bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold defense mechanisms in vagotomized rats
Authors: Romanovsky A. A. , Kulchitsky V. A. , Simons C. T. , Sugimoto N. , Szekely M.
Published: December 2017

Subdiaphragmatically vagotomized rats cannot mount a febrile response to pyrogens and are believed to have severe thermoregulatory deficiencies. We addressed the issue of thermoeffector competence of vagotomized rats by asking three questions. In Expt. 1 we asked, can vagotomized rats readily recruit tail skin vasoconstriction in the course of a moderate cold exposure? In Expt. 2 the question was, can brown adipose tissue (BAT) thermogenesis readily be activated in vagotomized rats (e.g., in response to a tail pinch)? In Expt. 3, we investigated the question: can vagotomized rats elevate their body temperature in response to ephedrine (a drug of high hyperthermizing potential) to the same extent as sham-operated controls? Rats were vagotomized or sham operated and implanted with a catheter into the jugular vein and a thermocouple into the interscapular BAT. To prevent the common complications of vagotomy, special perioperative care was given. During experiments, colonic, tail skin, and BAT temperatures (Tc, Tsk, and TBAT, respectively) were measured. The vagotomized animals were well nourished and had a body mass (325 +/- 6 g) similar to that of the controls (338 +/- 6 g). In Expt. 1, in response to external cooling (15 degrees C, 1 h), the vagotomized (n = 30) and sham-operated (n = 31) rats recruited tail skin vasoconstriction at close values of both Tc (37.84 +/- 0.08 and 37.97 +/- 0.07 degrees C) and Tsk (33.16 +/- 0.17 and 33.18 +/- 0.18 degrees C, respectively). In Expt. 2, tail pinch-associated stress in vagotomized rats resulted in a sharp rise in the TBAT-Tc gradient by 0.3-1.0 degree C. In Expt. 3, ephedrine administered intravenously (whether in a 5 or 35 mg/kg dose) evoked similar hyperthermic responses in the vagotomized and sham-operated rats: a moderate (approximately 2.5 degrees C) Tc rise in the low dose and a "supramaximal" (approximately 5.0 degrees C) rise in the high dose. In sum, the answer to all three questions asked is yes. Vagotomized rats, at least when well nourished, exhibit no signs of thermoeffector deficiency. It is, therefore, not effector incompetence but rather vagal deafferentation per se that can explain the febrile irresponsiveness of vagotomized rats.
Trigeminal and chemoreceptor contributions to bradycardia during voluntary dives in rats
Authors: McCulloch P. F. , Ollenberger G. P. , Bekar L. K. , West N. H.
Published: December 2017

This study investigates the importance of chemoreceptive and trigeminal information during voluntarily initiated diving in rats. The heart rate responses to simulated diving are unaffected by chemoreceptor drive [McCulloch, P.F., and N. H. West. Am. J. Physiol. 263 (Regulatory Integrative Comp. Physiol. 32): R1049-R1056, 1992] but are reversibly eliminated by infusion of glutamate receptor antagonists into the spinal trigeminal nuclei [McCulloch, P. F., I. A. Paterson, and N. H. West. Am. J. Physiol. 269 (Regulatory Integrative Comp. Physiol. 38): R669-R677, 1995]. To investigate the role of chemoreceptor drive in conscious dives, rats were made hypercapnic, hyperoxic, or hypoxic predive. The role of trigeminal input was explored by infusing the glutamatergic antagonists D-2-amino-7-phosphoheptanoic acid and 6,7-dinitroquinoxaline-2,3-dione into the region of the trigeminal nuclei. The alteration of arterial blood gases predive had no effect on diving bradycardia. Trigeminal blockade reduced the intensity of the bradycardia but did not abolish it. Chemoreceptor input does not play a significant role in determining heart rate during conscious diving in rats. The attenuation, rather than abolition, of bradycardia on trigeminal blockade suggests either that we achieved incomplete blockade or that an additional spectrum of sensory inputs not present in simulated diving is important in determining the underwater heart rate during conscious diving in rats.
Selective brain cooling: role of angularis oculi vein and nasal thermoreception
Authors: Maloney S. K. , Mitchell G.
Published: December 2017

We have measured blood flows in the angularis oculi (AOV), facial, and jugular veins and temperatures in the carotid artery and near the hypothalamus in three lightly anesthetized sheep while body and nasal mucosal (Tnm) temperatures were varied independently. Above a threshold hypothalamic temperature (Thyp) of 39 degrees C both selective brain cooling (SBC) and AOV blood flow increased. For a given Thyp, the increase in AOV flow and SBC was inversely proportional to Tnm: low Tnm resulted in high AOV flow and SBC, whereas increasing Tnm attenuated both AOV flow and SBC. This decrease in AOV flow results in submaximal SBC, which does not concur with the hypothesis that SBC functions to protect a thermally vulnerable brain. The trigger for these changes in AOV blood flow was Tnm. Occlusion of the AOV during SBC showed that AOV flow accounted for over 80% of SBC. We conclude that SBC is not only a mechanism for reducing brain temperature but may also be a means of adjusting Thyp to facilitate the appropriate thermoregulatory responses.
Attenuation of lipopolysaccharide fever in rats by protein kinase C inhibitors
Authors: Kozak W. , Klir J. J. , Conn C. A. , Kluger M. J.
Published: December 2017

The purpose of this study was to assess the effects of inhibitors of protein kinase C (PKC) on lipopolysaccharide (LPS)-induced fever and changes in circulating interleukin-6 (IL-6) levels in freely moving biotelemetered rats. We used PKC inhibitors with different inhibition constants (Ki): H-7 (Ki = 6 microM) and chelerythrine (Chel; Ki = 0.66 microM; a more potent PKC inhibitor). Rats were injected subcutaneously with either 3 or 15 microM/kg of these inhibitors and then 1 h later were injected intraperitoneally with LPS (50 micrograms/kg). Blood samples for IL-6 bioassay were collected 4 h after LPS injection. H-7 at lower doses did not significantly affect fever and LPS-induced elevation of circulating IL-6, whereas at a higher dose (15 microM/kg) H-7 reduced both fever and the increase of IL-6 (analysis of variance, Scheffe's test, P < 0.05). Chel (3 and 15 microM/kg) significantly reduced fever and almost completely inhibited the LPS-induced elevation of plasma IL-6. In separate experiments, we studied the effect of H-7 on antipyresis due to dexamethasone (Dex). Dex at a dose of 0.6 microM/kg given subcutaneously 1 h before LPS partially prevented fever (approximately 55% inhibition) and attenuated the increase of IL-6 (P < 0.05). Simultaneous pretreatment of the rats with Dex and H-7 (3 microM/kg; a dose that did not affect fever and IL-6 elevation) led to a potentiation of the antipyretic effect of Dex, resulting in no fever. H-7 did not potentiate, however, the inhibitory effect of Dex on LPS-induced elevation of circulating IL-6. We conclude that PKC is involved in the regulation of LPS fever and constitutes a rate-limiting factor in modulation of the fever by glucocorticoids.
A putative growth-related renal Na(+)-Pi cotransporter
Authors: Silverstein D. M. , Barac-Nieto M. , Murer H. , Spitzer A.
Published: December 2017

The mRNA that encodes for NaPi-2, the renal Na(+)-Pi cotransporter that is upregulated by Pi depletion in the adult rat, is low in the young animal. Yet, renal Na-Pi cotransport rates are higher in rapidly growing than in fully grown rats. The aim of this study was to unravel the molecular basis of this apparent discrepancy. Poly(A) RNA obtained from the renal cortex of young animals induced higher rates of Na(+)-Pi cotransport in oocytes than equal amounts of poly(A) mRNA obtained from the renal cortex of mature rats. Moreover, poly(A) RNA obtained from renal cortex of rapidly growing animals treated with antisense NaPi-2 oligomers or depleted of NaPi-2 transcripts by subtractive hybridization with cDNA generated from the renal cortex of adult rats retained its ability to induce Na(+)-Pi cotransport in oocytes. In addition, renal poly(A) RNA of the young subjected to subtraction hybridization generated a 379-base pair reverse transcriptase-polymerase chain reaction product common to all known type II Na(+)-Pi cotransporters. These observations permit us to surmise that the high rates of Na(+)-Pi cotransport prevailing during growth are due, at least in part, to the expression of a specific mRNA that is only partially homologous to that of NaPi-2.
Simultaneous 31P MRS of the soleus and gastrocnemius in Sherpas during graded calf muscle exercise
Authors: Allen P. S. , Matheson G. O. , Zhu G. , Gheorgiu D. , Dunlop R. S. , Falconer T. , Stanley C. , Hochachka P. W.
Published: December 2017

The observation that the amount of lactate formed during hypobaric hypoxia decreases with the severity of hypoxia has become known as the "lactate paradox." We used noninvasive 31P magnetic resonance spectroscopy (MRS) to further probe this problem and explore the nature of muscle metabolism during rest-exercise-recovery transitions in Sherpas indigenous to the high Himalayas of Nepal. MRS data were obtained using a whole body 1-m bore, 1.5-T Phillips Gyroscan spectrometer. Muscle-specific localization of MRS data acquisition was achieved by means of a modified image-selected in vivo spectroscopy sequence (ISIS). The spectra acquired from the medial and lateral gastrocnemius muscle, rich in fast-twitch fibers, were well constrained by selective excitation and by the boundary of the leg. The spectra from a third region contained signals predominantly from the soleus, a muscle formed mainly of slow-twitch fibers. We quantified relative concentration changes in phosphocreatine (PCr), Pi, and ATP during a series of calf muscle work bouts; free ADP concentrations were calculated on the assumption that the creatine phosphokinase reaction was always essentially at equilibrium. Hydrogen ion concentrations were calculated from the chemical shift of Pi, which represents the equilibrium between mono- and diprotonated phosphate. Plantar flexion was quantified using a calf muscle ergometer designed for operation within a 1-m whole body magnet. We found that the concentration of ATP was rigorously regulated and thus did not change despite large changes in ATP turnover rates required through exercise. The relative concentrations of PCr and Pi were linear functions of the percent maximum work rate of the lateral and medial gastrocnemius, but on transition to exercise the fractional concentration changes in these metabolites were much less than the fractional change in muscle ATP turnover rates. The relationship between muscle ATP turnover rate and free ADP concentration was complex; again, a kinetic order of 1 was not observed. In contrast to the gastrocnemius, the soleus muscle sustained much smaller changes in the concentrations of these crucial metabolites during rest-work-recovery transitions. Unlike the situation in most other muscles rich in fast-twitch fibers characterized by lactate-associated acidosis during muscle work, the intracellular pH in gastrocnemius of Sherpas was stable through these protocols, which is consistent with the low lactate production (i.e., with the lactate paradox) observed in indigenous highlanders.
Adrenomedullin in experimental congestive heart failure: cardiorenal activation
Authors: Jougasaki Michihisa , Stevens Tracy L. , Borgeson Daniel D. , Luchner Andreas , Redfield Margaret M. , Burnett John C.
Published: December 2017

Adrenomedullin (ADM) is a new member of a family of vasodilating and natriuretic peptides that plays an important role in cardiorenal regulation. This study was designed to establish the plasma, urinary, cardiac, and renal tissue concentrations and immunohistochemical localizations of ADM in normal dogs and dogs with experimental congestive heart failure (CHF) produced by rapid ventricular pacing. Plasma ADM concentration was 5.6 ± 0.4 pg/ml in normal dogs and significantly increased to 14.5 ± 2.5 pg/ml in CHF dogs ( P < 0.05). Ventricular and renal tissue ADM were significantly increased in CHF dogs compared with normals. Immunohistochemical examination revealed positive ADM immunostaining within the myocytes, and ventricular ADM immunoreactivity was significantly more intense in CHF dogs than in normals. ADM immunoreactivity was also observed in the glomerulus, distal tubules, and medullary collecting duct cells in the kidney, and the intensities of ADM immunoreactivity in these sites were increased in CHF dogs compared with normals. In addition, ventricular ADM was a powerful marker for left ventricular mass, and circulating ADM correlated positively with left ventricular end-diastolic pressure and inversely with cardiac output and ejection fraction. Despite an increase in renal tissue ADM, urinary ADM did not increase in CHF dogs. The current study demonstrates that plasma concentration of ADM is increased in experimental CHF and that ventricular and renal ADM is activated in the progression of CHF. Tissue and circulating ADM also are markers for the alterations in myocardial structure and function. This study supports a potential role for ADM in the neurohumoral activation in experimental CHF.
Gastric branch vagotomy and gastric emptying during and after intragastric infusion of glucose
Authors: Kaplan Joel M. , Siemers William H. , Smedh Ulrika , Schwartz Gary J. , Grill Harvey J.
Published: December 2017

The effect of gastric branch vagotomy (GVX) on the gastric emptying of glucose was evaluated during two phases of emptying control: as the stomach fills and in the postload period. GVX and control rats received a series of intragastric glucose infusions (1.0 ml/min) through indwelling gastric fistulas. In experiment 1, gastric samples were withdrawn either immediately after the offset of 9- or 18-min infusions of 12.5% glucose or at various times up to 36 min postinfusion. In experiment 2, samples were withdrawn either immediately or 30 min after termination of 12-min infusions of 12.5 or 25% glucose. After gastric fill, glucose solute emptying rate was stable over time, not influenced by concentration doubling, and, surprisingly, not affected by GVX. During gastric fill, solute emptying rate doubled with concentration in both GVX and control rats. For each concentration, however, glucose emptied during fill at almost twice the rate in GVX compared with control rats. This accelerated emptying of glucose during fill in GVX rats is consistent with a gastric vagal contribution to inhibitory mechanisms (e.g., receptive relaxation) that operate as the stomach fills under normal conditions. The absence of a GVX effect on emptying after fill suggests either that gastric branch vagal efferents play little role in feedback inhibitory control of glucose emptying under normal conditions or that other systems compensate for the function previously served by vagal gastric branch efferents. Further work is required to address the possible role of the gastric vagus in feedback control of gastric emptying when nutritive fluids other than glucose are delivered.
Rapid photoperiod-induced increase in detectable GnRH mRNA-containing cells in Siberian hamster
Authors: Porkka-Heiskanen Tarja , Khoshaba Naherin , Scarbrough Kathryn , Urban Janice H. , Vitaterna Martha H. , Levine Jon E. , Turek Fred W. , Horton Teresa H.
Published: December 2017

To determine whether changes in gonadotropin-releasing hormone (GnRH) neurons are early indicators of photostimulation, Siberian hamsters were placed in short days (6:18-h light-dark) at 3 ( experiment 1) or 6 ( experiment 2) wk of age where they were held for 3 ( experiment 1) or 4 ( experiment 2) wk. Hamsters were then moved to long photoperiod (16:8-h light-dark). In experiment 1, brains were collected 1–21 days after transfer from short to long days. In experiment 2, brains were collected only on the second morning of long day exposure. Long and short day controls were included in both experiments. Cells containing GnRH mRNA, as visualized by in situ hybridization, were counted. As expected, there were no differences in the number of detectable GnRH mRNA-containing cells among animals chronically exposed to long or short photoperiods. However, on the second morning after transfer from short to long photoperiod, a positive shift in the distribution of GnRH mRNA-containing cells occurred relative to the respective controls in the two experiments. Increases in follicle-stimulating hormone secretion and gonadal growth occurred days later. In conclusion, a rapid but transient increase in the distribution of detectable GnRH mRNA-containing cells is an early step in the photostimulation of the hypothalamic-pituitary-gonadal axis.
Postganglionic sympathetic neurons express endothelin
Authors: Damon Deborah H.
Published: December 2017

Endothelin (ET) is a peptide originally identified as an endothelial-derived vasoconstrictor. It is now recognized that ET is produced by and acts on many other tissues including the brain and spinal cord, where it is believed to modulate neurotransmission. The present studies demonstrate that ET is synthesized by and secreted from postganglionic sympathetic neurons. With the use of Northern analysis, ET-1 mRNA was detected in cultures of sympathetic superior cervical ganglion (SCG) neurons isolated from 3- to 5-day old rat pups. ET-1 and ET-3 peptides were also detected in cultured SCG neurons using immunohistochemistry. ET-1 (50 pg/106 cells) and ET-3 (173 pg/106 cells) were detected by radioimmunoassay of media conditioned by cultured SCG. ET-1 (77 pg/mg protein) and ET-3 (30 pg/mg protein) were also detected by radioimmunoassay of extracts of adult SCG.
Activation of the NPY Y5 receptor regulates both feeding and energy expenditure
Authors: Hwa Joyce J. , Witten Melanie B. , Williams Patricia , Ghibaudi Lorraine , Gao Jun , Salisbury Brian G. , Mullins Deborra , Hamud Fozia , Strader Catherine D. , Parker Eric M.
Published: December 2017

Intracerebroventricular (ICV) administration of neuropeptide Y (NPY) has been shown to decrease energy expenditure, induce hypothermia, and stimulate food intake. Recent evidence has suggested that the Y5 receptor may be a significant mediator of NPY-stimulated feeding. The present study attempts to further characterize the role of NPY Y5-receptor subtypes in feeding and energy expenditure regulation. Satiated Long-Evans rats with temperature transponders implanted in the interscapular brown adipose tissue (BAT) displayed a dose-dependent decrease in BAT temperature and an increase in food intake after ICV infusion of NPY. Similar effects were induced by ICV administration of peptide analogs of NPY that activate the Y5 receptor, but not by analogs that activate Y1, Y2, or Y4 receptors. Furthermore, ICV infusion of the Y5 selective agonistd-[Trp32]-NPY significantly reduced oxygen consumption and energy expenditure of rats as measured by indirect calorimetry. These data suggest that the NPY Y5-receptor subtype not only mediates the feeding response of NPY but also contributes to brown fat temperature and energy expenditure regulation.
Intermittent bright light and exercise to entrain human circadian rhythms to night work
Authors: Baehr Erin K. , Fogg Louis F. , Eastman Charmane I.
Published: December 2017

Bright light can phase shift human circadian rhythms, and recent studies have suggested that exercise can also produce phase shifts in humans. However, few studies have examined the phase-shifting effects of intermittent bright light, exercise, or the combination. This simulated night work field study included eight consecutive night shifts followed by daytime sleep/dark periods (delayed 9 h from baseline). There were 33 subjects in a 2 × 2 design that compared 1) intermittent bright light (6 pulses, 40-min long each, at 5,000 lx) versus dim light and 2) intermittent exercise (6 bouts, 15-min long each, at 50–60% of maximum heart rate) versus no exercise. Bright light and exercise occurred during the first 6 h of the first three night shifts. The circadian phase marker was the demasked rectal temperature minimum. Intermittent bright-light groups had significantly larger phase delays than dim-light groups, and 94% of subjects who received bright light had phase shifts large enough for the temperature minimum to reach daytime sleep. Exercise did not affect phase shifts; neither facilitating nor inhibiting phase shifts produced by bright light.
Flow reduces the amplitude and increases the frequency of lymphatic vasomotion: role of endothelial prostanoids
Authors: Koller Akos , Mizuno Risuke , Kaley Gabor
Published: December 2017

Fluid dynamic forces have substantial effects on the movement of lymph and activity of lymph vessels. The effect of increases in intraluminal flow on spontaneous pumping activity of isolated collecting lymphatics has not yet been characterized in a condition in which the intraluminal pressure is constant. Thus, in afferent lymph microvessels isolated from rat iliac lymph nodes, changes in maximum (Dmax) and minimum (Dmin) diameter to increases in perfusate flow were investigated in the presence of a constant perfusion pressure of 6 cmH2O. Intraluminal flow was elicited by increases in the difference between outflow and inflow pressures (Pdiff, from 0 to 6 cmH2O). Diameters were measured by videomicroscopy. In response to increases in perfusate flow, Dmax and Dmin of lymphatics decreased from 157.5 ± 6.1 to 90.9 ± 5.6 μm and from 91.9 ± 5.3 to 66.3 ± 3.6 μm, respectively, whereas vasomotion frequency increased from 18.0 ± 0.7 min−1 to 23.4 ± 1.1 min−1 (at Pdiff of 4 cmH2O). Removal of extracellular Ca2+ abolished spontaneous diameter oscillations; under these conditions the passive diameter of lymphatics was 216.0 ± 7.1 μm and did not change in response to increases in perfusion. In the absence of endothelium, flow-induced changes in Dmax, Dmin, and oscillation frequency were eliminated. N ω-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase, did not affect flow-induced changes in diameter of lymphatics. In contrast, indomethacin, an inhibitor of prostaglandin synthesis, or SQ-29,548, a PGH2/thromboxane A2(PGH2/TxA2) receptor blocker, inhibited the perfusion-induced reduction of Dmax and Dmin of lymphatics and also the increase in the frequency of vasomotion. These findings suggest that the sensitivity of lymphatic endothelium to increases in intraluminal flow could provide an important local intrinsic mechanism for the control of lymphatic resistance by release of constrictor prostanoids PGH2/TxA2.
Effect of cardiac receptor stimulation on renal vascular resistance in the pregnant rat
Authors: Hines Tina , Herzer William A.
Published: December 2017

Stimulation of cardiac receptors (CR) evokes blunted reflex reductions in mean arterial pressure (MAP) in pregnant compared with virgin rats. Because CR-mediated sympathoinhibition has preferential effects on the kidney, we tested whether, during pregnancy, renal vascular resistance (RVR) changes less in response to CR stimulation and investigated possible mechanisms. MAP, right atrial pressure, renal sympathetic nerve activity (RSNA), renal blood flow (RBF), and RVR were measured in anesthetized animals in response to CR stimulation by graded atrial injections of saline. Baseline MAP and RVR and reflex changes in these variables during CR stimulation were reduced in late-pregnant vs. virgin rats ( P< 0.05). Reflex changes in RSNA were attenuated in pregnant rats, but changes in RBF as a function of RSNA were similar in both groups. ANG II AT1-receptor blockade increased basal RBF more in virgin rats ( P < 0.05), but between-group differences in reflex changes in MAP, RSNA, and RVR were maintained after AT1blockade. Thus during CR simulation, reflex changes in RVR were reduced in pregnant versus virgin rats. This difference does not appear to involve differential effects of ANG II.
Bright light during lactation alters the functioning of the circadian system of adult rats
Authors: Canal-Corretger M. M. , Cambras T. , Vilaplana J. , Díez-Noguera A.
Published: December 2017

To examine the role of light in the maturation of the circadian pacemaker, twelve groups of rats were raised in different conditions of exposure to constant bright light (LL) during lactation: both duration and timing of LL were varied. We studied the motor activity rhythm of the rats after weaning, first under LL and then under constant darkness (DD). In DD, two light pulses [at circadian time 15 (CT15) and CT22] were applied to test the response of the pacemaker. Greater exposure to LL days during lactation increased the number of rhythmic animals and the amplitude of their motor activity rhythm in the LL stage and decreased the phase delay due to the light pulse at CT15. The timing of LL during lactation affected these variables too. Because the response of the adult to light depended on both the number and timing of LL days during lactation, the exposure to light at early stages may influence the development of the circadian system by modifying it structurally or functionally.
Influence of angiotensin on the early progression of heart failure
Authors: Lohmeier Thomas E. , Mizelle H. Leland , Reinhart Glenn A. , Montani Jean-Pierre
Published: December 2017

The purpose of this study was to elucidate the role of circulating ANG II in mediating changes in systemic and renal hemodynamics, salt and water balance, and neurohormonal activation during the early progression of heart failure. This objective was achieved by subjecting six dogs to 14 days of rapid ventricular pacing (240 beats/min) while fixing plasma ANG II concentration (by infusion of captopril + ANG II) either at approximately normal ( days 1–8, 13–14) or at high physiological ( days 9–12) levels. Salt and water retention occurred during the initial days of pacing before sodium and fluid balance was achieved by day 8. At this time, cardiac output and mean arterial pressure were reduced to ∼55 and 75% of control, respectively; compared with cardiac output, reductions in renal blood flow were less pronounced. Although plasma ANG II concentration was maintained at approximately normal levels, there were sustained elevations in total peripheral resistance (to ∼135% of control), filtration fraction (to ∼118% of control), and plasma norepinephrine concentration (to 2–3 times control). During the subsequent high rate of ANG II infusion on days 9–12, there were no additional sustained long-term changes in either systemic or renal hemodynamics other than a further rise in right atrial pressure. However, high plasma levels of ANG II induced sustained antinatriuretic, sympathoexcitatory, and dipsogenic responses. Because these same long-term changes occur in association with activation of the renin-angiotensin system during the natural evolution of this disease, these results suggest that increased plasma levels of ANG II play a critical role in the spontaneous transition from compensated to decompensated heart failure.
Chronic infusion of norepinephrine into the VMH of normal rats induces the obese glucose-intolerant state
Authors: Cincotta Anthony H. , Luo Shuqin , Zhang Ying , Liang Yin , Bina Keshavan G. , Jetton Thomas L. , Scislowski Piotr W. D.
Published: December 2017

Increases in ventromedial hypothalamic (VMH) norepinephrine (NE) levels and/or activities have been observed in a variety of animal models of the obese insulin-resistant condition. This study examined the metabolic effects of chronic NE infusion (25 nmol/h) into the unilateral VMH of normal rats. Within 4 days, VMH NE infusion significantly increased plasma insulin (140%), glucagon (45%), leptin (300%), triglyceride (100%), abdominal fat pad weight (50%), and white adipocyte lipogenic (100%) and lipolytic (100%) activities relative to vehicle-infused rats. Furthermore, isolated islet insulin secretory response to glucose (15 mM) within 4 days of such treatment was increased over twofold ( P < 0.05). Among treated animals, fat stores continued to increase over time and plateaued at ∼2 wk (3-fold increase), remaining elevated to the end of the study (5 wk). By week 4 of treatment, NE infusion induced glucose intolerance as evidenced by a 32% increase in plasma glucose total area under the glucose tolerance test curve ( P< 0.01). Whole body fat oxidation rate measured after 5 wk of infusion was significantly increased among treated animals as evidenced by a reduced respiratory quotient (0.87 ± 0.01) relative to controls (0.90 ± 0.01). VMH NE infusion induced hyperphagia (30%) only during the first week and did not affect body weight over the 5-wk period. Increases in VMH NE activity that are common among obese insulin-resistant animal models can cause the development of this obese glucose-intolerant (metabolic) syndrome.
Alterations in spinal cord Fos protein expression induced by bladder stimulation following cystitis
Authors: Vizzard Margaret A.
Published: December 2017

These studies examined Fos protein expression in spinal cord neurons synaptically activated by stimulation of bladder afferent pathways after cyclophosphamide (CYP)-induced bladder inflammation. In urethan-anesthetized Wistar rats with cystitis, intravesical saline distension significantly ( P ≤ 0.0005) increased the number of Fos-immunoreactive (IR) cells observed in the rostral lumbar (L1, 35 cells/section; L2, 27 cells/section) and caudal lumbosacral (L6, 120 cells/section; S1, 96 cells/section) spinal cord compared with control animals, but Fos protein expression in the L5 segment was not altered. The topographical distribution of Fos-IR cells was also altered in the lumbosacral spinal cord. The majority of Fos-IR cells were distributed in the dorsal commissure (45%), with smaller percentages in the sacral parasympathetic nucleus (25%), medial dorsal horn (20%), and lateral dorsal horn (10%). These results demonstrate that urinary bladder distension produces increased numbers and an altered distribution pattern of Fos-IR cells after cystitis. This altered distribution pattern resembles that following noxious irritation of the bladder in control animals. Pretreatment with capsaicin significantly reduced the number of Fos-IR cells induced by bladder distension after cystitis. These data suggest that chronic cystitis can reveal a nociceptive Fos expression pattern in the spinal cord in response to a non-noxious bladder stimulus that is partially mediated by capasaicin-sensitive bladder afferents.
Effect of maternal undernutrition in early gestation on ovine fetal blood pressure and cardiovascular reflexes
Authors: Hawkins Paul , Steyn Clare , Ozaki Takashi , Saito Tsukuru , Noakes David E. , Hanson Mark A.
Published: December 2017

Human epidemiological and animal experimental studies suggest that maternal undernutrition during pregnancy may alter cardiovascular development of the offspring. The extent to which these effects involve changes in fetal cardiovascular function and whether they are necessarily linked to reduced fetal growth is unknown. In sheep, we investigated the effect of a 15% reduction in maternal global nutrition for the first 70 days of gestation (term = 147 days) on fetal blood pressure development, baroreflex control of fetal heart rate (FHR), and cardiovascular responses to acute hypoxemia in late gestation. Basal mean arterial pressure ( P < 0.05), systolic blood pressure ( P < 0.05), diastolic blood pressure ( P < 0.05), and rate-pressure product ( P < 0.001) were significantly lower in fetuses of nutritionally restricted ewes (R) compared with controls (C). FHR was not altered. The operating point for the fetal baroreflex was significantly lower in R fetuses compared with C ( P < 0.01), but there was no difference between the groups in the cardiovascular response to hypoxemia. We conclude that mild maternal undernutrition alters fetal cardiovascular development, producing low blood pressure and resetting of baroreflex control mechanisms. This effect occurs without any changes in fetal growth or blood gas status.
Sympathoexcitatory CVLM neurons mediate responses to caudal pressor area stimulation
Authors: Natarajan Madhusudan , Morrison Shaun F.
Published: December 2017

Neurons in the caudal pressor area (CPA) are a source of tonic sympathoexcitation that is dependent on activation of cardiovascular sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM). In the present study, we sought to clarify the mechanism through which CPA neurons elicit increases in RVLM neuronal discharge, vasoconstrictor sympathetic tone, and arterial pressure. In urethan-chloralose-anesthetized, paralyzed, and artificially ventilated rats, bilateral disinhibition of CPA with bicuculline (Bic) after bilateral disinhibition of caudal ventrolateral medulla (CVLM) caused increases in splanchnic sympathetic nerve activity (+277% control) and arterial pressure (+54 mmHg). Inhibition of CVLM neurons with muscimol abolished the pressor response to activation of CPA neurons, suggesting that neurons within CVLM mediate the excitatory responses from CPA. Disinhibition of CVLM and CPA with Bic enhanced the sympathoexcitatory responses to stimulation of CPA with dl-homocysteic acid, which were blocked by microinjections of kynurenic acid into CVLM. We conclude that the pathway from CPA to RVLM involves an obligatory glutamatergic activation of sympathoexcitatory neurons in the vicinity of CVLM.
Head-down bed rest alters sympathetic and cardiovascular responses to mental stress
Authors: Kamiya Atsunori , Iwase Satoshi , Michikami Daisaku , Fu Qi , Mano Tadaaki
Published: December 2017

Astronauts usually work under much mental stress. However, it is unclear how and whether or not an exposure to microgravity affects physiological response to mental stress in humans. To examine effects of microgravity on vasomotor sympathetic and peripheral vasodilator responses to mental stress, we performed 10 min of mental arithmetic (MA) before and after 14 days of 6° head-down bed rest (HDBR), a ground-based simulation of spaceflight. Total muscle sympathetic nerve activity (MSNA, measured by microneurography) slightly increased during MA before HDBR, and this increase was augmented after HDBR. Calf blood flow (measured by venous occlusion plethysmography) increased and calf vascular resistance (calculated by dividing mean blood pressure by calf blood flow) decreased during MA before HDBR, but these responses were abolished after HDBR. Increases in heart rate and mean blood pressure during MA were not different between before and after HDBR. These findings suggest that HDBR augmented vasomotor sympathoexcitation but attenuated vasodilatation in the calf muscle in response to mental stress.
Roles of Ca2+ and PKC in regulation of acid/base transport in isolated proximal tubules
Authors: Yamada H. , Seki G. , Taniguchi S. , Uwatoko S. , Nosaka K. , Suzuki K. , Kurokawa K.
Published: December 2017

Roles of Ca2+ and protein kinase C (PKC) in the regulation of acid/base transport in isolated rabbit proximal tubules were investigated by measuring cytosolic Ca2+ concentrations ([Ca2+]i) and cell pH (pHi) with fluorescent probes. Ionomycin (0.2 microM) increased [Ca2+]i by approximately 200 nM but did not affect the basolateral Na(+)-HCO3- cotransporter. However, the apical Na+/H+ exchanger was inhibited by 50% by ionomycin, and this inhibition was abolished either by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, an intracellular Ca2+ chelator, or by KN-62, an inhibitor of calcium-calmodulin-dependent protein kinase II (CaM kinase II). On the other hand, phorbol 12-myristate 13-acetate (PMA, 0.5 microM) did not affect the apical Na+/H+ exchanger but did stimulate the basolateral Na(+)-HCO3- cotransporter by 60-80%, and this stimulation was prevented by calphostin C, an inhibitor of PKC. Consistent with the cotransporter stimulation, PMA decreased steady-state pHi in the presence of CO2/ HCO3-. These results indicate that 1) the acute increase in [Ca2+]i within physiological ranges inhibits the apical Na+/H+ exchanger, probably through mediation of CaM kinase II; and 2) the short-term PKC activation stimulates the basolateral Na(+)-HCO3- cotransporter.
Mechanism of diuresis during negative pressure breathing
Authors: Boylan John W. , Antkowiak Dorothy E.
Published: December 2017

The diuresis associated with negative pressure breathing in moderately hydrated man is found to be due chiefly to an increase in the excretion of free water; solute excretion rises slightly and consistently. Simultaneous clearance studies do not reveal a characteristic pattern in renal hemodynamics for diuresis is observed to attend an increase, decrease or absence of change in RPF and GFR. There is, moreover, no effect on the peripheral venous hematocrit nor on the osmolar concentration of the plasma. Negative pressure breathing is without effect on urine flow when performed during maximal water diuresis or during the antidiuresis produced by infused Pitressin. These observations are in accord with the theory that the effective mechanism for the diuresis of negative pressure breathing is a reflex inhibition of antidiuretic hormone secretion.

Submitted on September 19, 1958
Relationship between nonprotein sulfhydryl concentration of seminal fluid and motility of spermatozoa in man
Authors: Haag Fritz M. , MacLeod John
Published: December 2017

The nonprotein sulfhydryl content of human seminal fluid was measured and an inverse correlation between the -SH titer and the motility of the spermatozoa in the fluid over a 5-hour period was found. The same inverse correlation, with less significance, was shown between the -SH titer and the percentage of active cells, semen quality and volume of ejaculates. No correlation between the -SH concentration and the sperm count was detectable. The nonprotein -SH titer was identified qualitatively and quantitatively as ergothioneine. The concentration in human seminal fluid is 1.5 mg %, a value close to that found in human blood.

Submitted on July 17, 1958
Physiologic, biochemical, immunologic and pathologic changes following ozone exposure
Authors: Scheel Lester D. , Dobrogorski Olga J. , Mountain John T. , Svirbely Joseph L. , Stokinger Herbert E.
Published: December 2017

A detailed study of physiologic, biochemical, immunologic and pathologic changes resulting from acute and repeated acute injuries due to inhalation of ozone is reported. This study defines the primary chemical reaction of ozone with constituents of the body, the response of the body to the presence of the toxic substance, the physiologic functional alterations produced by acute and repeated acute injuries due to inhalation of this gas and the pathology produced by these injuries in rabbits, mice and rats. The data presented show that ozone reacts with the proteins of lung tissue to produce a severe cellular irritation which alters cell wall permeability and leads to severe pulmonary edema. Repeated acute injuries are shown to cause the development of fibrosis of the bronchioles and alveolar ducts, which limits the reserve capacity of the lung by causing the Hering-Breuer reflex to stop inspiration before complete inhalation can take place. Immunologic and biochemical changes observed which are characteristic of this type of injury are reported. It has been shown that ozone reacts in a random fashion with proteins to produce a heterogeneous antigen which will stimulate an antibody response in rabbits. The antigen created was shown to have characteristics similar to denatured protein. The severe limitation of pulmonary function by reduced tidal volume and edema and the resulting pathologic changes are reported and discussed.

Submitted on July 7, 1958
Failure of manual respiration
Authors: Safar Peter
Published: December 2017

The tidal volumes moved during performance of the BPAL and CPAL methods in 29 curarized, anesthetized, apneic adults were measured with a spirometer through an oronasal mask (with and without an artificial oropharyngeal airway in place) and through a tracheal tube. With the conventional BPAL method without an artificial airway the average tidal volume was zero, or less than dead space air in 12 of 15 subjects studied. The failure was mainly due to pharyngeal obstruction by the relaxed tongue, occurring when the neck was flexed and the mandible was not supported. An artificial oropharyngeal airway only slightly improved the tidal exchange. A modified BPAL method, which consisted of the head being tilted backward, increased the tidal volume and decreased the incidence of obstruction. With the conventional CPAL method the tidal volumes likewise depended mainly on the position of the head and neck. A modified CPAL method, which consisted of maintaining the head tilted backward by elevating the shoulders, was compared in 10 subjects with the modified BPAL method. The tidal volumes were greater and the incidence of upper airway obstruction was lower with the modified CPAL method. With a tracheal tube in place, tidal volumes of 260–840 ml were moved without signs of airway obstruction. The low values occurred in short and obese patients with reduced lung-thorax compliance.

Submitted on August 28, 1958
Anatomical subdivisions of the volume of respiratory dead space and effect of position of the jaw
Authors: Nunn J. F. , Campbell E. J. M. , Peckett B. W.
Published: December 2017

The mean volume of the extrathoracic respiratory tract in six cadavers was found to be 72 ml (BTPS), (S.D. ±32). Expressed as a fraction of body weight in pounds this amounted to 0.55. The intrathoracic anatomical dead space was measured in three intubated subjects. The mean value was 66 ml (BPTS), (S.D. ±29) or 0.43 times the body weight in pounds. The influence of the position of the jaw on the dead space was studied in the six cadavers and three conscious subjects. Depression of the jaw with flexion of the neck produced a mean decrease in the dead space of 31.4 ml while a protrusion of the jaw with extension of the neck increased the dead space by 39.7 ml.

Submitted on July 28, 1958
Uneven ventilation of normal and diseased lungs studied by an open-circuit method
Authors: Briscoe William A. , Cournand Andre
Published: December 2017

The uneven ventilation of the lungs of six normal, four emphysematous and four other subjects was studied by an open-circuit method, using 11% helium in air as the indicator gas. The volume and ventilation of two groups of alveoli, one more and one less ventilated, were assessed in most cases. A new graphic method of dealing with open-circuit mixing data is presented. The results are discussed and compared with those of others. Normal lungs can be said to behave as if about half their volume was half as well ventilated as the rest of the lung. Emphysematous lungs can be said to behave as if three-quarters of the lung was only about one-fifth to one-tenth as well ventilated as the remaining quarter.

Submitted on October 3, 1958
Temperature thresholds for cutaneous pain
Authors: Neisser Ulric
Published: December 2017

Thresholds for pricking pain, as well as withdrawal points and endurance limens, were measured in 40 untrained subjects. The measurements were made in terms of the instantaneous temperature of the skin during thermal irradiation. The thresholds were lower and more variable for these subjects than for highly trained ones. They varied with the region of skin stimulated, ranging from 40.8℃ on the palm to 42.2℃ on the forehead, and were about 1℃ higher on skin blackened with India ink than on normal skin. Adaptation to pain occurred regularly, sensitivity being decreased in repeated measurements. Implications for pain threshold measurements in general are discussed.

Submitted on March 31, 1958
Reproducibility of cardiac output measurements in the dog
Authors: Howell Charles D. , Horvath Steven M.
Published: December 2017

Studies were performed on dogs to determine the constancy of the cardiac output during a 4-hour period beginning from the moment the animal was anesthetized. The cardiac output fell to varying quantities during the first hour but finally became stabilized at approximately 50–75% of the values obtained within the first 2–3 minutes following induction. Considerable variability in this response among different animals was noted. Similar studies on other animals, beginning approximately 1 hour following induction, indicated a similar pattern, i.e. that relatively stable cardiac outputs could be anticipated after this time period.

Submitted on July 16, 1958
Relationship between endoesophageal and intrathoracic pressure variations in dog
Authors: Milic-Emili G. , Petit J. M.
Published: December 2017

In two dogs, intrathoracic and endoesophageal pressure were simultaneously recorded. Between intrathoracic and endoesophageal pressure variations a difference of magnitude was found, depending upon a) the elastance of the esophageal walls and b) the volume/pressure coefficient of the measuring equipment of the endoesophageal pressure. Knowing a) and b) from endoesophageal pressure measurements, intrathoracic pressure variations may be calculated.

Submitted on December 15, 1958
Sodium and potassium content of brain and muscle of rats subjected to high acceleration
Authors: Burgess Benjamin F. , Gell Charles F. , Cranmore Doris
Published: December 2017

Male Albino (Wistar) rats were subjected to a radial acceleration stress on an eight-foot centrifuge. Each centrifugation of 20 positive g (head to foot) lasted 20 seconds followed by a 1-minute rest period. The stress pattern consisted of 40 exposures to this sublethal stress in approximately 1 hour. The entire brain and a section of the rectus femoris muscle were removed and analyzed for their sodium and potassium content. There was a significant decrease in muscle and brain potassium and a significant increase in muscle sodium; brain sodium remained unchanged. In one series of rats a sublethal intraperitoneal injection of sodium amytal was given 3 minutes prior to decapitation. In contrast to the unanesthetized series, this group showed an increase in brain potassium in the stress animals.

Submitted on January 14, 1959
Partial extracorporeal circulation in closed-chest dogs
Authors: Galletti Pierre M. , Salisbury Peter F.
Published: December 2017

In anesthetized dogs a fraction of the venous blood flow was diverted into a heart-lung machine (gas exchange bag) and from there infused by gravity into the arterial circulation. During such a partial heart-lung bypass an increase in extracorporeal perfusion rate resulted in a long lasting bradycardia and a decrease of right ventricular pressure and pulmonary blood flow. The decline of the aortic pressure caused by this maneuver could be compensated by adjustment of the infusion pressure into the arterial system. The external work of the heart was reduced thereby without compromising tissue perfusion. The procedure was compatible with survival of the animals.

Submitted on February 24, 1959
Circulating levels of 17-hydroxycorticosteroid in prolonged hypothermia
Authors: Barlow George , Spurr G. B. , Bowe Robert L.
Published: December 2017

Thirty nonsurgically stressed dogs, anesthetized with pentobarbital sodium, were subjected to hypothermia induced by surface cooling. Plasma volumes, plasma 17-hydroxycorticosteroid concentrations and circulating amounts of corticoid were measured at rectal temperatures of 33°, 30°, 28°, 25° and, after 2 and 4 hours, at 25℃. No significant differences were encountered with respect to the plasma concentration of 17-hydroxycorticoid. Plasma volumes were significantly reduced in every instance. Adrenal cortical responsiveness was tested with exogenous ACTH in four dogs. It is concluded that hypothermia in the pentobarbitalized dog does not evoke adrenal cortical response as measured by peripheral arterial blood levels of 17-hydroxycorticosteroids.

Submitted on August 21, 1958