bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal modulation of channel catfish intestinal dimensions, BBM fluidity, and glucose transport
Authors: Houpe K. L. , Malo C. , Oldham P. B. , Buddington R. K.
Published: December 2017

In light of the direct influence of temperature on metabolic rates and dietary loads of ectotherms, intestinal responses were evaluated by measuring 1) dimensions, 2) transapical initial rates of transport using intact tissues and brush-border membrane vesicles (BBMV), and 3) BBMV fluidity using two size groups of channel catfish (Ictalurus punctatus) acclimated to different water temperatures. Intestines of larger fish at 15 degrees C were 23% longer and 61% heavier than those at 30 degrees C. Regardless of assay temperature, rates of glucose uptake by fish held at 30 degrees C relative to those at 15 degrees C were twofold higher for intact tissues and over fivefold higher for BBMV. Although rates of PBMV transport were higher for smaller fish, adaptive responses were greater for larger fish. Temperature coefficients (Q10S) for BBMV transport were higher between 5 and 15 degrees C (3.5-4.5) relative to 15 to 35 degrees C (1.9-2.0) and may be partly related to the inability of catfish held at low temperatures to adjust apical membrane fluidity. Our findings indicate that 1) cold-acclimated catfish maintain transport capacities by increasing intestinal dimensions, 2) high acclimation temperatures increase rates of uptake by as yet unknown mechanisms, 3) thermal modulation of transport varies among species and nutrients, and 4) adaptive responses of ectotherms are different from those of homeotherms).
Effects of NO on baroreflex control of heart rate and renal nerve activity in conscious rabbits
Authors: Liu J. L. , Murakami H. , Zucker I. H.
Published: December 2017

Recent data suggest that nitric oxide (NO) plays a role in the modulation of sympathetic nerve activity and baroreflex sensitivity. Most of these studies have been carried out in anesthetized preparations, and little if any comparison has been made on the relative role of NO on the baroreflex control of heart rate and sympathetic nerve activity. In the present studies, the effect of the NO synthase inhibitor NG-nitro-L-arginine (L-NNA) on the baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) were investigated in conscious, instrumented rabbits. Intravenous bolus injections of 13 mg/kg of L-NNA decreased baseline HR (from 205.0 +/- 6.0 to 145.5 +/- 8.2 beats/min; P < 0.05) without significant changes in mean arterial pressure (MAP) and RSNA. L-NNA significantly reduced the lower plateau of the HR-MAP curves and increased the sensitivities of baroreflex control of HR and RSNA. L-Arginine (600 mg/kg i.v.) but not D-arginine reversed the above effects. The effects of L-NNA on baseline HR were not completely blocked by metoprolol (2 mg/kg) or by atropine (0.2 mg/kg). After pretreatment with metoprolol, baroreflex sensitivity was reduced and L-NNA increased baroreflex sensitivity back to the control level. After pretreatment with atropine, L-NNA still reduced the lower plateau but did not significantly affect baroreflex sensitivity. L-NNA increased the HR responses but not the RSNA response to electrical stimulation of the aortic nerve in chloralose-anesthetized, sinoaortic-denervated (SAD) rabbits. L-NNA had no effect on the HR response to right vagal stimulation. In both conscious intact and SAD rabbits, L-NNA did not increase baseline RSNA. These results suggest that endogenous NO decreases baroreflex control of HR and RSNA. Both sympathetic and parasympathetic components play a role in the effects of NO on the baroreflex control of HR. The effects of NO in the central nervous system play a more important role in the baroreflex control of HR than of RSNA.
Inhibition of stimulated and basal ACTH by cortisol during ovine pregnancy
Authors: Keller-Wood M.
Published: December 2017

In pregnant ewes, as in pregnant women, plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations are increased. Inhibition of free cortisol concentrations by dexamethasone, a synthetic glucocorticoid, is reduced in pregnant women compared with nonpregnant women. These experiments were designed to test the hypothesis that basal and stimulated ACTH concentrations are less sensitive to negative feedback inhibition by cortisol in pregnant ewes than in nonpregnant ewes. Ewes were infused with vehicle and with cortisol at two different rates (1 and 2 micrograms.kg-1.min-1) for 1 h; plasma ACTH concentrations during and after the infusion and after subsequent stimulation by hypotension were measured. Basal plasma ACTH concentrations during a 2-h infusion of cortisol (2 micrograms.kg-1.min-1) were also measured in undisturbed ewes. Cortisol significantly inhibited both stimulated and basal ACTH. The degree of suppression of ACTH was not reduced in the pregnant ewes compared with the nonpregnant ewes. The results indicate that both basal and stimulated ACTH are sensitive to negative feedback inhibition by cortisol during ovine pregnancy.
Human immunodeficiency virus envelope glycoprotein 120 alters sleep and induces cytokine mRNA expression in rats
Authors: Opp M. R. , Rady P. L. , Hughes T. K. , Cadet P. , Tyring S. K. , Smith E. M.
Published: December 2017

Pages R963–R970: M. R. Opp, P. L. Rady, T. K. Hughes, Jr., P. Cadet, S. K. Tyring, and E. M. Smith. “Human immunodeficiency virus envelope glycoprotein 120 alters sleep and induces cytokine mRNA expression in rats.” On p. R968, Fig. 3 should appear as below.

(See PDF)
In the Lyon hypertensive rat, renal function alterations are angiotensin II dependent
Authors: Liu K. L. , Sassard J. , Benzoni D.
Published: December 2017

To assess the role of the renin-angiotensin system (RAS) in the renal alterations of the lyon hypertensive (LH) rat, the renal function of LH rats and of their normotensive (LN) controls was studied at different pressure levels after an early and chronic blockade of the RAS by perindopril (3 mg.kg-1.day-1 orally from 3 to 15 wk of age) and after an acute infusion of angiotensin II (ANG II, 10 or 50 ng.kg-1.min-1). Over the range of renal perfusion pressures studied (115-165 mmHg), control LH differed from LN rats by an increased preglomerular vasoconstriction and a blunted pressure-natriuresis curve. Perindopril fully prevented the development of hypertension in LH rats, suppressed their preglomerular vasoconstriction, and markedly improved their pressure-natriuresis. In perindopril-treated LH, ANG II produced a greater reduction in renal blood flow, glomerular filtration rate, and urinary sodium excretion that was not significantly modified by blockade of thromboxane A2-prostaglandin H2 receptors. These results indicate that the blood pressure level and the renal function of LH rats are closely dependent on an active RAS.
5-HT in DVC: disparate effects on TRH analogue-stimulated gastric acid secretion, motility, and cytoprotection
Authors: Chi J. , Kemerer J. , Stephens R. L.
Published: December 2017

Convergent evidence suggests that thyrotropin-releasing hormone (TRH) is a principal regulator of several vagally mediated gastric responses. Serotonin (5-HT) interacts with TRH in the dorsal vagal complex (DVC) to augment gastric acid secretory responses. This study investigated the ability of 5-HT to alter other gastric responses mediated by TRH administration into the DVC. Co-injection of 5-HT (7.9 pmol) and the TRH analogue RX-77368 (0.66 pmol) produced a 117% enhancement in 1-h gastric acid output compared with rats treated with RX-77368 (0.66 pmol) alone into the DVC. In contrast, coadministration of RX-77368 (4 pmol) with various doses of 5-HT (0.0048-480 pmol) was ineffective in significantly altering stimulation of gastric antral motility produced by RX-77368 (4 pmol) alone. The effect of a lower dose of DVC RX-77368 (0.66 pmol) on gastric motility was also not changed by 5-HT coadministration. Moreover, the cytoprotective effect of DVC RX-77368 (1.5 pmol) on oral ethanol-induced gastric mucosal lesions was reversed by 5-HT coadministration (54 or 18 pmol). The results suggest that activation of 5-HT receptors in the DVC can augment, not affect, and attenuate DVC TRH analogue-stimulated gastric acid secretion, antral motility, and cytoprotection, respectively.
Alterations in myometrial stress during ovine pregnancy and the puerperium
Authors: Ipson M. A. , Rosenfeld C. R. , Magness R. R. , Kamm K. E.
Published: December 2017

Substantial alterations occur in female reproductive tissues to ensure the successful outcome of and recovery from pregnancy. Although sheep have been widely used to study several aspects of pregnancy, little information is available regarding alterations in myometrial function. We therefore characterized the alterations that occur in ovine myometrial stress-generating capacity and examined mechanisms that might account for these changes. Length-force relations were determined for longitudinal myometrial strips from nonpregnant (n = 6), pregnant (n = 11; 67-140 days gestation), and postpartum (n = 6) ewes. Active stress (force per cross-sectional area) was calculated at optimal length for maximal force as determined from length-force relations. Stimulation by 65 mM KCl resulted in 3.5 times greater stress in strips from late-pregnant vs. nonpregnant ewes, 1.20 +/- 0.16 vs. 0.34 +/- 0.04 x 10(5) N/m2 (+/- SE; P < 0.05), respectively. Responses returned to values seen in strips from nonpregnant ewes within 2 wk postpartum. Increases in stress were not associated with differences in the phosphorylated myosin light-chain fraction or the amount of smooth muscle bundles. Although basal prostacyclin production was 15-fold greater in myometrium from nonpregnant vs. pregnant ewes (222 +/- 28 vs. 14.9 +/- 2.0 pg.mg wet wt-1.h-1), cyclooxygenase inhibition did not potentiate stress responses in strips from nonpregnant animals. However, smooth muscle contents of actin (26.0 +/- 1.8 vs. 19.1 +/- 2.2 micrograms/mg wet wt) and myosin heavy chain (5.5 +/- 0.4 vs. 2.0 +/- 0.3 microgram/mg wet wt) were greater (P < 0.04) in myometrium from late-pregnant vs. nonpregnant ewes. Myometrial growth during ovine pregnancy is associated with reversibly augmented contractile properties that appear to primarily reflect increased cellular contents of contractile proteins.
Female reproductive cycle influences plasma volume and protein restitution after hemorrhage in the conscious rat
Authors: Slimmer L. M. , Blair M. L.
Published: December 2017

The present study was designed to test the hypothesis that gender and female reproductive cycle phase influence the restitution of blood volume following blood loss. The experiments were performed in conscious 9- to 11-wk-old Sprague-Dawley rats subjected to a slow hemorrhage of 19 ml/kg over 40 min. The effect of hemorrhage was compared in male rats and in female rats in either proestrus (Pro) or metestrus (Met). In comparison with either metestrus females or males, females hemorrhaged on the morning of proestrus showed a significantly larger overall decrease in percent hematocrit (Pro, -17 +/- 1; Met, -10 +/- 1; male, -13 +/- 1; mean +/- SE), increase in plasma volume (Pro, to 151 +/- 15% of initial volume; Met, 104 +/- 8%; male, 120 +/- 4%), and increase in total plasma protein content (Pro, to 164 +/- 14% of initial content; Met, 101 +/- 5%; male, 132 +/- 5%) over the 21-h posthemorrhage recovery period. Proestrus females also showed a larger increase in plasma osmolality during the first 2.5-h posthemorrhage than either metestrus females or males (P < 0.05). In addition, basal hematocrit and total blood volume (51Cr-tagged erythrocyte method) were higher in females studied on the morning of proestrus than in metestrus females. These results indicate that the female reproductive cycle is an important variable in basal blood volume regulation and in plasma protein and plasma volume restitution following blood loss.
Pregnancy-associated sleep changes in the rat
Authors: Kimura M. , Zhang S. Q. , Inoue S.
Published: December 2017

Sleep disorder during the course of pregnancy has been recently recognized in humans. However, the underlying mechanism of pregnancy-associated sleep disorder remains undetermined, and sleep changes even during normal pregnancy have not been fully understood. To describe the effects of pregnancy on sleep, sleep-wake patterns before and after fertile mating were compared in an animal model. Baseline recordings of sleep and brain temperature were made throughout a normal 4-day estrous cycle in female rats. After the rats became pregnant, the recordings continued across the entire pregnant period. Compared with baseline sleep before mating, both non-rapid eye movement sleep and rapid eye movement sleep increased significantly from the first night of pregnancy. Although rapid eye movement sleep returned to the baseline level from midpregnancy, nocturnal non-rapid eye movement sleep stayed enhanced during the entire pregnant period. Daytime sleep fluctuated toward the end of pregnancy. Brain temperature was elevated during the early period of pregnancy but did not correlate with enhanced sleep. The results suggest that physiological changes in different stages of pregnancy may contribute to the regulation of maternal sleep and temperature.
Application of acute maximal exercise to protect orthostatic tolerance after simulated microgravity
Authors: Engelke K. A. , Doerr D. F. , Crandall C. G. , Convertino V. A.
Published: December 2017

We tested the hypothesis that one bout of maximal exercise performed at the conclusion of prolonged simulated microgravity would improve blood pressure stability during an orthostatic challenge. Heart rate (HR), mean arterial blood pressure (MAP), norepinephrine (NE), epinephrine (E), arginine vasopressin (AVP), plasma renin activity (PRA), atrial natriuretic peptide (ANP), cardiac output (Q), forearm vascular resistance (FVR), and changes in leg volume were measured during lower body negative pressure (LBNP) to presyncope in seven subjects immediately prior to reambulation from 16 days of 6 degrees head-down tilt (HDT) under two experimental conditions: 1) after maximal supine cycle ergometry performed 24 h before returning to the upright posture (exercise) and 2) without exercise (control). After HDT, the reduction of LBNP tolerance time from pre-HDT levels was greater (P = 0.041) in the control condition (-2.0 +/- 0.2 min) compared with the exercise condition (-0.4 +/- 0.2 min). At presyncope after HDT, FVR and NE were higher (P < 0.05) after exercise compared with control, whereas MAP, HR, E, AVP, PRA, ANP, and leg volume were similar in both conditions. Plasma volume (PV) and carotid-cardiac baroreflex sensitivity were reduced after control HDT, but were restored by the exercise treatment. Maintenance of orthostatic tolerance by application of acute intense exercise after 16 days of simulated microgravity was associated with greater circulating levels of NE, vasoconstriction, Q, baroreflex sensitivity, and PV.
Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats
Authors: Tang-Christensen M. , Larsen P. J. , Goke R. , Fink-Jensen A. , Jessop D. S. , Moller M. , Sheikh S. P.
Published: December 2017

Glucagon-like peptide (GLP)-1-(7-36) amide and its pancreatic receptors are important for control of blood glucose levels. However, rat GLP-1 receptors are also localized in the brain, in hypothalamus, and in areas without a blood-brain barrier. When rats were kept on a food restriction schedule, intracerebroventricular injection of GLP-1 just before food was offered inhibited food intake. However, peripheral GLP-1 administration by intraperitoneal injection had little effect. GLP-1 effects on water intake and output were also investigated. Intracerebroventricular GLP-1 profoundly inhibited angiotensin II-induced drinking behavior in rats, and water intake was suppressed by exogenous GLP-1 in rats habituated to a water restriction schedule. These effects were reproduced by intraperitoneal administration of GLP-1. Furthermore, intracerebroventricular GLP-1 stimulated urinary excretion of water and sodium. The centrally elicited effects were blocked by the GLP-1 antagonist exendin-(9-39) amide, whereas the N-terminally extended and inactive GLP-1-(1-36) amide had no effect on feeding and drinking. GLP-1 had no effect in behavioral assays measuring exploratory locomotor activity and conditioned taste aversion. In conclusion, GLP-1 may play a physiological role in regulation of both ingestion and the water and salt homeostasis.
Hepatic capillary pressure is estimated using triple vascular occlusion method in isolated canine liver
Authors: Shibamoto T. , Wang H. G. , Tanaka S. , Koyama S.
Published: December 2017

We determined whether the triple vascular occlusion pressure (Pto), the equilibration pressure obtained when the hepatic artery, portal, and hepatic veins were occluded simultaneously, represented the capillary pressure (Pc) in isolated bivascularly blood-perfused canine livers. Effects of a bolus injection of histamine (0.1-60 micrograms), norepinephrine (NE; 1-600 micrograms), or acetylcholine (ACh; 0.01-10 micrograms) into the portal vein or the hepatic artery were also studied on vascular resistance distribution using Pto as a measure of Pc. The livers were perfused at constant flow via the portal vein and at constant pressure via the hepatic artery. Pto was compared with Pc measured using the traditional gravimetric method (Pc,i). Pto and Pc,i showed a strong correlation (Pto = -0.02 + 0.98 Pc,i; r = 0.83, P = 0.0018). With comparisons, the intercept was not significantly different from zero, and the slope was not different from 1.00, indicating that Pto accurately represented Pc. The resting postsinusoidal vascular resistance comprised 54% of the total hepatic vascular resistance (Rt). Portal or arterial injection of histamine increased predominantly hepatic venous resistance (Rhv) over portal resistance with liver weight gain. NE constricted both the portal vein and the hepatic artery in greater magnitude than the hepatic vein, as evidenced by a significant decrease in the Rhv/Rt ratio. This precapillary constriction was accompanied by a significant decrease in liver weight. In contrast, ACh contracted both portal and hepatic veins similarly without liver weight change. We conclude that Pto is an excellent estimate of Pc in isolated blood-perfused canine livers and that the hepatic vascular resistance sites in the resting states are located evenly in the pre- and postsinusoidal vessels. Intraportal or intra-arterial infusion of histamine, NE, and ACh produced characteristically different changes in hepatic vascular resistances and hepatic volume. The Pto technique could be applied in experimental research on hepatic hemodynamics.
Inhibitors of cytochrome P-450 augment fever induced by interleukin-1 beta
Authors: Nakashima T. , Harada Y. , Miyata S. , Kiyohara T.
Published: December 2017

Metabolites of cytochrome P-450 are produced in cells when arachidonic acid cascade is activated. Fever genesis depends largely on the cyclooxygenase branch of arachidonic acid cascade, which is caused by many stimuli, such as interleukin (IL)-1, IL-6, and interferon-alpha. To assess the significance of cytochrome P-450 branch in fever, murine recombinant IL-1 beta was bilaterally microinjected (1 ng/microliter) into the medial preoptic area and anterior hypothalamus in conscious rats treated 60 min previously with or without the cytochrome P-450 inhibitor econazole (15 mg/kg im). The IL-1 beta-induced rise in colonic temperature was enhanced after the plateau phase of fever (from 240 min after IL-1 beta) in econazole-pretreated rats (P < 0.001). Another cytochrome P-450 inhibitor, clotrimazole (15 mg/kg im), also enhanced IL-1 beta-induced fever from 160 min after IL-1 beta injection (P < 0.001). Econazole also enhanced the fever when it was given 120 min before injection of IL-1 beta (P < 0.001). The cytochrome P-450 inhibitor, however, did not affect the fever when given 10 min after IL-1 beta (P = 0.95). Econazole and clotrimazole did not alter normal body temperature (P = 0.65 and 0.73, respectively). The results suggest that the metabolite(s) of cytochrome P-450 affect the falling phase after the plateau phase of fever and act as putative endogenous antipyretic(s).
Regulation of skeletal muscle metabolism in the lizard Dipsosaurus dorsalis by fructose-2,6-bisphosphate
Authors: Scholnick D. A. , Gleeson T. T.
Published: December 2017

Changes in liver and skeletal muscle fructose-2,6-bisphosphate (Fru-2,6-P2) concentrations were compared during fasting, exercise, and recovery in the lizard Dipsosaurus dorsalis and in outbred mice (Mus musculus). We present the first correlative evidence that suggests that a decrease in the content of Fru-2,6-P2 may mediate elevated gluconeogenesis in lizard skeletal muscle. Contents of Fru-2,6-P2 in lizard gastrocnemius and red and white iliofibularis (IF) were significantly lower (as much as 55% in white IF) during recovery from exhaustive exercise than at rest. Recovery from exhaustive exercise had no significant effect on Fru-2,6-P2 concentrations in any mouse muscle examined. Fasting significantly depressed lizard and mouse liver Fru-2,6-P2 contents and decreased lizard red IF by over 84% from the fed condition. Lizard red and white muscle fiber bundles incubated in 20 mM lactate had significantly lower Fru-2,6-P2 (94 and 61% depression, respectively) than those incubated in 8.5 mM glucose. These results are consistent with the hypothesis that Fru-2,6-P2 acts as a signal for controlling gluconeogenesis in lizard skeletal muscle.
Water transport in collecting ducts of Japanese quail
Authors: Nishimura H. , Koseki C. , Patel T. B.
Published: December 2017

Previously, we reported that the countercurrent urine concentration mechanism in birds appears to operate by recycling of a single solute (NaCl), in which the thick ascending limb of looped nephrons provides an energy source. To determine the importance of the medullary collecting duct (MCD) in the countercurrent multiplier system, we examined in isolated and perfused MCDs from Japanese quail, Coturnix coturnix, the osmotic and/or diffusional water permeability and whether arginine vasotocin (AVT) regulates water permeability. We noted that dark cells that possess electron-dense cytoplasm and numerous mitochondria and light mucus-secreting cells exist in the cortical collecting duct (CD), whereas only mucus-secreting cells are present in the MCDs. The volume flux (Jv) in the MCDs from intact birds and that from the water-deprived birds were nearly zero; after exposure to a hyperosmotic bath and AVT (2 x 10(-5) M), the Jv was significantly higher in water-deprived birds. The diffusional water permeability (Pdw) was moderately high in MCDs bathed in an isosmotic bath in which the Pdw was increased slightly by AVT (10(-5) M, bath) and more markedly (10(-5) M) by forskolin (Fsk), whereas 1,9-dideoxy Fsk (an inactive analogue) showed no effect. Furthermore, the basal adenosine 3',5'-cyclic monophosphate (cAMP) levels were higher in the medulla than in the cortex and were stimulated only slightly by AVT (10(-5) M) and markedly by Fsk (10(-4) M) in both the cortex and medulla. These results in the C. coturnix CD indicate the following. 1) Two types of cells are present; whereas dark cells resemble mammalian intercalated cells morphologically, it is not certain whether mucus-secreting cells are equivalent to principal cells. 2) AVT increases Pdw via a cAMP mechanism; the relatively high basal Pdw and minor effect of AVT on Jv and Pdw suggest, however, that diffusional water movement across the MCD may occur without significant direct control by AVT.
Cellular immunity is not compromised by high serum corticosterone concentrations in prairie voles
Authors: Klein S. L. , Taymans S. E. , DeVries A. C. , Nelson R. J.
Published: December 2017

Glucocorticoids compromise immune function in glucocorticoid-sensitive species (e.g., mice), but these immunosuppressive effects may be reduced in glucocorticoid-resistant species. Prairie voles (microtus ochrogaster) have been characterized as glucocorticoid-resistant to their high circulating levels of corticosterone. Because glucocorticoid-sensitive species display suppressed lymphocyte proliferation in response to elevated blood glucocorticoid levels, proliferative values were hypothesized to be reduced in house mice (Mus musculus) compared with prairie voles. Prairie voles exhibited significantly higher splenocyte proliferative responses to the T cell mitogen, Concanavalin A, despite having higher basal total and free serum corticosterone levels than mice. Neither total nor free serum corticosterone correlated with proliferative responses from either species. These data provide further evidence for glucocorticoid resistance in prairie voles and suggest that the interactions between the hypothalamic-pituitary-adrenal axis and the immune system in prairie voles may differ from those in mice or other glucocorticoid-sensitive species. Therefore, prairie voles may serve as a valuable animal model for the syndrome of glucocorticoid resistance in humans and the role of glucocorticoids in conditions characterized by a hyperactive immune system.
GABA release in posterior hypothalamus across sleep-wake cycle
Authors: Nitz D. , Siegel J. M.
Published: December 2017

The activity of neurons in the posterior hypothalamus (PH) is thought to contribute to the production of wakefulness and electroencephalograph desynchronization. Inactivation of neuronal activity in this area is known to induce sleep. Most PH neurons decrease unit discharge during slow-wave sleep (SWS) relative to wake and rapid eye movement sleep. In the present study, we sought to examine potential sources of inhibition or disfacilitation underlying the reduction of PH unit activity during SWS in the cat. We employed the microdialysis technique in conjunction with high-performance liquid chromatography methods for the quantification of glutamate, glycine, and gamma-aminobutyric acid (GABA) release. We found a selective increase in GABA release during SWS in the PH. Glutamate and glycine levels were unchanged across the sleep-wake cycle. microinjection of the GABAA-receptor agonist muscimol, into the same areas from which microdialysis samples were collected, increased SWS time. Our studies support the hypothesis that GABA release in the posterior hypothalamus mediates inhibition of posterior hypothalamic neurons, thereby facilitating SWS.
Stimulation of aortic nerve evokes three different response patterns in neurons of rostral VLM of the rat
Authors: Zagon A. , Spyer K. M.
Published: December 2017

Because the aortic nerve of the rat is believed to contain only barosensory fibers in a functionally significant number, stimulation of this nerve provides a convenient means to identify barosensitive neurons in the central nervous system. The aim of the present study was to describe the characteristics of responses to stimulation of the aortic nerve in the neurons of the ventrolateral medulla oblongata (VLM) from in vivo intracellular recordings. Data were obtained from 25 neurons that were either spontaneously active and exhibited pulse-synchronous discharge or were silent. Cells that showed a regular increase in their discharge rate during diastole responded with either an inhibitory postsynaptic potential (IPSP, group 1; n = 3) or a biphasic excitatory postsynaptic potential (EPSP)-IPSP (group 2; n = 10) to aortic nerve stimulation. Parameters of the inhibitory response were similar in both groups (27 +/- 2 and 31 +/- 2 ms for onset latency and 55 +/- 10 and 67 +/- 7 ms in duration, respectively). In group 2 cells, the inhibition was, however, preceded by a brief excitation (14 +/- 2 ms for onset latency and 13 +/- 1 ms in duration). Group 3 neurons, which showed a regular increase in their discharge rate during or before systole (n = 7), responded with an EPSP (20 +/- 2 ms for onset latency and 44 +/- 5 ms in average duration). Group 1 and 3 responses were also encountered in quiescent neurons (n = 5). Intracellular labeling revealed that neurons of all three types were localized within the rostral VLM. The functional significance of these findings is discussed.
Effects of 2-deoxy-D-glucose and insulin on plasma glucose levels and behavioral thermoregulation of toads
Authors: Branco L. G.
Published: December 2017

The present study was designed to test the hypothesis that hypoglycemia induces hypothermia in ectotherms and to elucidate the mechanisms responsible for behavioral hypothermia. Behavioral hypothermia is a stress response that occurs in organisms ranging from protozoans to mammals, but very little is known about the cellular mechanisms involved. Toads equipped with a temperature probe were tested in a thermal gradient (10-40 degrees C). Insulin was used to reduce plasma glucose levels, and an inhibitor of glucose utilization, 2-deoxy-D-glucose (2-DG), was used to cause intracellular glucopenia. Insulin injections into the dorsal lymph sac caused significant reductions of both plasma glucose levels and body temperature. To determine if the response was mediated by extracellular glucose receptors or an intracellular mechanism. 2-DG was also injected into the lymph sac. 2-DG caused a similar drop in body temperature and a marked increase in plasma glucose. To assess the role of central thermoregulatory mechanisms, a smaller dose of 2-DG was injected into the fourth cerebral ventricle or the lymph sac. Intracerebroventricular injection of 2-DG caused a decrease in body temperature despite elevated circulating glucose levels, whereas injection into the lymph sac caused no significant change. The data indicate that exclusion of glucose from central rather than peripheral sites plays a major role in the hypoglycemia-induced behavioral hypothermia and that intracellular mechanisms rather than extracellular glucose receptors are involved in this response. Hypothermia may be a beneficial response to hypoglycemia in toads because it dampens cellular oxidative demands during glucose deprivation.
Use of [3H]methylglucose and [14C]iodoantipyrine to determine kinetic parameters of glucose transport in rat brain
Authors: Mori K. , Maeda M.
Published: December 2017

Local maximal velocities of transport (Tmax) and the half-maximum transport constants (KT) for glucose transport across the blood-brain barrier have been determined in local regions of the brain in normal conscious rats. [14C]iodoantipyrine and [3H]methylglucose were infused together intravenously for 2 min in rats with plasma glucose concentrations maintained at different levels, and the time courses of the tracer levels in arterial blood were measured. Local 14C and 3H concentrations were then measured in tissue samples dissected from the frozen brains. By comparing the transport-limited uptake of [3H]methylglucose with the blood flow-limited uptake of [14C]iodoantipyrine, the value of m, a factor between 0 and 10 that accounts for diffusion and/or transport limitations, was derived, and from the equation, m = 1 - PS/F (where PS is capillary permeability-surface area product and F is cerebral blood flow), the permeability-capillary surface area for methylglucose was calculated (S. S. Kety. Pharmacol. Rev. 3: 1-41, 1951). Values for Tmax and KT for glucose were calculated by application of Michaelis-Menten kinetic relationships adapted for the competition for transport between glucose and methylglucose. Tmax was determined in three representative gray structures and one white structure of the brain: Tmax was 5.3 +/- 0.3 (SD) mumol.g-1.min-1 in the gray structures and 4.3 mumol.g-1.min-1 in the white structure. KT was 3.6 +/- 0.4 (SD) mM in the gray structures and 5.9 mM in the white structure. This approach allows the simultaneous determination of local values of Tmax and KT for glucose and the rates of blood flow in various regions of the brain in conscious animals.
Chronic fetal placental embolization and hypoxemia cause hypertension and myocardial hypertrophy in fetal sheep
Authors: Murotsuki J. , Challis J. R. , Han V. K. , Fraher L. J. , Gagnon R.
Published: December 2017

To examine the cardiovascular effects on the fetus of an elevated umbilical vascular resistance resulting in fetal hypoxemia, we embolized the fetal side of the placenta in pregnant sheep and measured cardiovascular and hormonal changes and cellular growth in fetal heart. Chronically catheterized fetal sheep were embolized (n = 6) for 21 days between 0.74 and 0.88 of gestation into the descending aorta until arterial oxygen content was decreased by 40-50% of the preembolization value. Control animals (n = 6) received saline only. During embolization, fetuses became chronically hypoxemic (P < 0.001) and hypertensive (P < 0.001), with a progressive increase in umbilical artery resistance index (P < 0.001). There was also an increase in fetal plasma norepinephrine throughout the study period (P < 0.05). On day 21 of embolization, fetuses showed asymmetrical growth restriction, increased heart weight (P < 0.01), and increase in right and left ventricular wall thickness (P < 0.05) compared with control animals. The protein-to-DNA ratio, an index of cell size, increased in the right ventricular myocardium in the embolized group (P < 0.001), suggesting myocardial cell hypertrophy. We conclude that, during chronic placental damage leading to fetal hypoxemia with an increase in umbilical artery resistance index, fetuses developed arterial hypertension and asymmetrical growth restriction and that increases in afterload to the heart and plasma norepinephrine likely caused fetal myocardial hypertrophy.
Sexual dysfunction in the diabetic BB/WOR rat: a role of central neuropathy
Authors: McVary K. T. , Rathnau C. H. , McKenna K. E.
Published: December 2017

The pathophysiological mechanisms of diabetic impotence remain obscure. We have presented an analysis of sexual function in a diabetic rat (BB/WOR) model characterized by diffuse neuropathic changes without a confounding vasculopathy that allows us to define the neural components of erectile failure. Copulatory behavioral testing demonstrated that diabetic males were severely impaired: the controls mounted three times more than the diabetics and had about one-half the latency to first mount. The diabetics had about one-fourth the number of intromissions and took nearly twice as long to achieve first ejaculation. The number of ejaculations was drastically reduced as well. We examined sexual reflexes in the anesthetized acutely spinalized rat. These experiments tested the integrity of spinal circuits controlling sexual function. Reflex testing demonstrated that spinal sexual reflexes were also severely impaired: the onset latency of reflexes was more than doubled, and the duration of reflexes was less than one-half. More than one-half of the diabetic rats showed no penile erections. Neural studies showed even more derangement in reflex measures in rats, without erection. Nerve conduction velocity experiments suggested a peripheral neuropathic change in hypogastric nerve and motor pudendal nerve fibers. These dysfunctional findings were seen without any androgen deficiency. These results indicate that diabetic impotence in this model reflects central and peripheral neuropathic disease processes.
Uterine arterial vasoconstrictions mediated by ovarian nerves in virgin and postpartum rats
Authors: Hutchison S. M. , Tietz A. E. , Trostel K. A. , Schramm L. P.
Published: December 2017

In most mammals, including humans, pregnancy results in the loss of most uterine vasomotor fibers. These experiments determined whether, despite this denervation, sympathetic nerves mediated uterine vasoconstrictions in the rat 24 h after delivery. Both virgin and uniparous postpartum rats were anesthetized with urethan. Femoral vessels were cannulated for measurement of arterial pressure and intravenous administration of fluids and drugs. Blood flow was measured in a uterine artery after ligation of all anastomotic ovarian vessels. Electrical stimulation of ovarian nerve efferents elicited frequency-dependent uterine vasoconstrictions in both virgin and postpartum rats. Vasoconstrictions in postpartum rats were not significantly different from those observed in virgins. In both virgin and postpartum rats, neurogenic vasoconstrictions were reduced by combined alpha 1- and alpha 2-adrenergic blockade. We conclude that the uterine branches of the ovarian nerve mediate adrenergic uterine vasoconstrictions. In the largely denervated uterus of the postpartum rat, these vasoconstrictions may be mediated by surviving innervation of the uterine artery and its major branches. Sympathetic vasoconstriction acting at these sites would constitute an effective defense against postpartum hemorrhage.
Purine and pyrimidine nucleotide-sensitive phosphoinositidase C in ampulla from frog semicircular canal
Authors: Butlen D. , Bernard C. , Ammar A. , Ferrary E.
Published: December 2017

A microassay was developed to screen the abilities of ATP analogues to stimulate phosphoinositidase C in single ventral regions (including dark cells and sensory cells) of ampullas microdissected from posterior vertical semicircular canals of Rana ridibundo and labeled with myo-[3H]inositol. ATP induced a dose-dependent and saturable increase of total [3H]linositol phosphate production accompanied by an equivalent decrease in the [3H]phosphoinositide pool. The rank order of analogues revealing agonistic potencies for phosphoinositidase C activation was as follows: uridine 5'-triphosphate > or = adenosine 5'-O-[3-thiophosphate] tetralithium > adenosine 5'-O-[2-thiodiphosphate] trilithium > or = ATP > or = ADP = inosine 5'-triphosphate > or = guanosine 5'-triphosphate > or = 2-methylthio-adenosine 5'-triphosphate tetrasodium > or = 2'-desoxy-thymidine 5'-triphosphate > or = cytidine 5'-triphosphate = (alpha, beta)-methyl ATP > AMP, whereas adenosine 3',5'-cyclic monophosphate and adenosine were almost devoid of activity. For antagonists, 1,4'-diisothiocyanostilbene-2, 2'-disulfonic acid was far more active than suramin for competitive inhibition of ATP-induced enzyme stimulation, whereas reactive blue 2 acted as a noncompetitive inhibitor. Results indicate that the putative P2 receptors triggering phosphoinositidase C activation in ventral ampullary epithelium from frog semicircular canal exhibit mainly the functional properties of P2Y and P2U receptors.
Administration of AVP to the area postrema alters response of NTS neurons to afferent inputs
Authors: Qu L. , Hay M. , Bishop V. S.
Published: December 2017

This study was designed to determine if arginine vasopressin (AVP) facilitates the response of nucleus of the solitary tract (NTS) neurons to baroreceptor input. In anesthetized sinoaortic-denervated vagotomized rabbits, AVP was intravenously infused (15 microg x kg(-1) x min(-1), 1 min) or microinjected into the area postrema (AP; 1 ng/nl, 10 nl). Extracellular recordings of evoked NTS neuronal responses to electrical stimulation of the aortic depressor nerve (ADN) or vagus nerve (1 Hz, 2-20 V, 0.05-0.6 ms) were evaluated before and after AVP administration. In neurons receiving input from the ADN (n = 19), 58% of them increased their responses after AVP (40.3 +/- 5.0 to 71.5 +/- 4,8%, P < 0.001). Similarly, in neurons activated by vagal stimulation (n = 22), 55% of them were facilitated during AVP administration (59.7 +/- 12.8 to 90.8 +/- 10.7%, P < 0.01). This action of AVP was independent of the mode of AVP administration, since either microinjection or venous infusion was effective in augmenting responses of NTS neurons to aortic/vagal stimulation. In an additional 37 spontaneous NTS neurons, AVP showed no effect on the mean baseline firing rate (8.9 +/- 1.3 vs. 9.6 +/- 1.3 spikes/s, P > 0.05), but increased neuronal activity in 54% of neurons (6.9 +/- 1.3 vs. 13.1 +/- 1.7 spikes/s, P < 0.01). In two rabbits pretreated with vasopressin antagonist (15 microg/kg iv), AVP failed to produce facilitatory effects (n = 8). The results of this study provide evidence in support of the hypothesis that circulating peptides modulate the arterial baroreflex via activation of neurons in the AP.
Hemodilution, central blood volume, and renal responses after an isotonic saline infusion in humans
Authors: Johansen L. B. , Bie P. , Warberg J. , Christensen N. J. , Hammerum M. , Videbaek R. , Norsk P.
Published: December 2017

To test the hypothesis that hemodilution is a mediator of the renal responses to an isotonic saline infusion in the supine position, eight males underwent 1) intravenous infusion of 1.5 liter of saline over 21 min (Saline), 2) infusion of 1.5 liter of saline in combination with lower body negative pressure for 3 h (LBNP+Saline) to maintain central blood volume unchanged, and 3) a control study without infusion or LBNP. During the Saline series, central venous pressure (CVP) and left atrial diameter (LAD) increased by 4.4 +/- 0.6 mmHg and 2.6 +/- 0.4 mm (P < 0.05), respectively, whereafter they declined toward preinfusion levels. During LBNP+Saline, CVP and LAD were unchanged. Plasma colloid osmotic pressure remained unchanged during control and showed identical decreases by 5 mmHg (P < 0.05) in the Saline and LBNP+Saline series. During the 3rd h of LBNP, renal sodium excretion (U(Na)V) peaked at 296 +/- 55 micromol/min vs. a higher value of 383 +/- 54 micromol/min (P < 0.05) during Saline. The increase in U(Na)V above that of control during the 3rd h of LBNP+Saline constituted 48% of that during Saline. Plasma renin activity and plasma aldosterone concentration showed similar patterns of decrease after saline infusion irrespective of LBNP, whereas plasma norepinephrine was elevated late in the LBNP period compared with during Saline and control (P < 0.05). It is concluded that the maintenance of a constant CVP and LAD reduces the natriuresis of acute saline loading by about one-half. Thus hemodilution in conjunction with suppression of renin and aldosterone release (independent of change in CVP and LAD) might account for the remaining natriuresis of infusion.
Influence of simulated microgravity on the sympathetic response to exercise
Authors: Woodman C. R. , Kregel K. C. , Tipton C. M.
Published: December 2017

Rats exposed to simulated conditions of microgravity exhibit reductions in aerobic exercise capacity that may be due to an impaired ability of the sympathetic nervous system (SNS) to mediate an increase in cardiac output and to redistribute blood flow. The purpose of this study was to quantify the sympathetic response to exercise in rats after exposure to 14 days of simulated microgravity or control conditions. To achieve this aim, rats were exposed to 14 days of head-down suspension (HDS) or cage control (CC) conditions. On day 14, norepinephrine (NE) synthesis was blocked with alpha-methyl-p-tyrosine, and the rate of NE depletion after synthesis blockade was used to estimate SNS activity in the left ventricle, spleen, and soleus muscle during treadmill exercise at 75% of maximal oxygen uptake. When compared with CC rats, the sympathetic response to exercise in HDS rats was characterized by a lower rate of NE depletion in the left ventricle (-82%) and spleen (-42%). The rate of NE depletion in the soleus muscle was 47% higher. These differences could contribute to the decrement in aerobic capacity of HDS rats by impairing their ability to augment cardiac output and to redirect blood flow to actively contracting skeletal muscle during exercise.
Laryngeal reflex apnea is blunted during and after hindlimb muscle contraction in sheep
Authors: Haouzi P. , Beyaert C. , Gille J. P. , Chalon B. , Marchal F.
Published: December 2017

This study was carried out on seven chloralose-anesthetized sheep and was designed to investigate the role of muscular afferent fiber stimulation on the duration of reflex apnea triggered by laryngeal stimulation (LS). In six animals, injection of distilled water onto the laryngeal mucosa provoked a 15.7 +/- 1.0 s (mean +/- SE) apnea associated with a rise in systemic blood pressure (+7 +/- 0.8 Torr). Electrically induced contractions (EIC) of the hindlimb muscles doubled the metabolic rate and ventilation and reduced the duration of the apnea produced by LS to 7.4 +/- 1.0 s (P < 0.01). Apnea duration was still reduced during the first minute after the cessation of EIC (7.2 +/- 1.1 s, P < 0.01) but returned to control after a 5-min recovery period (16.7 +/- 1.6 s). The apnea triggered by LS was also reduced during EIC when the venous return was impeded by occluding the inferior vena cava (5.2 +/- 1.1 s, P < 0.01), despite a profound hypocapnia (20.7 +/- 0.3 Torr). The duration of apnea was not significantly affected (14.2 +/- 1.4 s) by breathing a 6% CO2-14% O2 in N2 gas mixture that roughly mimicked the alveolar gas composition when the apnea turned off. These results suggest that chemical drive has a negligible role in the fast reinitiation of breathing after LS during muscular stimulation. Stimulation of muscle afferent fibers does, however, appear to be a potent source of ventilatory reflexes capable of counteracting the inhibition of breathing resulting from laryngeal stimulation. Conversely, it is postulated that any reduction in somatic afferent traffic during this type of reflex apnea, including that resulting from the LS-induced systemic vasoconstriction, may delay the termination of apnea.
Fever suppression by subdiaphragmatic vagotomy in guinea pigs depends on the route of pyrogen administration
Authors: Goldbach J. M. , Roth J. , Zeisberger E.
Published: December 2017

It has recently been shown that subdiaphragmatic vagotomy blocks some of the effects of inflammatory stimuli on brain-controlled functions. Therefore, vagal afferent fibers have been proposed to play a prominent role in the communication pathways between the immune system and the brain. In the present study, we investigated the effect of subdiaphragmatic vagotomy on fever induced by intraperitoneal or intramuscular injection of lipopolysaccharide (LPS) or muramyl dipeptide (MDP), which are both cytokine-inducing agents in guinea pigs. Intraperitoneal and intramuscular injections of LPS or MDP were tested in the same animal with an interval of 1 wk. In one experiment, intraperitoneal injections of LPS or MDP were performed at the beginning, followed by intramuscular injections 1 wk later. In another experiment, intramuscular injections of LPS or MDP were performed at the beginning, followed by intraperitoneal injections 1 wk later. The febrile response to intraperitoneal injection of LPS was almost completely abrogated in vagotomized animals compared with sham-operated controls (from 30-330 min after intraperitoneal injection of LPS). The suppression of LPS fever was quantitatively the same in both experiments. In contrast, the response to intramuscular injection of LPS was the same in vagotomized and sham-operated guinea pigs in each of the experiments. Fever induced by intraperitoneal injection of MDP was partly attenuated by subdiaphragmatic vagotomy (between 150 and 300 min after intraperitoneal injection of MDP) in both experiments. Again, the febrile response to intramuscular injections of MDP was not significantly altered by subdiaphragmatic vagotomy. In conclusion, the suppressive effect of subdiaphragmatic vagotomy on fever induced by peripheral immune stimuli depends on the route of pyrogen administration. Because the febrile response to intraperitoneal injection of bacterial pyrogens is strongly diminished in vagotomized guinea pigs, it is suggested that vagal afferent fibers play a crucial role in the transduction of immune signals from the abdominal cavity to the brain.