagonist MK-329 (24.8 nmol/kg). The results of these studies suggest that agonist activity at sites pharmacologically similar to the CCK pancreatic high-affinity site is not sufficient for expression of CCK satiety, whereas agonist activity at low-affinity-like sites is necessary to reduce food intake. Thus the anorexic activity of CCK appears to be mediated through an interaction with a receptor site pharmacologically similar to the pancreatic low-affinity CCK receptor site.
Defective glucoregulation of brain alpha 2-adrenoceptors in obesity-prone rats
Authors: Levin B. E. , Planas B.
Published: December 2017

Only half the male Sprague-Dawley rats fed high-energy diets develop diet-induced obesity (DIO); the rest are diet resistant (DR). It has been established that rats prone to develop DIO have decreased basal brain alpha 2-adrenoceptor levels compared with DR-prone rats and that DIO- but not DR-prone rats show glucose-induced increases in plasma norepinephrine (NE) levels. Because it has also been shown that alpha 2-adrenoceptors modulate ingestive and autonomic functions and are responsive to changes in plasma glucose levels, we tested the hypothesis that DIO- and DR-prone rats would regulate these receptors differently by using hyperinsulinemic clamping to vary plasma glucose levels. Rats with low glucose-induced plasma NE responses (DR-prone) showed significant positive correlations (r = 0.724-0.919) between plasma glucose levels and alpha 2-adrenoceptor ([3H]paraminoclonidine) binding in 5 of 17 brain areas (anterior, ventromedial, and arcuate hypothalamic nucleus; medial and basomedial amygdalar nucleus) assessed by autoradiographic techniques. Near-significant correlations were also seen in the paraventricular nucleus and lateral hypothalamus. High glucose-induced NE responders (DIO-prone) showed such a correlation only in the arcuate nucleus (r = 0.726). There was little glucoregulation of alpha 1-adrenoceptors. The defective ability of DIO-prone rats to alter brain alpha 2-adrenoceptors to changes in plasma glucose levels might underlie their predisposition to become obese on diets high in sucrose.
The adrenocorticotropic hormone and arginine vasopressin responses to hypercapnia in fetal and maternal sheep
Authors: Chen H. G. , Wood C. E.
Published: December 2017

Previous studies have demonstrated that fetal adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP) are increased during periods of acidemia produced by infusion of acid intravenously or by acidemia secondary to hypovolemia. The purpose of this study was to quantify ACTH and AVP responses to hypercapnic acidemia and to test the role of the peripheral chemoreceptors in the control of these responses. Chronically catheterized fetal sheep were subjected to carotid sinus denervation and bilateral vagotomy or were studied intact. At least 5 days after surgery, fetuses were exposed to a 60-min period of normocapnia or hypercapnia, delivered via a polyethylene bag containing 5-8% CO2 in 21% O2 fitted over the head of the pregnant ewe. Hypercapnia significantly increased fetal arterial PCO2 to 55.2 +/- 1.8 and 55.9 +/- 2.2 mmHg and decreased arterial pH to 7.257 +/- 0.011 and 7.281 +/- 0.010 in intact and denervated fetuses, respectively. Fetal mean arterial blood pressure was decreased slightly in the denervated fetuses during hypercapnia. Fetal plasma AVP was increased in both groups equally, and plasma ACTH and cortisol were increased in the denervated fetuses only. Fetal heart rate was increased significantly in intact but not denervated fetuses. We conclude that respiratory acidemia is a mild stimulus to AVP secretion and that this response is not attenuated by peripheral chemodenervation.
Baroreflex buffering of pressor response to vasopressin is mediated by V1, not V2, receptors in conscious rats
Authors: Shimizu K. , Schwartz J. , McGrath B. P.
Published: December 2017

Arginine vasopressin (AVP) enhances reflex buffering of its own pressor response, thus attenuating its vasoconstrictor potential in vivo. To investigate the extent to which this effect of AVP is mediated by V1 or V2 receptors, mean arterial pressure (MAP) and heart rate (HR) changes were examined in response to graded injections of AVP or [Phe2,Orn8]oxytocin, a potent, selective V1-receptor agonist, in the absence and presence of infusion of [Val4,D-Arg8]VP, a selective V2-receptor agonist. Responses were compared in intact and autonomically blocked conscious rats. During autonomic blockade with methscopolamine and hexamethonium, the pressor sensitivities to AVP and [Phe2,Orn8]oxytocin were similarly increased. Infusion of the V2-receptor agonist had no effect by itself on MAP or HR in conscious intact rats. It also did not alter the pressor responses to the V1 agonist, in either intact or autonomically blocked rats. In the presence of the V2 agonist, the decrease in heart rate induced by the V1 agonist was enhanced. These results indicate that reflex buffering of the pressor response to AVP in the conscious rat is mediated by V1 and not V2 receptors. However, V2 receptors may be involved in modulating the heart rate response to AVP.
Lactate and glucose metabolism in mouse (Mus musculus) and reptile (Anolis carolinensis) skeletal muscle
Authors: Wickler S. J. , Gleeson T. T.
Published: December 2017

The reliance on anaerobic metabolism during exercise in lizards has been the subject of a growing body of literature in activity metabolism. Prior studies have demonstrated that lizards rely more on postexercise lactate to regenerate depleted glycogen stores than do many mammals. These studies prompted an in vitro comparison between the metabolic mechanisms for the handling of lactate and glucose in the muscles of a small mammal and lizard. Hindlimb muscles of Mus and Anolis were stimulated to fatigue and then incubated in the presence of 15 mM lactate and either 5.5 (mice) or 8.5 (anoles) mM glucose. Oxidation rates of lactate and glucose were seven to eight times higher in mice. Both species oxidized more lactate than glucose (8 to 9 times). However, anole muscle showed a preference for lactate as a substrate for glycogenesis, incorporating 1.5 times as much lactate (expressed in glucose equivalents) as glucose. In contradistinction, mice incorporated 2.8 times as much glucose into glycogen as lactate. The quantitative differences in metabolic scope of mammals and reptiles are accompanied by fundamental differences in the capacity and patterns of skeletal muscle metabolism of lactate and glucose.
Role of angiotensin II and prostaglandins in the regulation of uteroplacental blood flow
Authors: Woods L. L.
Published: December 2017

This study was designed to determine the importance of the renin-angiotensin (RAS) and prostaglandin (PG) systems in regulating uteroplacental blood flow (UBF). Our objectives were to determine: 1) whether angiotensin II (ANG II) acts as a vasodilator or purely as a vasoconstrictor in the uteroplacental circulation, and 2) whether this circulation is capable of autoregulation. In chronically instrumented pregnant dogs (41-54 days gestation), ANG II was infused intravenously at increasing doses (8, 16, and 24 ng.kg-1 x min-1). Arterial pressure rose from 108 +/- 6 to 146 +/- 4 mmHg and UBF did not change but uterine vascular resistance (UVR) progressively increased. When the experiment was repeated while servo-controlling uterine arterial pressure, UBF fell at all doses, reaching 62 +/- 7% of control at the highest dose, and UVR increased as before. Meclofenamate (6 mg/kg i.v.) did not alter the dose-response curves. In separate experiments, uterine perfusion pressure was reduced in steps to 55 mmHg. UBF was well autoregulated down to approximately 85 mmHg, and neither captopril (14 micrograms.kg-1 x min-1) nor meclofenamate altered UBF autoregulation. Thus ANG II appears to act as a vasoconstrictor in the uteroplacental circulation and any preservation of UBF during ANG II appears to be due to the increased arterial pressure. Also, in the dog the uteroplacental circulation possesses a mild to moderate degree of autoregulatory capability, which does not appear to be dependent on the RAS or PGs.
Heart rate control in normal and aborted-SIDS infants
Authors: Pincus S. M. , Cummins T. R. , Haddad G. G.
Published: December 2017

Approximate entropy (ApEn), a mathematical formula quantifying regularity in data, was applied to heart rate data from normal and aborted-sudden infant death syndrome (SIDS) infants. We distinguished quiet from rapid-eye-movement (REM) sleep via the following three criteria, refining the notion of REM as more "variable": 1) REM sleep has greater overall variability (0.0374 +/- 0.0138 vs. 0.0205 +/- 0.0090 s, P < 0.005); 2) REM sleep is less stationary (StatAv = 0.742 +/- 0.110) than quiet sleep (StatAv = 0.599 +/- 0.159, P < 0.03); 3) after normalization to overall variability, REM sleep is more regular (ApEnsub = 1.224 +/- 0.092) than quiet sleep (ApEnsub = 1.448 +/- 0.071, P < 0.0001). Fifty percent of aborted-SIDS infants showed greater ApEn instability across quiet sleep than any normal infant exhibited, suggesting that autonomic regulation of heart rate occasionally becomes abnormal in a high-risk subject. There was an association between low ApEn values and aborted-SIDS events; 5 of 14 aborted-SIDS infants had at least one quiet sleep epoch with an ApEn value below the minimum of 45 normal-infant ApEn values.
Regional adrenergic regulation of ion transport across the isolated porcine gallbladder
Authors: Duvall M. D. , O'Grady S. M.
Published: December 2017

The regional transport properties of the porcine gallbladder epithelium were studied using Ussing chambers in which tissues were bathed in porcine Ringer solution. Under basal conditions, tissues from the neck absorbed Na and Cl. Fundic tissues also absorbed Na, but net Cl transport was not different from zero. Serosal norepinephrine (NE; 0.1 microM) stimulated Na and Cl absorption in the neck but only Cl absorption in the fundus. The effects of NE on Na and Cl transport were blocked by pretreatment with yohimbine, suggesting that alpha 2-adrenoceptors mediate the transport-related actions of this neurotransmitter. Serosal isoproterenol (0.1 microM) produced a tetrodotoxin-insensitive, propranolol-sensitive increase in the short-circuit current (Isc) in fundic tissues but not in tissues from the neck. The beta 2-adrenergic agonist salbutamol produced a response similar to that of isoproterenol. However, the beta 1-adrenergic agonist dobutamine had no effect. Isoproterenol was 5.8-fold more potent than salbutamol in increasing the Isc. A possible explanation for the regional effects of beta-agonists is that beta-adrenoceptors are localized to epithelial cells in the fundic region. These results and results obtained previously suggest regional differences in basal Na and Cl transport across the porcine gallbladder epithelium and that both alpha 2- and beta 2-adrenoceptors act to regulate ion transport in this tissue.
Effects of estrogen on gluconeogenesis and related parameters in male rainbow trout
Authors: Washburn B. S. , Krantz J. S. , Avery E. H. , Freedland R. A.
Published: December 2017

To investigate the effects of estrogen, the hormone responsible for vitellogenesis, on gluconeogenesis, male rainbow trout were implanted with 17 beta-estradiol or given a sham procedure. Plasma glucose concentration in estrogenized fish was 50% of the control fish (6.4 mM). Glucose synthesis from physiological concentrations of alanine was 0.08 mumol.g cells-1 x h-1 compared with 0.20 mumol.g cells-1 x h-1 in control fish; synthesis from physiological concentrations of lactate was reduced by over 50% (0.88 vs. 0.36 mumol.g cells-1 x h-1) in implanted fish. Gluconeogenesis from 5 mM lactate was also significantly depressed in implanted fish. Oxidation of alanine, serine, and lactate was not significantly affected by estrogen implantation. The maximum clearance velocity of a key enzyme negatively regulating gluconeogenesis, pyruvate kinase, was 3.03 mumol.g cells-1 x h-1 in estrogen (E2) implanted fish compared with 7.83 mumol.g cells-1 x h-1 in control fish. No significant differences in plasma insulin or glucagon were found in the two groups. We conclude that estrogen depresses gluconeogenesis and that this reduction contributes to the lower plasma glucose concentration seen in vitellogenic trout.
Changes in extracellular [K+] and [Ca2+] induced by anoxia in neonatal rabbit medulla
Authors: Morris M. E. , Trippenbach T.
Published: December 2017

Ion-selective microelectrodes were used to record levels of extracellular K+ and Ca2+ concentrations ([K+]o and [Ca2+]o, respectively) and the changes evoked by anoxia in the medulla of anesthetized ventilated newborn rabbits, 1-14 days of age. Resting levels of [K+]o showed significant decline with increasing age. The mean initial level of [K+]o was 6.5 +/- 0.3 mM for the 1st neonatal wk and 5.1 +/- 0.4 mM for the 2nd wk. Brief periods of N2 inhalation (1-3 min) induced reversible increases in [K+]o that were smaller with progression of maturity. The duration of the initial increase (phase I) in [K+]o was twofold greater during the 1st wk than the 2nd wk. At the maximal steady-state level of change (phase III), [K+]o increased by 1.8 +/- 0.2 mM during wk 1 and by 0.9 +/- 0.1 mM during wk 2. Large transient bursts of increase were frequently observed during both early and recovery phases of the sustained [K+]o accumulation. Resting levels of [Ca2+]o also showed age dependence. The mean values during early neonatal days 1-3, compared with days 7-10, were 3.7 +/- 0.3 and 2.4 +/- 0.6 mM, respectively. Anoxia evoked multiphasic decreases in [Ca2+]o that were largest in the youngest pups. Early transient falls of 0.5 +/- 0.1 mM occurred at times similar to those for the earliest increases of [K+]o and negative focal potentials; larger decreases (0.9 +/- 0.2 mM) were recorded after reoxygenation.(ABSTRACT TRUNCATED AT 250 WORDS)
A mathematical model of oscillatory insulin secretion
Authors: Berman N. , Chou H. F. , Berman A. , Ipp E.
Published: December 2017

Insulin is secreted in sustained oscillatory fashion from isolated islets of Langerhans. This finding has led to the assumption of an underlying synchronizing process that coordinates insulin oscillations. This assumption was tested by developing a mathematical model of oscillatory insulin secretion in which we included degree of synchrony as a parameter. We first evaluated insulin oscillations in perifused isolated rat islets, using spectral analysis to determine their regularity and frequency. A parsimonious mathematical model was developed to account for these characteristics. The model postulates a group of secretory units discharging at discrete intervals with the same underlying period. Variation from two sources, phase differences between units (synchrony) and regularity within units, is introduced by adding two normally distributed random variables with standard deviations (Sg and Si, respectively) to the secretory period. Sets of 100 simulations for different values of Sg and Si were run. Results of the simulations suggest that the system tolerates a relatively large degree of asynchrony yet still demonstrates regularity of oscillations on spectral analysis. Comparison with perifusion data suggests that a moderate degree of asynchrony between islets can best account for the pattern of insulin oscillations observed. This model provides a theoretical basis for the study of mechanisms for insulin oscillations.
Cholecystokinin octapeptide decreases food intake in white-crowned sparrows
Authors: Richardson R. D. , Boswell T. , Weatherford S. C. , Wingfield J. C. , Woods S. C.
Published: December 2017

White-crowned sparrows maintained on short days (9:15-h light-dark cycle) were peripherally injected with 1.0, 4.0, and 16 micrograms/kg ip of cholecystokinin octapeptide (CCK-8). Meal size over the subsequent 30 min was significantly depressed in a dose-dependent fashion. Water intake was not affected. The anorexic effect caused by 4.0 micrograms/kg was attenuated by 100 micrograms/kg of the type-A CCK receptor antagonist MK-329 but not by 300 micrograms/kg of the type-B CCK receptor antagonist L 365,260, suggesting that CCK-induced suppression of food intake in this species is mediated by a CCK-A receptor. Administration of both CCK-A and CCK-B receptor antagonists alone resulted in no change in meal size. These experiments suggest that white-crowned sparrows, when weight stable, respond to CCK-8 in a manner comparable with several mammalian species.
Protective effect of vitamin E on exercise-induced oxidative damage in young and older adults
Authors: Meydani M. , Evans W. J. , Handelman G. , Biddle L. , Fielding R. A. , Meydani S. N. , Burrill J. , Fiatarone M. A. , Blumberg J. B. , Cannon J. G.
Published: December 2017

The protective effect of vitamin E supplementation on exercise-induced oxidative damage was tested in 21 male volunteers. Nine young (22-29 yr) and 12 older (55-74 yr) sedentary male subjects participated in a double-blind protocol and received either 800 IU dl-alpha-tocopherol or a placebo daily. After 48 days, vitamin E supplementation significantly increased alpha-tocopherol in plasma and skeletal muscle. Subjects then performed a bout of eccentric exercise at 75% of their maximum heart rate by running down an inclined treadmill for 45 min. All vitamin E-supplemented subjects excreted less (P < 0.05) urinary thiobarbituric acid adducts after the exercise bout than placebo subjects at 12 days postexercise (35 and 18% above baseline in young and old supplemented groups, respectively, vs. 60 and 80% in young and old placebo groups, respectively). After exercise, the initial difference in alpha-tocopherol concentration of muscle between young placebo and vitamin E-supplemented groups was diminished and muscle lipid conjugated dienes tended to increase (P = 0.09) in placebo subjects. Placebo subjects had a significant decrease in major fatty acids of muscle biopsy taken immediately after exercise. When normalized for the hemoconcentration effects of exercise, the plasma concentration of vitamins E and C and uric acid showed no significant change. The alterations in fatty acid composition, vitamin E, and lipid conjugated dienes in muscle and in urinary lipid peroxides in controls after eccentric exercise are consistent with the concept that vitamin E provides protection against exercise-induced oxidative injury.
Modulation of release of [3H]acetylcholine in the major pelvic ganglion of the rat
Authors: Somogyi G. T. , de Groat W. C.
Published: December 2017

Cholinergic modulation of [3H]acetylcholine release evoked by electrical stimulation was studied in the rat major pelvic ganglion, which was prelabeled with [3H]choline. Acetylcholine (ACh) release was independent of the frequency of stimulation; 0.3 Hz produced the same volley output as 10 Hz. Tetrodotoxin (1 microM) or omission of Ca2+ from the medium abolished ACh release. The M1 receptor agonist (4-hydroxy-2-butynyl)-1-trimethylammonium m-chlorocarbanilate chloride (McN-A 343, 50 microM) increased release (by 136%), whereas the M2 muscarinic agonist oxotremorine (1 microM) decreased ACh release (by 22%). The muscarinic antagonists, atropine (1 microM) or pirenzepine (M1 selective, 1 microM), did not change ACh release. However, pirenzepine (1 microM) blocked the facilitatory effect of McN-A 343, and atropine (1 microM) blocked the inhibitory effect of oxotremorine. The cholinesterase inhibitor physostigmine (1-5 microM), the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP, 10 microM), and the nicotinic antagonist D-tubocurarine (50 microM) did not change ACh release. 4-Aminopyridine, a K+ channel blocker, significantly increased the release (by 146%). Seven days after decentralization of the major pelvic ganglion, the evoked release of ACh was abolished. It is concluded that release of ACh occurs from the preganglionic nerve terminals rather than from the cholinergic cell bodies and is not modulated by actions of endogenous ACh on either muscarinic or nicotinic autoreceptors. These data confirm and extend previous electrophysiological findings indicating that synapses in the major pelvic ganglion have primarily a relay function.
Dorsal root afferent influences on tonic firing of renal and mesenteric sympathetic nerves in rats
Authors: Taylor R. B. , Weaver L. C.
Published: December 2017

After spinal cord transection in cats and rats, the activity of many sympathetic nerves is not entirely lost, and firing of other nerves continues unabated or is increased. This study was done to evaluate the importance of dorsal root afferent discharge on the generation of tonic sympathetic activity in renal and mesenteric postganglionic nerves in spinal rats and in rats with intact neuraxes. Sympathetic discharge was recorded in anesthetized rats, and peripheral afferent influences were eliminated by dorsal rhizotomy from T4 to L2. Activity of renal and mesenteric nerves was well maintained after high cervical and thoracic (T4) cord transections. Rhizotomy had no effect on sympathetic discharge in rats with intact neuraxes but decreased renal nerve activity significantly (-25%) in spinal rats. Because rhizotomy decreased mesenteric discharge in only three of six spinal rats, mean mesenteric nerve discharge was not decreased significantly. The decreased renal nerve discharge after dorsal rhizotomy could not be attributed to input from any specific spinal segment, and ipsilateral input was no greater than contralateral input. After rhizotomy, both renal and mesenteric nerves had substantial excitatory drive from the transected, deafferented spinal cord. These findings demonstrate that dorsal root afferent influences on spinal neurons can contribute to the generation of tonic discharge in some sympathetic nerves in spinal animals.
Prostanoid cascade inhibition prevents cardiovascular and adrenocorticotropic responses to mineral acid infusion
Authors: Cudd T. A. , Wood C. E.
Published: December 2017

Mineral acid infusion is used to investigate the effects of acidemia on the cardiovascular and respiratory systems. Previous studies have shown that small infusions of HCl increase mean arterial pressure (MAP), adrenocorticotropic hormone (ACTH), and cortisol without producing acidemia. We infused 1 meq/min of 1 N HCl intravenously into chronically catheterized conscious sheep with or without pretreatment with 1.1 mg/kg flunixin-N-methylglucamine, a cyclooxygenase inhibitor (n = 6). Acid infusion resulted in significant increases in heart rate (83 +/- 5 to 94 +/- 7 beats/min), MAP (84 +/- 3 to 104 +/- 6 mmHg), ACTH (97 +/- 23 to 285 +/- 101 pg/ml), cortisol (20 +/- 3 to 37 +/- 16 ng/ml), sodium (149.5 +/- 0.8 to 150.6 +/- 1.3 meq/l), potassium (3.96 +/- 0.09 to 4.31 +/- 0.19 meq/l), and thromboxane (Tx) B2 (stable metabolite of TxA2) (147 +/- 78 to 2,304 +/- 1,213 pg/ml), whereas these changes were prevented by flunixin. Plasma concentrations of 6-ketoprostaglandin F1 alpha (stable metabolite of prostacyclin), prostaglandin E2, interleukin-1 alpha, and hematocrit did not change in either group. Arterial pH decreased, whereas arterial partial pressure of CO2 increased significantly in both groups. Arterial partial pressure of O2 declined in both groups, but the decrease was significantly greater in the group not receiving flunixin. We conclude that a cyclooxygenase metabolite, most likely TxA2, mediates the MAP, heart rate, ACTH, and cortisol responses to mineral acid infusion.
Role of endothelium-derived nitric oxide in hemodynamic adaptations after graded renal mass reduction
Authors: Griffin K. A. , Bidani A. K. , Ouyang J. , Ellis V. , Churchill M. , Churchill P. C.
Published: December 2017

The mediator(s) of the adaptive increases in renal blood flow (RBF) and glomerular filtration rate (GFR) after renal mass reduction have not been identified. The present studies were designed to investigate the role of endothelium-derived nitric oxide (EDNO) in the hemodynamic adaptations after graded renal mass reduction. The experiments were performed in rats that had undergone a sham reduction in renal mass, uninephrectomy (UNX), or 5/6 NX (UNX plus excision of both poles of the contralateral kidney) 3-4 wk before. Measurements of RBF, GFR, renal vascular resistance (RVR), mean arterial pressure (MAP), and plasma renin concentration (PRC) were obtained before and after administration of the EDNO synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA). L-NMMA (50 mg/kg bolus plus 500 micrograms.kg-1.min-1 infusion) led to significant (P < 0.01) and comparable increases in MAP (mmHg) (P < 0.01) in sham rats (117 +/- 6 to 154 +/- 6), UNX rats (112 +/- 5 to 139 +/- 7), and 5/6 NX rats (116 +/- 5 to 149 +/- 7). RVR increased significantly in all three groups (P < 0.01). The resultant decrease in RBF (ml.min-1.kg-1) was similar in sham rats (34.9 +/- 2.6 to 23.8 +/- 1.6), UNX rats (43.9 +/- 3.6 to 27.3 +/- 2.8), and 5/6 NX rats (34.6 +/- 2 to 22.3 +/- 1.6) (P < 0.01 for all groups).(ABSTRACT TRUNCATED AT 250 WORDS)
Acute phase response in exercise. III. Neutrophil and IL-1 beta accumulation in skeletal muscle
Authors: Fielding R. A. , Manfredi T. J. , Ding W. , Fiatarone M. A. , Evans W. J. , Cannon J. G.
Published: December 2017

Nine untrained men (22-29 yr) performed 45 min of downhill running (16% incline, 70% of maximum heart rate). Needle biopsies of the vastus lateralis were performed before, 45 min after, and 5 days after exercise. Immunohistochemical staining of muscle cross sections revealed a 135% increase in muscle interleukin-1 beta (IL-1 beta) immediately after and a 250% increase (P < 0.03) 5 days after exercise. Using a rating scale (0-3) for the presence of neutrophils, light microscopic examination showed a significant accumulation of neutrophils in muscle biopsies taken 45 min after and 5 days after exercise [before: 0.5 +/- 0.2, 45 min after: 1.5 +/- 0.3 (P < 0.01), and 5 days after: 1.2 +/- 0.2 (P < 0.04)]. In addition, electron microscopic analysis showed an increase in the percentage of damaged Z-bands relative to total Z-bands [before: 4.8 +/- 3.5%, 45 min after: 32.5 +/- 8.6% (P < 0.05), and 5 days after: 14.1 +/- 3.2%]. Neutrophil accumulation was positively correlated to intracellular Z-band damage (rho = 0.66, P < 0.001). Immunohistochemical staining for IL-1 beta was related to neutrophil accumulation in muscle (rho = 0.38, P < 0.06) and to plasma creatine kinase levels (rho = 0.416, P < 0.04). These data indicate that after eccentric exercise ultrastructural damage to skeletal muscle is associated with neutrophil infiltration and muscle IL-1 beta accumulation.