bluuebunny/crossref_metadata_2025 huggingface dataset:
Vagotomy attenuates tumor necrosis factor-α-induced sleep and EEG δ-activity in rats
Authors: Kubota Takeshi , Fang Jidong , Guan Zhiwei , Brown Richard A. , Krueger James M.
Published: December 2017

Much evidence suggests that tumor necrosis factor-α (TNF-α) is involved in the regulation of physiological sleep. However, it remains unclear whether peripheral administration of TNF-α induces sleep in rats. Furthermore, the role of the vagus nerve in the somnogenic actions of TNF-α had not heretofore been studied. Four doses of TNF-α were administered intraperitoneally just before the onset of the dark period. The three higher doses of TNF-α (50, 100, and 200 μg/kg) dose dependently increased nonrapid eye movement sleep (NREMS), accompanied by increases in electroencephalogram (EEG) slow-wave activity. TNF-α increased EEG δ-power and decreased EEG α- and β-power during the initial 3 h after injection. In vagotomized rats, the NREMS responses to 50 or 100 μg/kg of TNF-α were attenuated, while significant TNF-α-induced increases in NREMS were observed in a sham-operated group. Moreover, the vagotomized rats failed to exhibit the increase in EEG δ-power induced by TNF-α intraperitoneally. These results suggest that peripheral TNF-α can induce NREMS and vagal afferents play an important role in the effects of peripheral TNF-α and EEG synchronization on sleep. Intraperitoneal TNF-α failed to affect brain temperature at the doses tested, thereby demonstrating that TNF-α-induced sleep effects are, in part, independent from its effects on brain temperature. Results are consistent with the hypothesis that a cytokine network is involved in sleep regulation.
IGFs stimulate zebrafish cell proliferation by activating MAP kinase and PI3-kinase-signaling pathways
Authors: Pozios Kasiani C. , Ding Jun , Degger Brian , Upton Zee , Duan Cunming
Published: December 2017

Insulin-like growth factor (IGF)-I and -II have been cloned from a number of teleost species, but their cellular actions in fish are poorly defined. In this study, we show that both IGF-I and -II stimulated zebrafish embryonic cell proliferation and DNA synthesis in a concentration-dependent manner, whereas insulin had little mitogenic activity. Affinity cross-linking and immunoblotting studies revealed the presence of IGF receptors with the characteristics of the mammalian type I IGF receptor. Competitive binding assay results indicated that the binding affinities of the zebrafish IGF-I receptors to IGF-I, IGF-II, and insulin are 1.9, 2.6, and >190 nM, indicating that IGF-I and -II bind to the IGF-I receptor(s) with approximately equal high affinity. To further investigate the cellular mechanism of IGF actions, we have studied the effects of IGFs on two major signal transduction pathways: mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3 kinase). IGFs activated MAPK in zebrafish embryonic cells in a dose-dependent manner. This activation occurred within 5 min of IGF-I stimulation and disappeared after 1 h. IGF-I also caused a concentration-dependent activation of protein kinase B, a downstream target of PI3 kinase, this activation being sustained for several hours. Inhibition of MAPK activation by the MAPK kinase inhibitor PD-98059 inhibited the IGF-I-stimulated DNA synthesis. Similarly, use of the PI3 kinase inhibitor LY-294002 also inhibited IGF-I-stimulated DNA synthesis. When both the MAPK and PI3 kinase pathways were inhibited using a combination of these compounds, the IGF-I-stimulated DNA synthesis was completely negated. These results indicate that both IGF-I and -II are potent mitogens for zebrafish embryonic cells and that activation of both the MAPK and PI3 kinase-signaling pathways is required for the mitogenic action of IGFs in zebrafish embryonic cells.
Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration
Authors: Convertino Victor A.
Published: December 2017

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (Q̊), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%ΔLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5–7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 ± 1.2 vs. 3.9 ± 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (−1.4 ± 0.2 vs. −2.6 ± 0.3 U/mmHg, P = 0.01), and higher HR (−1.2 ± 0.2 vs. −0.5 ± 0.1 beats · min−1 · mmHg−1, P = 0.01) and α-adrenoreceptor response (32.8 ± 3.4 vs. 19.5 ± 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in Q̊ and SV, %ΔLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 ± 496 vs. 5,438 ± 228 ml, P = 0.07) and erythrocyte (3,110 ± 364 vs. 2,310 ± 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.
Nitric oxide increases fluid extravasation from the splenic circulation of the rat
Authors: Andrew Peter S. , Deng Yiming , Sultanian Richard , Kaufman Susan
Published: December 2017

We hypothesized that nitric oxide (NO) contributes to intrasplenic fluid extravasation by inducing greater relaxation in splenic resistance arteries than veins such that intrasplenic microvascular pressure (PC) rises. Fluid efflux was estimated by measuring the difference between splenic blood inflow and outflow. Intrasplenic infusion of the NO donor S-nitroso- N-acetylpenicillamine (SNAP) (0.3 μg · 10 μl−1 · min−1) caused a significant increase in intrasplenic fluid efflux (baseline: 0.8 ± 0.4 ml/min, n = 10 vs. peak rise during SNAP infusion: 1.3 ± 0.4 ml/min, n = 10; P < 0.05). Intrasplenic PC was measured in the isolated, blood-perfused rat spleen. Intrasplenic infusion of SNAP (0.1 μg · 10 μl−1 · min−1) caused a significant increase in PC (saline: 10.9 ± 0.2 mmHg, n = 3 vs. SNAP: 12.2 ± 0.2 mmHg, n = 3; P < 0.05). Vasoreactivity of preconstricted splenic resistance vessels to sodium nitroprusside (SNP) (1 × 10−12-1 × 10−4 M) and SNAP (1 × 10−10-3 × 10−4 M) was investigated with the use of a wire myograph system. Significantly greater relaxation of arterioles than of venules occurred with both SNP (%maximal vasorelaxation: artery 96 ± 2.3, n = 9 vs. vein 26 ± 1.9, n = 10) and SNAP (%maximal vasorelaxation: artery 50 ± 3.5, n = 11 vs. vein 32 ± 1.7, n = 8). These results are consistent with our proposal that differential vasoreactivity of splenic resistance arteries and veins to NO elevates intrasplenic PC and increases fluid extravasation into the systemic lymphatic system.
Acute exercise induced changes in rat skeletal muscle mRNAs and proteins regulating type IV collagen content
Authors: Koskinen S. O. A. , Wang W. , Ahtikoski A. M. , Kjær M. , Han X. Y. , Komulainen J. , Kovanen V. , Takala T. E. S.
Published: December 2017

This experiment tested the hypothesis that running-induced damage to rat skeletal muscle causes changes in synthesis and degradation of basement membrane type IV collagen and to proteins regulating its degradation. Samples from soleus muscle and red and white parts of quadriceps femoris muscle (MQF) were collected 6 h or 1, 2, 4, or 7 days after downhill running. Increased muscle β-glucuronidase activity indicated greater muscle damage in the red part of MQF than in the white part of MQF or soleus. In the red part of MQF, type IV collagen expression was upregulated at the pretranslational level and the protein concentration decreased, whereas matrix metalloproteinase-2 (MMP-2), a protein that degrades type IV collagen, and tissue inhibitor of metalloproteinase-2 (TIMP-2), a protein that inhibits degradation, were increased in parallel both at mRNA and protein levels. Type IV collagen mRNA level increased in the white part of MQF and soleus muscle. The protein concentration increased in the white part of MQF and was unchanged in soleus muscle. MMP-2 and TIMP-2 changed only slightly in the white part of MQF and soleus muscle. The changes seem to depend on the severity of myofiber injury and thus probably reflect reorganization of basement membrane compounds.
Meal-related stimuli differentially induce c-Fos activation in the nucleus of the solitary tract
Authors: Emond Michael , Schwartz Gary J. , Moran Timothy H.
Published: December 2017

Feedback signals arising from the oral cavity and upper gastrointestinal tract contribute to the control of meal size. To assess how these signals are integrated at central sites involved in ingestive control, we compared levels of c-Fos activation in the nucleus of the solitary tract (NTS) and area postrema (AP) in response to meal ingestion or gastric and duodenal infusions in the rat. Ingestion of a liquid diet to satiety induced significant fos-like immunoreactivity (FLI) at multiple levels of the NTS and within the AP. The restriction of intake to one-half the normal ingestion of a rat did not result in significant FLI, although gastric infusion of this liquid diet volume did. Fast bolus infusion resulted in greater FLI than did the same volume infused at a rate to mimic that of normal ingestion. Prior experience with gastric infusions did not affect the amounts of FLI within the NTS or AP. In rats with pyloric cuffs blocking flow from the stomach to the intestine, combined gastric load and duodenal nutrient elicited significantly greater FLI than either gastric or duodenal infusions alone. These data demonstrate that neural activation arising from meal-related stimuli are integrated at the level of the NTS.
Effects of estrogen on thermoregulatory tail vasomotion and heat-escape behavior in freely moving female rats
Authors: Hosono Takayoshi , Chen Xiao-Ming , Miyatsuji Aya , Yoda Tamae , Yoshida Kyoko , Yanase-Fujiwara Motoko , Kanosue Kazuyuki
Published: December 2017

Effects of estrogen on thermoregulatory vasomotion and heat-escape behavior were investigated in ovariectomized female rats supplemented with estrogen (replaced estrogen rats) or control saline (low estrogen rats). First, we measured tail temperature of freely moving rats at ambient temperatures (Ta) between 13 and 31°C. Tail temperature of the low estrogen rats was higher than that of the replaced estrogen rats at Ta between 19 and 25°C, indicating that the low estrogen rats exhibit more skin vasodilation than the replaced estrogen rats. There was no significant difference in oxygen consumption and core temperature between the two groups. Second, we analyzed heat-escape behaviors in a hot chamber where rats could obtain cold air by moving in and out of a reward area. The low estrogen rats kept Ta at a lower level than did the replaced estrogen rats. These results imply that the lack of estrogen facilitates heat dissipation both by skin vasodilation and by heat-escape behavior. Ovariectomized rats may mimic climacteric hot flushes not only for autonomic skin vasomotor activity but also for thermoregulatory behavior.
Enhanced renal expression of preproendothelin mRNA during chronic angiotensin II hypertension
Authors: Alexander Barbara T. , Cockrell Kathy L. , Rinewalt A. Nicole , Herrington Jason N. , Granger Joey P.
Published: December 2017

The purpose of this study was to determine the role of endothelin in mediating the renal hemodynamic and arterial pressure changes observed during chronic ANG II-induced hypertension. ANG II (50 ng · kg−1 · min−1) was chronically infused into the jugular vein by miniosmotic pump for 2 wk in male Sprague-Dawley rats with and without endothelin type A (ETA)-receptor antagonist ABT-627 (5 mg · kg−1 · day−1) pretreatment. Arterial pressure increased in ANG II rats compared with control rats (149 ± 5 vs. 121 ± 6 mmHg, P< 0.05, respectively). Renal expression of preproendothelin mRNA was increased by ∼50% in both the medulla and cortex of ANG II rats. The hypertensive effect of ANG II was completely abolished in rats pretreated with the ETA-receptor antagonist (114 ± 5 mmHg, P < 0.05). Glomerular filtration rate was decreased by 33% in ANG II rats, and this response was attenuated in rats pretreated with ETA-receptor antagonist. These data indicate that activation of the renal endothelin system by ANG II may play an important role in mediating chronic renal and hypertensive actions of ANG II.
Suppression and recovery of estrous behavior in Syrian hamsters after changes in metabolic fuel availability
Authors: Jones Juli E. , Lubbers Laura S.
Published: December 2017

A reduction in the availability of oxidizable metabolic fuels inhibits reproduction. Forty-eight hours of metabolic fuel deprivation inhibits estrous behavior in ovariectomized, steroid-treated Syrian hamsters, but little is known about the time course of this inhibition. Likewise, refeeding reverses deprivation-induced suppression, but the rate of recovery has not been examined. In two experiments we determined 1) the rate at which estrous behavior declines in hamsters treated with metabolic inhibitors and 2) how rapidly sexual receptivity is restored when hamsters are refed after a 48-h fast. We also measured circulating levels of leptin and insulin in an attempt to determine their relationship to the inhibition and restoration of estrous behavior. More than 24 h of metabolic inhibitor administration were required to inhibit lordosis, whereas only 6 h of refeeding were sufficient to restore the display of sexual receptivity to normal levels. Neither plasma insulin nor leptin levels paralleled the changes in estrous behavior. We concluded that 1) suppression of estrous behavior occurs more slowly than recovery after a fast and 2) changes in circulating leptin and insulin probably do not have a critical role in these behavioral changes.
A novel pharmacological action of ET-1 to prevent the cytotoxicity of doxorubicin in cardiomyocytes
Authors: Suzuki Takahiko , Miyauchi Takashi
Published: December 2017

We previously reported that cardiomyocytes produce endothelin (ET)-1 and that the tissue level of ET-1 markedly increased in failing hearts in rats with chronic heart failure. Because the level of plasma ET-1 also increased progressively in patients with breast cancer who received doxorubicin (Dox; Adriamycin), which possesses cardiotoxicity, we hypothesized that ET-1 plays a role in the pathophysiology of cardiomyocytes injured by Dox. In this study, we investigated the effect of ET-1 on the cytotoxicity of Dox in primary cultured neonatal rat cardiomyocytes. The results showed that ET-1 effectively attenuated Dox-induced acute cardiomyocyte cytotoxicity (24-h incubation with Dox) evaluated by in vitro cell toxicity assay {3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay and lactate dehydrogenase release}. The cytoprotective effect of ET-1 was mediated via ETAreceptors, because pretreatment with the ETA-receptor antagonist BQ123 completely suppressed the cytoprotective effect of ET-1, whereas the ETB-receptor antagonist BQ788 did not. The cytoprotective effect of ET-1 was abolished by pretreatment with cycloheximide or staurosporine. These results suggest that a protein molecule(s), which is synthesized de novo by the stimulation of protein kinase pathway, is involved in the cytoprotective effect of ET-1. ET-1 increased the expression of an endogenous antioxidant, manganese superoxide dismutase (Mn-SOD), in the cardiomyocytes, as demonstrated by a Western blotting analysis. Pretreatment with an antisense oligodeoxyribonucleotide of Mn-SOD markedly attenuated the cytoprotective effect of ET-1 on the Dox-induced cytotoxicity. However, under conditions of prolonged incubation with Dox (48 h), ET-1 did not affect Dox-induced cardiomyocyte cytotoxicity in culture. These results suggest that ET-1 prevents the early phase of Dox-induced cytotoxicity via the upregulation of the antioxidant Mn-SOD through ETAreceptors in cultured cardiomyocytes.
Recovery of force during postcontractile depression in singleXenopusmuscle fibers
Authors: Howlett Richard A. , Stary Creed M. , Hogan Michael C.
Published: December 2017

This study examined the relationship between force and cytosolic free calcium concentration ([Ca2+]c) in different fiber types from Xenopus before, during, and after cells underwent postcontractile depression (PCD). During a standardized fatigue run, force in the two fast fatiguing (FF) fiber types (types 1 and 2, n = 10) fell more quickly (5.8 vs. 8.1 min) and to a greater degree [0.36 vs. 0.51 of initial (Po)] than in the slow fatiguing (SF) fiber type (type 3, n = 11). After the initial fatigue run, both FF and SF experienced a drop in force to <15% Po(PCD) at a similar time (20.6 vs. 21.4 min). A second stimulation period, undertaken during PCD, produced significant recovery of force in both groups, but significantly more so in SF than FF (64 ± 7 vs. 29 ± 2% Po). This force recovery during PCD was accompanied by a significant increase in peak [Ca2+]c, particularly in SF. However, despite the significant recovery of force during stimulation while in PCD, the amount of force produced for a given peak [Ca2+]cwas significantly lower in both groups during PCD than at any other point in the experiment. A final stimulation period, initiated when all fibers had recovered from PCD, demonstrated a recovery of both force and peak [Ca2+]cin both groups, but this recovery was significantly greater in SF vs. FF. These data demonstrate that with continuous electrical stimulation, it is possible to produce a significant recovery of force production during the normally quiescent period of PCD, but that it occurs with a decreased muscle force production for a given peak [Ca2+]c. This suggests that factors other than structural alterations of the sarcoplasmic reticulum are likely the cause of PCD in these fibers.
Hemodynamic and hormonal effects of human ghrelin in healthy volunteers
Authors: Nagaya Noritoshi , Kojima Masayasu , Uematsu Masaaki , Yamagishi Masakazu , Hosoda Hiroshi , Oya Hideo , Hayashi Yujiro , Kangawa Kenji
Published: December 2017

To investigate hemodynamic and hormonal effects of ghrelin, a novel growth hormone (GH)-releasing peptide, we gave six healthy men an intravenous bolus of human ghrelin (10 μg/kg) or placebo and vice versa 1–2 wk apart in a randomized fashion. Ghrelin elicited a marked increase in circulating GH (15-fold). The elevation of GH lasted longer than 60 min after the bolus injection. Injection of ghrelin significantly decreased mean arterial pressure (−12 mmHg, P < 0.05) without a significant change in heart rate (−4 beats/min, P = 0.39). Ghrelin significantly increased cardiac index (+16%, P < 0.05) and stroke volume index (+22%, P < 0.05). We also examined ghrelin receptor [GH secretagogues receptor (GHS-R)] gene expression in the aortas, the left ventricles, and the left atria of rats by RT-PCR. GHS-R mRNA was detectable in the rat aortas, left ventricles, and left atria, suggesting that ghrelin may cause cardiovascular effects through GH-independent mechanisms. In summary, human ghrelin elicited a potent, long-lasting GH release and had beneficial hemodynamic effects via reducing cardiac afterload and increasing cardiac output without an increase in heart rate.
Molecular expression of myostatin and MyoD is greater in double-muscled than normal-muscled cattle fetuses
Authors: Oldham J. M. , Martyn J. A. K. , Sharma M. , Jeanplong F. , Kambadur R. , Bass J. J.
Published: December 2017

Excessive muscling in double-muscled cattle arises from mutations in the myostatin gene, but the role of myostatin in normal muscle development is unclear. The aim of this study was to measure the temporal relationship of myostatin and myogenic regulatory factors during muscle development in normal (NM)- and double-muscled (DM) cattle to determine the timing and possible targets of myostatin action in vivo. Myostatin mRNA peaked at the onset of secondary fiber formation ( P < 0.001) and was greater in DM ( P < 0.001) than in NM. MyoD expression was also elevated throughout primary and secondary fiber formation ( P < 0.001) and greater in DM ( P < 0.05). Expression of myogenin peaked later than MyoD ( P< 0.05); however, it did not differ between NM and DM. These data show that myostatin and MyoD increase coincidentally during formation of muscle fibers, indicating a coordinated role in the terminal differentiation and/or fusion of myoblasts. Myostatin mRNA is also consistently higher in DM than NM, suggesting that a feedback loop of regulation is also disrupted in the myostatin-deficient condition.
NO modulates norepinephrine release in human skeletal muscle: implications for neural preconditioning
Authors: Costa Fernando , Christensen Niels J. , Farley Ginnie , Biaggioni Italo
Published: December 2017

The purpose of this study was to estimate muscle interstitial norepinephrine (NE) levels during exercise and to determine whether nitric oxide (NO) modulates NE release in the skeletal muscle in humans. We measured interstitial dialysate concentrations of NE with two microdialysis probes inserted into the forearm. Probes were perfused with saline and the NO synthesis inhibitor N G-monomethyl-l-arginine (l-NMMA), respectively. Dialysate samples were collected during two sequential 20-min intense dynamic handgrip periods, preceded by 40-min baseline periods. On a different day, forearm ischemia was performed instead of the first exercise period. Exercise increased dialysate NE from 172 ± 42 to 270 ± 45 pg/ml (83% increase, P < 0.02, n = 6). Probes perfused with l-NMMA had a 136 ± 39% greater dialysate NE compared with probes perfused with saline (225 ± 25 vs. 125 ± 25 pg/ml, P < 0.001, n = 9). The exercise-induced increase in NE (125 ± 52%) was attenuated if preceded by exercise (34 ± 34%) or ischemia (40 ± 36%; P = 0.06, n = 6), suggesting a neural preconditioning effect. This attenuation was not observed in probes perfused withl-NMMA. We propose that NO modulates NE release in skeletal muscle, that ischemic exercise increases muscle interstitial NE, and that this increase can be attenuated by a preconditioning effect mediated in part by NO.
Amniotic fluid and hemodynamic model in monochorionic twin pregnancies and twin-twin transfusion syndrome
Authors: Umur Asli , Van Gemert Martin J. C. , Ross Michael G.
Published: December 2017

We developed a mathematical model of monochorionic twin pregnancies and twin-twin transfusion syndrome (TTTS), combining both fetal fluid dynamics and fetoplacental growth and circulation alterations and assuming that transplacental fluid flow from mother to fetus accounts for normal fetal and amniotic fluid volumes. Ten coupled differential equations, describing fetal total body and amniotic fluid volumes, their osmolalities, and fetal blood colloid osmotic pressure, for both donor and recipient twins, were solved numerically. Amniotic flows are controlled by fetal plasma osmolality and hydrostatic and colloid osmotic pressures. We included varying placental anastomoses and placental sharing of the circulations. Consistent with clinical experience, model predictions are: fetofetal transfusion from unidirectional arteriovenous anastomoses cause oligo-polyhydramnios, a normal size recipient but hypovolemic donor; compensating oppositely directed deep and superficial anastomoses moderate discordant development; and anhydramnios results from mild and severe TTTS, where milder forms may even present earlier in gestation than severe TTTS. Unequal placental circulatory sharing may exacerbate discordant development. In conclusion, our model simulates a wide variety of realistic manifestations of amniotic fluid volume and fetal growth in TTTS related to placental angioarchitecture. The model may allow an assessment of the efficacy of current therapeutic interventions for TTTS.
Evidence supporting a physiological role for proANP-(1–30) in the regulation of renal excretion
Authors: Dietz John R. , Scott Dionne Y. , Landon Carol S. , Nazian Stanley J.
Published: December 2017

The experiments, performed in pentobarbital sodium-anesthetized rats, consisted of a 1-h equilibration period followed by two 30-min control periods. Subsequently, synthetic rat pro atrial natriuretic peptide (ANP) [proANP-(1–30)] ( n = 8) was given as a bolus of 10 μg in 1 ml of 0.9% saline followed by an infusion at 30 ng/min (20 μl/min) for six additional periods. Control rats ( n = 6) received only 0.45% saline in the appropriate volumes. Mean arterial pressure, renal blood flow, and glomerular filtration rate did not change significantly in either group during the proANP-(1–30) infusion. Urine flow and potassium excretion increased ∼50% in the proANP-(1–30)-infused group only ( P < 0.05). Sodium excretion and fractional excretion of sodium, expressed as the change from their own baselines, were significantly increased by the proANP-(1–30) infusion ( P < 0.05), whereas cGMP excretion was similar in both groups. These results suggest that the rat sequence of proANP-(1–30) produces a natriuresis in the rat independent of changes in hemodynamics and renal cGMP production. In a second study, rats ( n = 8) were prepared as above and pretreated with 0.4 ml iv of rabbit serum containing an antibody directed against proANP-(1–30) (anti-proANP group). The rats were volume expanded with 3 ml of 6% albumin in Krebs and observed for 3 h to determine if the anti-proANP would attenuate the responses to volume expansion. Control rats ( n = 7) received 0.4 ml of normal rabbit serum. The elevation in potassium excretion in response to volume expansion was significantly attenuated in the anti-proANP group ( P < 0.05). Sodium excretion and urine flow responses also tended to be reduced but not significantly. These results suggest that in the rat, proANP-(1–30) plays a physiological role in regulating renal excretion.
Heat acclimation and heat stress have different effects on cholinergic-induced calcium mobilization
Authors: Kaspler Pavel , Horowitz Michal
Published: December 2017

There is evidence that the signal transduction array responsible for the secretion of water in evaporative cooling by the submaxillary gland of the rat is subject to heat acclimatory responses. The objectives of the present study were 1) to examine whether heat acclimation affects intracellular Ca2+mobilization and, in turn, submaxillary glandular responsiveness; 2) to assess whether the acclimatory responses differ from those evoked on heat stress (HS). Experiments were conducted on submaxillary glands of rats acclimated at 34°C for 0, 2 [short-term heat acclimation (STHA)], and 30 [long-term heat acclimation (LTHA)] days. The resting cytosolic calcium concentration ([Ca2+]c) and the carbamylcholine-evoked calcium signal ([Ca2+]s) of dispersed glandular cells were measured using the fluorescent dye fura 2 AM. Inositol-1,4,5-trisphosphate (IP3)-sensitive endoplasmic reticulum Ca2+stores were determined in permeabilized cells using fura 2 potassium salt. STHA resulted in a drop in both [Ca2+]sand IP3-sensitive Ca2+stores. On LTHA, the [Ca2+]samplitude reverted to the preacclimation value, whereas the IP3-sensitive Ca2+stores remained low. The drop in [Ca2+]son STHA is in accord with the decreased glandular output (measured by86Rb efflux) observed during this acclimation phase. However, after LTHA the enhanced glandular output despite reduced [Ca2+]slevels suggests an increased efficiency of cellular secretory mechanisms in that group. Collectively, the alterations in [Ca2+]ssupport our biphasic acclimation model (Horowitz M, Kaspler P, Marmari Y, and Oron Y. J Appl Physiol 80: 77–85, 1996.). In nonacclimated glands, HS caused an elevation in [Ca2+]scoincidentally with a decrease in the IP3Ca2+stores. In contrast, [Ca2+]sin both STHA and LTHA glands was not affected by HS, despite a marked increase in the IP3-sensitive Ca2+stores in the LTHA glands. The opposing responses to HS and heat acclimation in calcium signaling and stores confirm the specificity of each process.
Function of human intrinsic cardiac neurons in situ
Authors: Arora Rakesh Christopher , Hirsch Gregory Matthew , Hirsch Kristine Johnson , Friesen Camille Hancock , Armour John Andrew
Published: December 2017

We sought to determine the behavior of intrinsic cardiac neurons in human subjects undergoing cardiac surgery and to correlate their activity with hemodynamics status. A lead II electrocardiogram, pulmonary artery pressure, and systemic arterial pressure were recorded along with extracellular activity generated by right atrial neurons in 10 patients undergoing coronary artery bypass surgery. Identified neurons generated spontaneously activity that was, for the most part, unrelated to the cardiac cycle. Most neurons were activated by gentle mechanical distortion of ventricular epicardial loci. The activity generated by neurons in each patient increased when arterial pressure increased and decreased when arterial pressure fell. Intrinsic cardiac neurons continued to generate activity during cardioplegia and cardiopulmonary bypass, but at reduced levels. Normal neuronal activity was restored postbypass. It is concluded that human intrinsic cardiac neurons generate spontaneous activity and that many receive inputs from ventricular mechanosensory neurites. The latter may account for the fact that their behavior depends, in part, on cardiac dynamics. They are also sensitive to intravenously administered pharmacological agents. These data also indicate that cardiopulmonary bypass and cardioplegia do not induce residual depression of their function.
Neuronal histamine release elicited by hyperthermia mediates tracheal dilation and pressor response
Authors: Kanamaru Mitsuko , Iwase Michiko , Homma Ikuo
Published: December 2017

Whether brain histaminergic neurons contribute to the regulation of tracheal tone and peripheral vascular tone under hyperthermia was investigated in anesthetized rabbits. Histamine release from the rostral ventrolateral medulla (RVLM), the raphe nuclei, and the solitary nucleus of the medulla oblongata was significantly increased by hyperthermia. The increased histamine was significantly suppressed by 10−6 M tetrodotoxin microdialyzed in each area. Tracheal pressure and mean arterial pressure were significantly decreased and increased by hyperthermia, respectively. An H1-receptor antagonist, 5 × 10−6 M (+)-chlorpheniramine, bilaterally microdialyzed in the RVLM significantly enhanced histamine release in the RVLM as well as significantly suppressed tracheal dilation and pressor response caused by hyperthermia. These data indicate that histamine release in the medulla oblongata is enhanced by hyperthermia. The enhanced histamine is the neuronal origin and the cause of tracheal dilation and pressor response at least via H1 receptors in the RVLM. Brain histaminergic neurons play important roles in tracheal tone and peripheral vascular tone via H1 receptors in the RVLM and homeostasis on body temperature.
Mineralocorticoid treatment attenuates activation of oxytocinergic and vasopressinergic neurons by icv ANG II
Authors: Roesch Darren M. , Blackburn-Munro Ruth E. , Verbalis Joseph G.
Published: December 2017

Central oxytocin (OT) neurons limit intracerebroventricular (icv) ANG II-induced NaCl intake. Because mineralocorticoids synergistically increase ANG II-induced NaCl intake, we hypothesized that mineralocorticoids may attenuate ANG II-induced activation of inhibitory OT neurons. To test this hypothesis, we determined the effect of deoxycorticosterone (DOCA; 2 mg/day) on icv ANG II-induced c-Fos immunoreactivity in OT and vasopressin (VP) neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus and also on pituitary OT and VP secretion in male rats. DOCA significantly decreased the percentage of c-Fos-positive (%c-Fos+) OT neurons in the SON and PVN, both in the magnocellular and parvocellular subdivisions, and the %c-Fos+ VP neurons in the SON after a 5-ng icv injection of ANG II. DOCA also significantly reduced the %c-Fos+ OT neurons in the SON after 10 ng ANG II and tended to attenuate 10 ng ANG II-induced OT secretion. However, the %c-Fos+ OT neurons in DOCA-treated rats was greater after 10 ng ANG II, and DOCA did not affect the %c-Fos+ OT neurons in the PVN nor VP secretion or c-Fos immunoreactivity in either the SON or PVN after 10 ng ANG II. DOCA also did not significantly alter the effect of intraperitoneal (ip) cholecystokinin (62 μg) on %c-Fos+ OT neurons or of ip NaCl (2 ml of 2 M NaCl) on the %c-Fos+ OT and VP neurons. These findings indicate that DOCA attenuates the responsiveness of OT and VP neurons to ANG II without completely suppressing the activity of these neurons and, therefore, support the hypothesis that attenuation of OT neuronal activity is one mechanism by which mineralocorticoids enhance NaCl intake.
Urine and plasma proteins in men at 5,400 m
Authors: Rennie Drummond , Frayster Regina , Gray Gary , Houston Charles
Published: December 2017

Urine and plasma proteins were measured before, during, and after ascent from 800 to 5,400 m altitude on Mount Logan, in completely unacclimatized men who had made the ascent by plane in 40 min, and in acclimatized individuals who had climbed up and had lived at 5,400 m for 6 weeks. Protein excretion rates were increased, and creatinine excretion and clearance rates decreased, with increases in plasma creatinine levels, in both groups at 5,400 m. These changes were similar and therefore independent of acclimatization and of polycythemia. There was no evidence, from clearances of proteins and of polyvinylpyrrolidone, of any change in glomerular sieving, and the character of the proteinuria was qualitatively normal. Increases in plasma protein occurred only in those in whom there was evidence of dehydration. In the unacclimatized, after abrupt ascent, transferrin levels were decreased, possibly as a means of enhancing iron supply to the developing red cells, but after acclimatization transferrin levels rose to above normal levels.

hypoxia; altitude; proteinuria
Acceleration time series resulting from repetitive extension-flexion of the hand
Authors: Stiles R. N.
Published: December 2017

Power, or variance, spectra of acceleration records obtained from normal subjects during extension-flexion oscillations of a hand at frequencies between 0.5–5.0 Hz generally contained two or three frequency bands. Partial separation of these oscillations in the time domain was obtained using the method of digital filtering (smoothing). In general, the peak frequency of the lowest frequency band occurred at, or nearly at, the frequency that the subject attempted to maintain during a 16-s digitization period. Consideration of absolute frequencies and the effect of mass on frequency indicated that one of the higher frequency bands was the result of normal hand tremor. For low frequencies of voluntary oscillation (0.5–1.25 Hz), a second, higher frequency band occurred with a peak frequency (3.0–4.25 Hz) within the range (3–6 Hz) usually reported for abnormal hand tremor. For voluntary oscillation frequencies above about 1.5 Hz, this second, higher frequency oscillation generally occurred at twice the frequency of the voluntary oscillation.
Maximum permissible weight to be carried on the head by a male worker from eastern India
Authors: Datta S. R. , Chatterjee B. B. , Roy B. N.
Published: December 2017

Six healthy adult male Indian workers whose physical characteristics resembled those of the average worker from eastern India, were required to carry compact loads of 20, 30, 40, and 50 kg at a speed of 5 km/h on separate days. From observations on energy expenditures, of peak pulse rates, and of the patterns of recovery pulse rates, it was decided that for the average eastern Indian male worker the permissible weight of a compact load for manual carriage on a hard, level terrain should not ordinarily be more than 30 kg.
Effect of positive-pressure breathing on aADN2 in hyaline membrane disease
Authors: Corbet A. J. , Ross J. A. , Beaudry P. H. , Stern L.
Published: December 2017

In seven subjects with hyaline membrane disease and breathing 40–70% oxygen in nitrogen, the effect of continuous positive-pressure breathing (CPPB) was examined by application of a continuous negative pressure (10 cm water) about the thorax and assessment of the alveolar-arterial tension differences for nitrogen (aADn2) and oxygen (AaDo2). On CPPB, there was a decrease in the aADn2 by a mean 9 mmHg and a decrease in the AaDo2 by a mean 44 mmHg. This corresponded to a decrease in the total venous admixture (Qva/Qt) of 0.20 and to a decrease in the venous admixture due to a true right-to-left shunt (Qs/Qt) of 0.19. These data were interpreted to mean a significant improvement in Va/Qc imbalance within open ventilated parts of the lung, which could be responsible, particularly by relief of local alveolar hypoxia, for reduction of the pulmonary vascular resistance and the true right-to-left shunt.
Effect of added elastances on the first loaded breath in man
Authors: Pengelly L. D. , Greener J. , Bowmer I. , Luterman A. , Milic-Emili J.
Published: December 2017

Tidal volume together with end-inspiratory pressure was measured in four seated healthy men, during normal breathing and during single inspirations taken from a series of rigid containers which provided added elastances (range: 5–70 cmH2O/l). Experiments were performed both during quiet breathing and during ventilation increased by added dead space. Added elastic loads always resulted in a decreased tidal volume. This decrease was partly compensated by increased pressure developed by the inspiratory muscles; being more so with greater added elastance, control ventilation, or both. Analysis of our results indicates that the load-compensatory response may be attributed to changes in mechanical impedance of the ventilatory pump, due to the mechanical arrangement and the intrinsic properties of the inspiratory muscles (force-length and force-velocity relationships), changes in respiratory frequency with increasing ventilation, and to vagally mediated load compensation.
Effects of changes in PaCO2 on pulmonary input impedance
Authors: Foex P. , Prys-Roberts C.
Published: December 2017

Pulmonary arterial input impedance spectra were computed in goats in whom the appropriate pressure and flow transducers had been chronically implanted. In response to either hypocapnia or hypercapnia, under anesthesia (1% halothane in a 70% nitrous oxide--30% oxygen mixture) there were no significant modifications of impedance at zero frequency; no consistent or significant changes in the impedance moduli at frequencies between 2 and 14 Hz were observed; the position of the first impedance minimum or the subsequent maximum was not modified; however, pulmonary vascular resistance increased significantly with hypercapnia. Although the load opposing right ventricular ejection was not modified by variation of Paco2, right ventricular work was reduced in response to hypocapnia and augmented in response to hypercapnia.
Glucagon and plasma catecholamine responses to graded and prolonged exercise in man
Authors: Galbo H. , Holst J. J. , Christensen N. J.
Published: December 2017

Eight men were studied during graded (47, 77, and 100% of maximal oxygen uptake) and prolonged (76%) exhaustive treadmill running. During graded exercise the glucagon concentration increased 35% from 81 plus or minus 7 pg/ml (mean and SE) at rest to 109 plus or minus 17 after the heaviest load. During prolonged exercise glucagon increased progressively to three times (226 plus or minus 40) the resting value. Norepinephrine increased from 0.40 plus or minus 0.06 ng/ml to 2.22 plus or minus 0.39, epinephrine from 0.07 plus or minus 0.01 to 0.42 plus or minus 0.13 during graded, and to 1.51 plus or minus 0.08 and 0.33 plus or minus 0.04, respectively, during prolonged exercise. Insulin concentrations were depressed during work except for the heaviest load. Fatty acids rose throughout prolonged exercise, whereas blood glucose significantly diminished 30 min afterward. Glucagon concentrations correlated significantly with norepinephrine and epinephrine concentrations during prolonged and with epinephrine during graded exercise. Although increments in catecholamines were similar, the glucagon secretion was larger during prolonged than during graded exercise. While increments in catecholamines might explain increased glucagon secretion during graded exercise, they cannot account completely for the rise of glucagon during prolonged exercise.
Coagulation studies during experimental hemoglobinemia in humans
Authors: Spector J. I. , Crosby W. H.
Published: December 2017

Infusion of autologous hemolyzed blood in humans has served as a model for various experimental investigations for many years. Numerous studies have shown this model to be unattended by any adverse clinical reactions. In this study evidence of subclinical disseminated intravascular coagulation (DIC) was sought in normal humans infused with autologous hemolyzed blood. Hemoglobinemia was induced in 10 experiments by a single injection of frozen-thawed blood and in 4 experiments by such an injection of hemolysate followed by a 5-h maintenance infusion. Mean peak plasma hemoglobin following single dose injections was 540 mg/100 ml, while levels during continuous infusion averaged 240 mg/100 ml. The induction of hemoglobinemia was asymptomatic. Coagulation studies showed no significant alteration in prothrombin time, partial thromboplastin time, thrombin time, clottable fibrinogen, or WBC. Fibrin degradation products were not found. Platelet counts fell slightly in the 5-min postinfusion sample but returned to preinfusion levels within 30 min, suggesting a temporary sequestration of platelets rather than consumption. The induction of moderate brief experimental hemoglobinemia in normal subjects did not result in the development of demonstrable DIC.
Constituents of human muscle in isometric fatigue
Authors: Karlsson J. , Funderburk C. F. , Essen B. , Lind A. R.
Published: December 2017

Three subjects performed five successive isometric contractions to fatigue; the tension in any one experiment was constant at tensions varying from 20 to 80% of the maximal voluntary contraction (MVC). The interval between contractions was held constant at 11 min. Muscle biopsy specimens were obtained at the start of the experiment, after the first, fourth, and fifth, and before the second and fifth of the successive contractions. The concentrations of ATP, CP, glycogen, and lactate were measured in each sample of muscle. Changes in ATP and glycogen were insufficient to be held accountable for the development of isometric fatigue. Changes in CP and lactate were large after fatigue at intermediate tensions, but those of CP were considered unlikely to be responsible for the fatigue. At tensions of 30–50% MVC the increase in lactate could be responsible for fatigue either directly or by indirect changes in pH; at higher and lower tensions the possibility that lactate is directly implicated in the development of fatigue seems remote.
Rate factors in development of the high-pressure neurological syndrome
Authors: Brauer R. W. , Beaver R. W. , Mansfield W. M. , O'Connor F. , White L. W.
Published: December 2017

The effect of varying the pressure/time profile upon development of tremors and convulsions of the high-pressure neurological syndrome was studied in adult mice and squirrel monkeys and in baby mice. Two distinct response patterns were observed. In the adults rapid compression produces early onset of convulsions; convulsions subside rapidly when animals are held at constant pressure just above the convulsion point; and interrupted compression schedules show that total compression time rather than instantaneous compression rate at the moment seizures develop is the controlling parameter. Baby mice up to 12 days of age, by contrast, fail to show any perceptible relation between compression rate and convulsion threshold pressure (Pc); their seizures continue for a considerable period of time after a constant pressure level just above the convulsion threshold has been reached; and interrupted compressions of type a fail to change their convulsion threshold. Together with supplementary data regarding tremor thresholds and the transient increase of convulsion thresholds by prior seizures these results lead to a proposed schema describing these phenomena in terms of a pressure-dependent primary event predisposing to tremors and convulsions; a time-dependent event counteracting the convulsions (absent in baby mice); and a transient effect of prior convulsions, raising subsequent Pc.
Relative susceptibility of altitude-acclimatized mice to acute oxygen toxicity
Authors: Hall P. , Schatte C. L. , Fitch J. W.
Published: December 2017

The influence of hypoxic acclimatization at altitudes of 0, 5,000, or 15,000 ft on the relative susceptibility to acute oxygen poisoning was determined in 288 adult female mice. After acclimatization periods of 1, 2, 4, or 8 wk, the mice were exposed to oxygen at high pressures (OHP) of 4, 6, or 9 ATA and the times to convulsion and death recorded. A factorial analysis of variance indicated that altitude and OHP level had inverse, log-linear effects on both parameters. The duration of acclimatization progressively decreased the time to death. The onset of convulsions and death was independent of body weight. There were significant interactions on the measured parameters between various combinations of altitude, OHP level, and duration of acclimatization. While alterations in the metabolism of gamma-aminobutyric acid and high-energy compounds are common to both hypoxia and hyperoxia, the most plausible explanation of the results relates to the decrease in buffer base induced by hypoxic acclimatization which might have caused CO2 potentiation of OHP symptoms.
Changes of thermal balance induced by passive heating in resting man
Authors: Henane R. , Bittel J.
Published: December 2017

Heat acclimatization has been induced in 12 resting healthy men by 90-min exposure to 45C dry bulb and 24% relative humidity for 9 successive days. The most significant results ovserved were 1) increased sensitivity of sweating with marked quickening of sweat measured, 2) decreased rate of body heat storage associated with a lower rectal temperature at end of exposure, as follows: 14.07 plus or minus 1.58 Wtimeshtimeskg-1 before and 9.39 plus or minus 1.69 afterward for body heat storage; 37.55 plus or minus 0.15C before and 36.99 plus or minus 0.24C afterward for rectal temperature. In contrast, no significant changes were observed in the final sweat rates, mean skin temperatures, or the heat conductance between the body interior and skin surface. The quickness of the heat dissipation process caused by both increased sensitivity of sweating and lower internal body temperature is the major factor in achieving a thermal balance and a decreased body heat content after acclimatization.