bluuebunny/crossref_metadata_2025 huggingface dataset:
Antidipsogenic effects of eel bradykinins in the eelAnguilla japonica
Authors: Takei Yoshio , Tsuchida Takamasa , Li Zhihong , Conlon J. Michael
Published: December 2017

A peptide with bradykinin (BK)-like immunoreactivity was isolated from an incubate of heat-denatured eel plasma with porcine pancreatic kallikrein. The purified peptide had the following amino acid sequence: Arg-Arg-Pro-Pro-Gly-Ser-Trp-Pro-Leu-Arg. This decapeptide, named eel [Arg0]BK, was identical to two previously identified BK homologs from cod and trout. High conservation of the BK sequence among distant teleost species suggests an important function in this vertebrate group. Bolus intra-arterial injections of eel [Arg0]BK, BK, and [Arg0]-des-Arg9-BK (1–10 nmol/kg) caused significant ( P < 0.05) inhibition of drinking in seawater-adapted eels. The potency of the inhibition was ranked in the following order: [Arg0]BK > [Arg0]-des-Arg9-BK = BK. The BK peptides also produced an immediate, transient increase followed by a sustained increase in arterial blood pressure and an initial decrease followed by an increase in heart rate. Strong tachyphylaxis occurred for the cardiovascular effect but not for the antidipsogenic effect. The order of the potency of the cardiovascular actions, [Arg0]BK > BK > [Arg0]-des-Arg9-BK, was different from that of the antidipsogenic action. Slow infusions of eel [Arg0]BK in the dose range 1–1,000 pmol · kg−1 · min−1 produced concentration-dependent inhibition of drinking without changes in arterial pressure, plasma osmolality, and hematocrit. At the infusion rate of >100 pmol · kg−1 · min−1, plasma concentrations of angiotensin II, a potent dipsogenic hormone in eels, increased, suggesting an interaction of the kallikrein-kinin and renin-angiotensin systems. In mammals, BK is dipsogenic and vasodepressor, so that our data demonstrate opposite effects on fluid and cardiovascular regulation of BK in the eel and suggest a new physiological role for the kallikrein-kinin system in teleost fish.
Expression and functional activity of P-glycoprotein in cultured hepatocytes fromOncorhynchus mykiss
Authors: Sturm Armin , Ziemann Christina , Hirsch-Ernst Karen I. , Segner Helmut
Published: December 2017

P-glycoproteins encoded by multidrug resistance 1 ( mdr1) genes are ATP-dependent transporters located in the plasma membrane that mediate the extrusion of hydrophobic compounds from the cell. Using cultured isolated rainbow trout hepatocytes, we characterized an mdr1-like transport mechanism of the teleost liver. Immunoblots with the monoclonal antibody C219, which recognizes a conserved epitope of P-glycoproteins, revealed the presence of immunoreactive protein(s) of 165 kDa in trout liver and cultured hepatocytes. In trout liver sections, the immunohistochemistry with C219 stained bile canalicular structures. Compounds known to interfere with mdr1-dependent transport (verapamil, vinblastine, doxorubicin, cyclosporin A, and vanadate) all increased the accumulation of rhodamine 123 by hepatocytes. Verapamil, vinblastine, and cyclosporin A decreased the efflux of rhodamine 123 from hepatocytes preloaded with rhodamine 123. By contrast, the substrate of the canalicular cation transporter tetraethylammonium and the inhibitor of the multidrug resistance-associated protein MK571 had no effect on rhodamine 123 transport. The results demonstrate the presence of an mdr1-like transport system in the teleost liver and suggest its function in biliary excretion.
Expression of a chimeric retroviral-lipase mRNA confers enhanced lipolysis in a hibernating mammal
Authors: Bauer Vernon W. , Squire Teresa L. , Lowe Mark E. , Andrews Matthew T.
Published: December 2017

Hibernating mammals can survive several months without feeding by limiting their carbohydrate catabolism and using triacylglycerols stored in white adipose tissue (WAT) as their primary source of fuel. Here we show that a lipolytic enzyme normally found in the gut, pancreatic triacylglycerol lipase (PTL), is expressed in WAT of hibernating 13-lined ground squirrels ( Spermophilus tridecemlineatus). PTL expressed in WAT is encoded by an unusual chimeric retroviral-PTL mRNA ∼500 bases longer than the predominant PTL message found in other ground squirrel tissues. Seasonal measurements detect the chimeric mRNA and PTL enzymatic activity in WAT before and during hibernation, with both showing their lowest observed levels 1 wk after hibernation concludes in mid-March. PTL is expressed in addition to hormone-sensitive lipase, the enzyme typically responsible for hydrolysis of triacylglycerols in WAT. Because of the distinct catalytic and regulatory properties of both enzymes, this dual-triacylglycerol lipase system provides a means by which the fuel requirements of hibernating 13-lined ground squirrels can be met without interruption.
Effects of selective hyperglycemia and hyperinsulinemia on glucose transporters in fetal ovine skeletal muscle
Authors: Anderson Marianne S. , He Jing , Flowers-Ziegler Judy , Devaskar Sherin U. , Hay William W.
Published: December 2017

We measured net fetal glucose uptake rate from the placenta, shown previously to be equal to total fetal glucose utilization rate (GURf) and proportional to fetal hindlimb skeletal muscle glucose utilization, under normal conditions and after 1, 2.5, and 24 h of selective hyperglycemia (↑G) or selective hyperinsulinemia (↑I). We simultaneously measured the amount of Glut 1 and Glut 4 glucose transporter proteins in fetal sheep skeletal muscle. With ↑G, GURfwas increased ∼40% at 1 and 2.5 h but returned to the control rate by 24 h. This transient ↑G-specific ↑GURfwas associated with increased plasma membrane-associated Glut 1 (4-fold) and intracellular Glut 4 (3-fold) protein beginning at 1 h. With ↑I, GURfwas increased ∼70% at 1, 2.5, and 24 h. This more sustained ↑I-specific ↑GURfwas associated with a significant increase in Glut 4 protein (2-fold) at 2.5 h but no change in Glut 1 protein. These results show that ↑G and ↑I have independent effects on the amount of Glut 1 and Glut 4 glucose transporter proteins in ovine fetal skeletal muscle. These effects are time dependent and isoform specific and may contribute to increased glucose utilization in fetal skeletal muscle. The lack of a sustained temporal correlation between the increase in transporter proteins and glucose utilization rates indicates that subcellular localization and activity of a transporter or tissues other than the skeletal muscle contribute to net GURf.
Analysis of the afferent limb of the vesicovascular reflex using neurotoxins, resiniferatoxin and capsaicin
Authors: Chuang Yao-Chi , Fraser Matthew O. , Yu Yongbei , Beckel Jonathan M. , Seki Satoshi , Nakanishi Yasukazu , Yokoyama Hitoshi , Chancellor Michael B. , Yoshimura Naoki , de Groat William C.
Published: December 2017

The afferent limb of the vesicovascular reflex (VV-R) evoked by distension or contraction of the urinary bladder (UB) was studied in urethane-anesthetized female rats by examining the changes in VV-R after administration of C-fiber afferent neurotoxins [capsaicin and resiniferatoxin (RTX)]. Systemic arterial blood pressure increased parallel (5.1 to 53.7 mmHg) with graded increases in UB pressure (20 to 80 cmH2O) or during UB contractions. The arterial pressor response to UB distension was significantly reduced (60–85%) by acute or chronic (4 days earlier) intravesical administration of RTX (100–1,000 nM) or by capsaicin (125 mg/kg sc) pretreatment (4 days earlier). Chronic neurotoxin treatments also increased the volume threshold (>100%) for eliciting micturition in anesthetized rats but did not change voiding pressure. Acute RTX treatment (10–50 nM) did not alter the arterial pressor response during reflex UB contractions, whereas higher concentrations of RTX (100–1,000 nM) blocked reflex bladder contractions. It is concluded that VV-R is triggered primarily by distension- and contraction-sensitive C-fiber afferents located, respectively, near the luminal surface and deeper in the muscle layers of the bladder.
Physiological elevation in plasma angiotensinogen increases blood pressure
Authors: Klett Christoph P. R. , Granger Joey P.
Published: December 2017

Hepatic angiotensinogen secretion is controlled by a complex pattern of physiological or pathophysiological mediators. Because plasma concentrations of angiotensinogen are close to the Michaelis-Menten constant, it was hypothesized that changes in circulating angiotensinogen affect the formation rate of ANG I and ANG II and, therefore, blood pressure. To further test this hypothesis, we injected purified rat angiotensinogen intravenously in Sprague-Dawley rats via the femoral vein and measured mean arterial blood pressure after arterial catheterization. In controls, mean arterial pressure was 131 ± 2 mmHg before and after the injection of vehicle (sterile saline). The injection of 0.8, 1.2, and 2.9 mg/kg angiotensinogen caused a dose-dependent increase in mean arterial blood pressure of 8 ± 0.4, 19.3 ± 2.1, and 32 ± 2.4 mmHg, respectively. In contrast, the injection of a purified rabbit anti-rat angiotensinogen antibody (1.4 mg/kg) resulted in a significant decrease in mean arterial pressure (−33 ± 3.2 mmHg). Plasma angiotensinogen increased to 769 ± 32, 953 ± 42, and 1,289 ± 79 pmol/ml, respectively, after substrate and decreased by 361 ± 28 pmol/ml after antibody administration. Alterations in plasma angiotensinogen correlated well with changes in plasma renin activity. In summary, variations in circulating angiotensinogen can result in changes in blood pressure. In contrast to renin, which is known as a tonic regulator for the generation of ANG I, angiotensinogen may be a factor rather important for long-term control of the basal activity of the renin-angiotensin system.
Vascular function in alcohol-treated pregnant and nonpregnant mice
Authors: Cook Jocelynn L. , Zhang Yunlong , Davidge Sandra T.
Published: December 2017

The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was designed to determine the effect of alcohol consumption on nitric oxide-mediated vascular function in mice during pregnancy. Female pregnant or nonpregnant C57BL/6J mice were fed a control diet or a liquid diet of 25% ethanol-derived calories for 13 days (from gestational days 6–18). Phenylephrine vasoconstriction was blunted in pregnancy compared with the nonpregnant state due to enhanced nitric oxide modulation, which was impaired by ethanol exposure. Although the EC50 and maximal responses to methacholine were not different in nonpregnant vs. pregnant mice, the nitric oxide component to methacholine-induced vasorelaxation was greater in the pregnant mice. Interestingly, alcohol affected only the pregnant animals in their response to methacholine. These data indicate that alcohol reduced the nitric oxide modulation of vascular response, which was more pronounced during pregnancy. These studies provide novel information regarding the effects of alcohol on the maternal vascular system during pregnancy and thereby contribute to further understanding of the adverse effects associated with prenatal alcohol exposure.
A plastic interval timer synchronizes pubertal development of summer- and fall-born hamsters
Authors: Gorman Michael R.
Published: December 2017

Summer and fall decreases in day length induce reproductive regression in adult hamsters and delay reproductive maturation of their young. The following year pubertal development is triggered by an interval timer (IT) that renders animals refractory to inhibitory short day lengths after ∼25 wk. Timing of gonadal and somatic development was examined among offspring born to Siberian hamsters in early-August vs. late-September day lengths. Pubertal maturation was delayed in both groups until late winter. Gonadal growth occurred at significantly later ages among August- vs. September-born males as did late-winter spurts in ponderal growth of both sexes. Timing of reproductive and somatic development depended on postnatal rather than prenatal photoperiod exposure and was unrelated to the circadian entrainment status of dams. When developmental patterns were assessed in relation to time of year, group differences were largely eliminated. Because the IT triggers these developmental events, its duration must be plastic. This plasticity facilitates a relative synchronization or entrainment of developmental milestones in hamsters born into different late-summer/early-fall photoperiods.
Possible contribution of brain angiotensin III to ingestive behaviors in baboons
Authors: Blair-West J. R. , Carey K. D. , Denton D. A. , Madden L. J. , Weisinger R. S. , Shade R. E.
Published: December 2017

Recent experiments with specific aminopeptidase inhibitors in rats have strengthened earlier proposals that ANG III may be an important regulatory peptide in the brain. Central mechanisms regulating blood pressure, ingestive behaviors, and vasopressin release could be involved. Arguments in favor of a role for ANG III depend, in part, on the efficacy of ANG III as an agonist. These first studies in primates tested whether ANG III stimulates ingestive behaviors in baboons. Intracerebroventricular (ICV) infusions of ANG III were as potent as ANG II in stimulating water drinking and intake of NaCl solution. On the basis of this criterion and consistent with findings in rats, ANG III could be a main effector peptide in the regulation of ingestive behaviors in a primate.
Progression of heart failure after myocardial infarction in the rat
Authors: Francis J. , Weiss R. M. , Wei S. G. , Johnson A. K. , Felder R. B.
Published: December 2017

This study examined the early neurohumoral events in the progression of congestive heart failure (CHF) after myocardial infarction (MI) in rats. Immediately after MI was induced by coronary artery ligation, rats had severely depressed left ventricular systolic function and increased left ventricular end-diastolic volume (LVEDV). Both left ventricular function and the neurohumoral indicators of CHF underwent dynamic changes over the next 6 wk. LVEDV increased continuously over the study interval, whereas left ventricular stroke volume increased but reached a plateau at 4 wk. Plasma renin activity (PRA), arginine vasopressin, and atrial natriuretic factor all increased, but with differing time courses. PRA declined to a lower steady-state level by 4 wk. Six to 8 wk after MI, CHF rats had enhanced renal sympathetic nerve activity and blunted baroreflex regulation. These findings demonstrate that the early course of heart failure is characterized not by a simple “switching on” of neurohumoral drive, but rather by dynamic fluctuations in neurohumoral regulation that are linked to the process of left ventricular remodeling.
Maturation of baseline breathing and of hypercapnic and hypoxic ventilatory responses in newborn mice
Authors: Renolleau Sylvain , Dauger Stéphane , Autret Fanny , Vardon Guy , Gaultier Claude , Gallego Jorge
Published: December 2017

Breathing during the first postnatal hours has not been examined in mice, the preferred mammalian species for genetic studies. We used whole body plethysmography to measure ventilation (V˙e), breath duration (TTOT), and tidal volume (Vt) in mice delivered vaginally (VD) or by cesarean section (CS). In experiment 1, 101 VD and 100 CS pups aged 1, 6, 12, 24, or 48 h were exposed to 8% CO2or 10% O2for 90 s. In experiment 2, 31 VD pups aged 1, 12, or 24 h were exposed to 10% O2for 5 min. Baseline breathing maturation was delayed in CS pups, but V˙eresponses to hypercapnia and hypoxia were not significantly different between VD and CS pups [at postnatal age of 1 h (H1): 48 ± 44 and 18 ± 32%, respectively, in VD and CS pups combined]. TheV˙e increase induced by hypoxia was greater at H12 (46 ± 27%) because of TTOTresponse maturation. At all ages, hypoxic decline was ascribable mainly to a Vtdecrease, and posthypoxic decline was ascribable to a TTOTincrease with apneas, suggesting different underlying neuronal mechanisms.
Cold strain index applied to exercising men in cold-wet conditions
Authors: Castellani John W. , Young Andrew J. , O'Brien Catherine , Stulz Dean A. , Sawka Michael N. , Pandolf Kent B.
Published: December 2017

A cold strain index (CSI) based on rectal (Tre) and mean skin temperatures ([Formula: see text]sk) using data from seminude resting subjects has been proposed (Moran DS, Castellani JW, O'Brien C, Young AJ, and Pandolf KB. Am J Physiol Regulatory Integrative Comp Physiol 277: R556–R564, 1999). The current study determined whether CSI could provide meaningful data for clothed subjects exercising in the cold with compromised insulation. Ten men exercised in cold-wet conditions (CW) for 6 h before (D0) and after 3 days of exhaustive exercise (D3). Each hour of CW consisted of 10 min of standing in rain (5.4 cm/h, 5°C air) followed by 45 min of walking (1.34 m/s, 5.4 m/s wind, 5°C air). The change in Treacross time was greater ( P < 0.05) on D3 than on D0, and the change in [Formula: see text]skwas less ( P < 0.05) on D3 than on D0. Although CSI increased across time, the index at the end of both trials (D3 = 4.6 ± 0.6; D0 = 4.2 ± 0.8) was similar ( P > 0.05). Thus, while [Formula: see text]skwas 1.3°C higher ( P < 0.05) and Trewas 0.3°C lower ( P < 0.05) on D3 than on D0, CSI did not discriminate the greater heat loss that occurred on D3. These findings indicate that when vasoconstrictor responses to cold are altered, such as after exhaustive exercise, CSI does not adequately quantify the different physiological strain between treatments. CSI may be useful for indicating increased strain across time, but its utility as a marker of strain between different treatments or studies is uncertain because no independent measure of strain has been used to determine to what extent CSI is a valid and reliable measure of strain.
Substance P modulates nicotinic responses of intracardiac neurons to acetylcholine in the guinea pig
Authors: Zhang Lili , Tompkins John D. , Hancock John C. , Hoover Donald B.
Published: December 2017

—Application of substance P (SP) to intracardiac neurons of the guinea pig causes slow depolarization and increases neuronal excitability. The present study was done to determine the influence of SP on fast excitatory responses of intracardiac neurons to ACh. Intracellular recording methods were used to measure responses of intracardiac neurons in whole mount preparations of atrial ganglionated nerve plexus from guinea pig hearts. Local pressure ejection of 100 μM SP (1 s) from a glass micropipette caused slow depolarization of all neurons ( n = 38) and triggered action potential generation in 47% of the cells tested. Bath application of SP (0.5–100 μM) caused a dose-dependent depolarization of intracardiac neurons but rarely evoked action potentials, even at the highest concentration. However, such treatment with SP enhanced nicotinic responses evoked by local pressure ejections of ACh (10 mM, 10- to 100-ms duration) in 77% of intracardiac neurons studied ( n = 52). A significant increase in amplitude of ACh-evoked fast depolarization occurred during treatment with 0.5 μM SP (13.0 ± 1.8 mV for control vs. 17.7 ± 1.9 mV with SP present, n = 7, P = 0.019). At higher concentrations of SP, enhancement of the response to ACh resulted mainly in action potential generation. However, responses to ACh were attenuated by SP in 15% of the intracardiac neurons studied. This attenuation occurred primarily during exposure to 10 and 100 μM SP and was manifest as a reduction in amplitude of nicotinic fast depolarization or inhibition of ACh-evoked action potentials. These findings support the conclusion that SP could function as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig.
Afferent pathways for cardiac-somatic motor reflexes in rats
Authors: Jou C. Jerry , Farber Jay P. , Qin Chao , Foreman Robert D.
Published: December 2017

The present study used a rat model in which algogenic chemicals were infused into the pericardial sac to evoke spasmlike contractions in paraspinal muscles. The following techniques were used to study the roles of sympathetic (SCA) and vagal cardiac afferents (VCA) in electromyographic (EMG) responses to pericardial algogenic chemicals: chemical stimulation, electrical stimulation, and nerve transection. Activation with bradykinin ( n = 46) produced a significantly higher peak response than infusion of an algogenic mixture ( n = 53) containing chemicals that also activate VCA. Electrical stimulation of SCA produced bilateral EMG activities (7 of 7). Electrical stimulation of VCA did not evoke EMG activity but inhibited the chemically evoked EMG response (12 of 12). The chemically evoked response was decreased after transection of the left sympathetic chain ( n = 22) and was increased after bilateral vagotomy ( n = 19). These results suggest an excitatory and inhibitory role for SCA and VCA, respectively. Therefore, in addition to spinothalamic convergence of somatic and visceral afferents, activation of SCA to generate spasmlike muscle contractions could account in part for anginal pain, and VCA activation could attenuate this effect.
Weight loss in rats exposed to repeated acute restraint stress is independent of energy or leptin status
Authors: Harris Ruth B. S. , Mitchell Tiffany D. , Simpson Jacob , Redmann Stephen M. , Youngblood Bradley D. , Ryan Donna H.
Published: December 2017

Acute release of corticotropin-releasing factor (CRF) during repeated restraint (3-h restraint on each of 3 days) causes temporary hypophagia but chronic suppression of body weight in rats. Here we demonstrated that a second bout of repeated restraint caused additional weight loss, but continuing restraint daily for 10 days did not increase weight loss because the rats adapted to the stress. In these two studies serum leptin, which suppresses the endocrine response to stress, was reduced in restrained rats. Peripheral infusion of leptin before and during restraint did not prevent stress-induced weight loss, although stress-induced corticosterone release was suppressed. Restrained rats were hyperthermic during restraint, but there was no evidence that fever or elevated free interleukin-6 caused the sustained reduction in weight. Restraining food-restricted rats caused a small but significant weight loss. Food-restricted rats fed ad libitum after the end of restraint showed a blunted hyperphagia and slower rate of weight regain than their controls. These results indicate that repeated acute stress induces a chronic change in weight independent of stress-induced hypophagia and may represent a change in homeostasis initiated by repeated acute activation of the central CRF system.
Intersubject viability in growth hormone time course during different types of work
Authors: Raynaud J. , Capderou A. , Martineaud J. P. , Bordachar J. , Durand J.
Published: December 2017

This study addresses the question of variability of immunoreactive human growth hormone (IRHGH) response to the following types of muscular exercise. 1) One hour of submaximal exercise with restarting for 30 min after 20 min of recovery. Three types of responses were observed: a rise of [IRHGH] occurred in response to muscular activity; [IRHGH] was maintained at rest level during the first bout and then rose in the second bout; or [IRHGH] rose during the first bout and was no longer modified by the restarting. 2) Thirty minutes of heavy exercise. In some subjects [IRHGH] change was almost linear with time, reaching very high values and dropping as soon as exercise had stopped, whereas in others peak values were similar to those of submaximal exercise but, in contrast, plateaued during recovery. 3) One hour of exercise performed either continuously or with alternate sequences of 30-s exercise and 30-s pause. In intermittent exercise, some subjects displayed a similar time course of [IRHGH] as in continuous exercise and others displayed markedly high values. 4) One hour of submaximal exercise at three different intensities carried out at ambient temperatures of 24 and 33 degrees C. At 33 degrees C, in some subjects, [IRHGH] time course at the three intensities was unchanged at 33 degrees C compared with that at 24 degrees C, whereas the maximal value increased in another subject up to 150 ng X ml-1. A significant intrasubject consistency to a given type of exercise was evident over several months. The study emphasizes that caution should be used in drawing definite conclusions from averaged results with high variability.
Speed of low-frequency sound through lungs of normal men
Authors: Kraman S. S.
Published: December 2017

The speed of propagation of vesicular lung sound through the lung has not been clearly established. In a recent study (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 54: 304-308, 1983), Rice measured the speed of sound through the parenchyma of excised horse lungs and found it to be 25-70 m/s (less than 20% the speed of sound in air). Filling the lung with helium or sulfur hexafluoride changed the speed of transmission by less than 10%, indicating nongas propagation. The present study was designed to measure the speed of sound through human lungs in vivo. Five healthy, nonsmoking males (aged 27-38 yr) were studied. A microphone was placed on the neck beneath the larynx and another at each of eight locations on the chest wall. Measurements were made at functional residual capacity. White noise was band-pass filtered between 125 and 500 Hz, amplified, and delivered to a loudspeaker connected to a mouthpiece. The speed of sound was measured by cross-correlation analysis of the signals simultaneously detected by the tracheal and chest microphones. This was done after breathing both air and a mixture of 80% He in 20% O2 (He-O2). With air, the mean sound-transit time (trachea to chest wall) ranged from 2 ms at the upper chest to 5 ms at the lower chest (speed of approximately 30 m/s). With He-O2 the mean speed increased by only 10%, whereas the predicted increase of sound speed through gas alone would be greater than 100%. These results are consistent with the in vitro findings of Rice and suggest that within the frequency range of vesicular lung sounds transmission of sound introduced at the mouth is predominantly through the lung parenchyma, not through the airways.
Breathing pattern of kittens during hypoxia
Authors: Blanco C. E. , Hanson M. A. , Johnson P. , Rigatto H.
Published: December 2017

In 19 pentobarbital sodium-anesthetized kittens aged 5–34 days, inspired O2 was reduced from 21 to 6–512%. Respiratory frequency (f) and tidal volume (VT) increased within 30 s. Over 5 min f fell to about 60% below control; VT usually fell but remained above control. Arterial pressure fell in 80% of trials, sometimes before f fell. Arterial CO2 was below control, but raising inspired CO2 to keep expired CO2 at control did not prevent the fall in f and VT. The relation between VT and esophageal pressure or diaphragm electromyogram (EMG) did not change consistently, nor was the ratio of high to low frequencies in the diaphragm EMG altered. Carotid chemoreceptor discharge increased within 15 s, and at 5 min it was much above control. We conclude that the change in the breathing pattern in hypoxia is probably due to the activation of a central mechanism.
Physical fitness and cardiovascular response to lower body negative pressure
Authors: Raven P. B. , Rohm-Young D. , Blomqvist C. G.
Published: December 2017

Fourteen young male volunteers (mean age 28.1 yr) underwent maximal exercise performance testing and lower body negative pressure (LBNP) challenge to -50 Torr. Two distinct groups, fit (F, n = 8), mean maximal aerobic capacity (VO2max) = 70.2 +/- 2.6 (SE) ml O2 kg-1 X min-1, and average fit (AF, n = 6), mean VO2 max V 41.3 +/- 2.9 ml O2 kg-1 X min-1, P less than 0.001, were evaluated. Rebreathing CO2 cardiac outputs, heart rate (HR), blood pressure (BP), and leg circumference changes were monitored at each stage of progressive increases in LBNP to -50 Torr. The overall hemodynamic responses of both groups of subjects to LBNP were qualitatively similar to previous findings. There were no differences between F and AF in peripheral venous pooling as shown by a leg compliance (delta leg volume/delta LBNP) for the F of 12.6 +/- 1.1 and for the AF 11.6 +/- 2.0, P greater than 0.05. The F subjects had significantly less tachycardic response [delta HR/delta systolic BP of F = 0.7 beats/Torr] to LBNP to -50 Torr than the AF subjects [delta HR/delta systolic BP of unfit (UF) = 1.36 beats/Torr], P less than 0.05. In addition, overall calculated peripheral vascular resistance was significantly higher in the AF subjects (P less than 0.001), and there was a more marked decrease in systolic BP of the F subjects between the LBN pressures of -32 to -50 Torr. We concluded that the reflex response to central hypovolemia was altered by endurance exercise training.
Characterizing and correcting for the dynamic response of a bag-in-box system
Authors: Bates J. H. , Prisk G. K. , Tanner T. E. , McKinnon A. E.
Published: December 2017

A bag-in-box system (BBS) whose volume is monitored by a mechanical spirometer tends to have a slow response if the volume of the box is large, and this may significantly affect its measurement of gas flow. We describe a device for creating reproducible gas flows with which the impulse response of a BBS may be conveniently determined. Two computational techniques for correcting a BBS flow measurement for the effects of the impulse response were investigated: 1) an exponential model method that assumes a second-order model of the BBS dynamics and 2) a Fourier transform-based method of deconvolution known as Wiener filtering. Both correction methods produced a significant increase in the accuracy of BBS flow estimations, with the Wiener filter giving superior results.
Fructose utilization by lung
Authors: Das D. K. , Neogi A. , Steinberg H.
Published: December 2017

We have examined the role of fructose as a substrate for the mammalian lung. Isolated and ventilated rat lungs were perfused for 2 h in the presence of either [U-14C]- or [5-3H]fructose. Fructose utilization, 3H2O production, and lactate and pyruvate production were measured. Insulin had no effect on the production of radiolabeled lactate. The 14C label from [U-14C]fructose was incorporated into the neutral lipids, phospholipids, fatty acid moiety, and deacylated fraction of lung. The apparent Km and maximum velocity of enzyme reaction for fructose utilization were 0.5 mM and 75 nmol X h-1 X g dry wt-1, respectively. Recovery of fructose 1-phosphate and fructose 1,6-diphosphate after perfusion with fructose, as well as detection of fructokinase, aldolase, and triokinase activities in the lung homogenates, suggested that fructose had been metabolized via phosphorylation through fructose 1-phosphate. Activities of fructose-metabolizing enzymes were not altered by the induction of diabetes, hypophysectomy, or starvation. These results suggest that mammalian lungs may utilize fructose to synthesize fatty acids, which in turn are used for phospholipid biosynthesis. The utilization of fructose by lung does not seem to be affected by nutritional or hormonal conditions.
Effect of an exercise regimen on development of hypertension in rats
Authors: Fregly M. J.
Published: December 2017

The possibility that a forced exercise regimen might prevent the development of hypertension induced in rats both by renal encapsulation and chronic administration of deoxycorticosterone acetate (DOCA) and NaCl has been studied. In renal hypertensive rats, forced exercise at 0.4 to 1.25 miles/day, 7 days/wk for 16–22 wk failed to prevent the development of hypertension and cardiomegaly and reduced renal concentrating ability accompanying the hypertension. In DOCA-treated rats (10 mg/wk), forced exercise at 0.4 and 0.8 mile/day, 7 days/wk for 16 wk also failed to prevent both the development of hypertension and cardiomegaly. A review of data of others reveals that exercise may delay the development of hypertension in both Dahl salt-sensitive and spontaneously hypertensive (SHR) rats and may modestly reduce the maximal level of pressure attained. Of the four models of hypertension studied to date in rats, the Dahl salt-sensitive strain appears to be the one that responded best to exercise, although blood pressure eventually reached that of sedentary controls.
Hypoxia alters blood coagulation during acute decompression in humans
Authors: O'Brodovich H. M. , Andrew M. , Gray G. W. , Coates G.
Published: December 2017

Acute decompression is associated with a shortening of the activated partial thromboplastin time (aPTT). This study was performed to examine whether this change in aPTT results from hypoxia or hypobaria. We exposed healthy adults on three separate occasions to 2 h of 1) hypoxic hypobaria (410 Torr, n = 5), 2) hypoxic normobaria (fractional inspired O2 tension = 0.11, n = 4), or 3) normoxic hypobaria (410 Torr breathing supplemental O2, n = 5). The aPTT shortened during hypoxic hypobaria and hypoxic normobaria (P less than 0.05) but was unchanged during normoxic hypobaria. The prothrombin and thrombin times, hematocrit, and concentrations of fibrinogen, total plasma protein, and fibrinogen-fibrin fragment E were unchanged. During hypoxic hypobaria biologic levels of prekallikrein, high-molecular-weight kininogen, and factors XII, XI, X, VII, V, and II were unchanged, but procoagulant VIII (VIII:C) increased 50% without an increase in VIII-related antigen levels (VIIIR:Ag). Fibrin monomer was not detected in any group. In one subject who became ill after 1.5 h of hypoxic normobaria aPTT shortened by 10 s; the platelet count decreased by 93,000/mm3; VIII:C increased fivefold, but VIIIR:Ag only increased three-fold. We conclude that it is the hypoxia which shortens aPTT during acute decompression to 410 Torr and speculate that it results from an increase in plasma VIII:C-like activity.
Heat production during sleep
Authors: Shapiro C. M. , Goll C. C. , Cohen G. R. , Oswald I.
Published: December 2017

Heat production during sleep was studied by continuous indirect calorimetry with simultaneous electroencephalographic monitoring. Controlling for gross influences on heat production, comparisons of heat production during different sleep stages showed heat production in stage 4 sleep to be significantly lower than in other sleep stages. There appeared to be a gradation in heat production in non-rapid-eye-movement stages of sleep with stage 2 higher and stage 4 lower than stage 3. Heat production in stage 4 was less variable than in any other sleep stage. Both the level and variability of heat production was similar in stage 2 and rapid-eye-movement sleep. Heat production during the night was 9% lower than during resting wakefulness. The average heat production in stage 4 sleep was 14.4% lower than resting wakeful values.
Ventilatory CO2 responses during hypocapnia in anesthetized cats
Authors: Yamashiro S. M. , Ghazanshahi S.
Published: December 2017

CO2 response curves were measured in six anesthetized cats under open-loop conditions in both hyperoxia and hypoxia. Markedly nonlinear characteristics were observed with CO2 response slopes below the normal operating level almost three times that above the normal operating level. In all animals, complete apnea was observed when CO2 was reduced sufficiently. The zero ventilation intercept averaged 23.5 +/- 5.6 (SD) Torr in hyperoxia (arterial PO2 greater than 400 Torr) and 21.0 +/- 5.4 Torr in hypoxia (arterial PO2 = 52.7 Torr). These results suggest that an increased tendency for periodic breathing in hypocapnia could be due to the higher CO2 response slope.
Hormonal factors in reduced postprandial heat production of exercise-trained subjects
Authors: LeBlanc J. , Diamond P. , Cote J. , Labrie A.
Published: December 2017

The influence of exercise training on postprandial heat production was investigated in human subjects. Whereas resting metabolic rate was comparable for trained and nontrained subjects, the heat increment of feeding (HIF) after subjects consumed a meal containing 755 kcal was approximately 50% smaller in the trained subjects. Measurements of respiratory quotient also indicated a reduction of about 50% in glucose oxidation associated with exercise training. The levels of plasma norepinephrine increased significantly (P less than 0.01) from 200 to 300 pg/ml in the sedentary subjects, but the changes observed in trained subjects were not significant. During the early phase of the meal, plasma levels of insulin were increased, even before nutrients appeared in the blood. Throughout the study the enhanced sensitivity to insulin of the trained subjects was confirmed. the postprandial heat production was diminished in exercise-trained subjects, and it is suggested that this could be related to a reduced activity of the sympathetic nervous system. Another possibility is that this reduction in HIF is related to a facilitation of glucose disposal in the form of glycogen rather than in the form of lipids.
Persistent cardiomegaly induced by carbon monoxide and associated tachycardia
Authors: Penney D. G. , Stryker A. E. , Baylerian M. S.
Published: December 2017

To explore the effect of persistent cardiomegaly on cardiovascular function, groups of newborn rats inhaled up to 500 ppm CO for 33 days, after which development continued in ambient air. In the first two experiments hemodynamics were assessed by use of an anesthetized open-chest preparation; in the third experiment heart rate (HR) and arterial systolic blood pressure (BP) were monitored by auscultation in the conscious state. In all three experiments weights of left ventricle (LV) plus interventricular septum (S), both ventricles (2V), and right ventricle (RV) were significantly greater by prediction on the basis of body weight (BW) than for normal rats at 87–97, 166–176, and 337–339 days of age in females and 98–108, 177–183, and 337–339 days of age in males. 2V/BW ratio was significantly greater than littermate controls in all six instances. In all but one case (male, 177–183 days) the RV/(LV+S) weight ratios were significantly greater than the respective control groups. In experiments 1 and 2 unconscious HR was significantly elevated in females at 87–97 days and in males at 98–108 and 177–183 days. The first derivative of LV pressure rise was also increased. There was no significant change in BP or other hemodynamic parameters. In experiment 3 awake HR was elevated above controls in previously CO-treated males and females at six monitoring points between 78 and 200 days, whereas BP was not altered. BW of previously CO-exposed males was depressed and returned to normal only after 290 days. A similar decrement in BW was not seen in females. Neonatal CO inhalation and cardiomegaly causes persistent cardiomegaly and tachycardia, lasting a significant fraction of the maximal life span of the rat in both sexes.
Effects of pyridostigmine on ability of rats to work in the heat
Authors: Francesconi R. , Hubbard R. , Mager M.
Published: December 2017

Adult, male rats (300–325 g) were treated with pyridostigmine bromide (n = 22) or saline (n = 22) to quantitate the effects of cholinesterase inhibition (64%) on the ability to work (9.14 m/min, level treadmill) in the heat (35 degrees C). Pyridostigmine-treated rats had a mean endurance of 23 min, whereas saline-treated animals ran for nearly 35 min (P less than 0.001). Rates of rectal and skin temperature increments were significantly higher (P less than 0.001) in pyridostigmine-treated rats as were water losses (P less than 0.001). Exercise in the heat to hyperthermic exhaustion effected anticipated increments in circulating urea nitrogen, creatinine, lactate dehydrogenase, and potassium levels, whereas pyridostigmine pretreatment had additive effects on lactate and creatine kinase concentrations. Additionally, pyridostigmine elicited a significant (P less than 0.01) hyperglycemia before exercise, an effect noted also with other organophosphate simulants. We concluded that pyridostigmine-induced cholinesterase inhibition had a variety of debilitating effects during work in the heat.
Cholinergic and nonadrenergic mechanisms in human and guinea pig airways
Authors: Taylor S. M. , Pare P. D. , Schellenberg R. R.
Published: December 2017

Electrical field stimulation (70 V, 1 ms, 0.2–500 Hz) of human bronchial strips and guinea pig tracheal chains produced contractile and relaxant responses. Contractions were blocked by atropine, 10(-6) M, and tetrodotoxin (TTX), 0.1–1.0 micrograms/ml, demonstrating a cholinergic excitatory neural component. Frequencies causing half-maximal contractile response to field stimulation (EFc 50) were 10 +/- 2 Hz for guinea pig and 13 +/- 1 Hz for human airways. Relaxations were unmasked by atropine 10(-6) M and slightly diminished by propranolol in guinea pig but not human airways, demonstrating a predominantly nonadrenergic inhibitory pathway in both species. Relaxation of intrinsic tone occurred at stimulation frequencies of 1 Hz or more. Frequencies causing half-maximal relaxation (EFi 50) were 3.5 +/- 0.3 Hz for guinea pig trachealis and 38 +/- 6 Hz for human bronchi. Following 1 microgram/ml TTX, EFi 50 values increased to 104 +/- 12 and 70 +/- 14 Hz, respectively. Frequencies of field stimulation that were inhibitable by TTX (less than or equal to 20 Hz) induced greater relaxation in guinea pig than human airways (70 vs. 10% of the maximal relaxation to 10(-2) M theophylline, respectively). The methods of analysis outlined in this study can be used to compare relative degrees of functional innervation between tissues from the same or different species.
Interacting effects of hypoxia adaptation and acute hypercapnia on oxygen tolerance in rats
Authors: Clark J. M.
Published: December 2017

To define the effects of hypoxia adaptation on tolerance to a useful range of O2 pressures, groups of 20 or more rats were exposed to O2 at 1.0, 1.5, 2.0, 3.0, and 4.0 ATA before and after adaptation to an inspired PO2 (PIO2) of 71 Torr for 5 days. Effects of acute hypercapnia on O2 tolerance in hypoxia-adapted rats were also determined by exposing rats to the same O2 pressures with an inspired PCO2 (PICO2) of 60 Torr. In nonadapted rats exposed to O2 at 1.0, 1.5, 2.0, 3.0, and 4.0 ATA, 50% mortality (LD50) occurred at 76.4, 26.8, 17.4, 9.0, and 6.4 h, respectively. LD50 values in O2-CO2 at the same pressures were 77.1, 24.5, 15.6, 3.4, and 1.7 h. Hypoxia-adapted rats had only 20% mortality in O2 at 1.0 ATA, and survivors were killed at 336 h. In O2-CO2 at 1.0 ATA, mortality was 85% with an LD50 at 282 h. LD50 values in hypoxia-adapted rats at O2 pressures of 1.5, 2.0, 3.0, and 4.0 ATA were 63.1, 22.5, 7.9, and 3.8 h, respectively. Corresponding values in O2-CO2 were 29.5, 18.7, 4.9, and 1.9 h. Exposure to O2 at 4.0 ATA caused nearly immediate onset of violent convulsions in hypoxia-adapted rats compared with a 50% incidence of convulsions at 3.2 h in nonadapted rats. These data indicate that hypoxia-adaptation increases pulmonary O2 tolerance but reduces central nervous system (CNS) O2 tolerance. However, the enhanced pulmonary O2 tolerance in hypoxia-adapted rats is greatly diminished when acute hypercapnia is superimposed on O2 exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Sex differences in growth patterns of the airways and lung parenchyma in children
Authors: Pagtakhan R. D. , Bjelland J. C. , Landau L. I. , Loughlin G. , Kaltenborn W. , Seeley G. , Taussig L. M.
Published: December 2017

Seventeen boys and 19 girls, 8–15 yr in age, were studied to ascertain, in the two sex groups, the predictors of airway size [assessed by measurement of tracheal cross-sectional area (CSA) and maximal expiratory flows (Vmax)] and the relative rates of growth of the major divisions of the airways and lung parenchyma. In boys, total lung capacity (TLC) accounted for 77% of the variance of CSA and for 66% of the variability of Vmax. In contrast, somatic growth and maturation in girls accounted for only 45% of the variance of CSA and for 64% of the variability of Vmax; TLC was relatively unimportant. In boys, but not in girls, TLC-corrected CSA was significantly and inversely related to height and to TLC. In girls, TLC-corrected Vmax at 50 and 75% of forced vital capacity were directly related to height. These observations suggest different patterns of airway-parenchymal-somatic growth relationships in the two sexes. Furthermore, parenchymal growth appears to be the best determinant of airway growth in boys. In girls, other factors, perhaps genetic in nature, besides growth of parenchyma, may help determine airway size.
Naloxone reduces decrease in ventilation induced by hypoxia in newborn infants
Authors: De Boeck C. , Van Reempts P. , Rigatto H. , Chernick V.
Published: December 2017

The mechanism responsible for the decrease in ventilation during breathing of low fractional concentration of inspired O2 in the newborn infant is poorly understood. The present study tested the hypothesis that endogenous opiates account for this ventilatory decrease. Eleven healthy newborn infants breathed 15% O2, balance N2 for 5 min following an injection of saline and following an injection of naloxone. Neither injection caused a change in minute ventilation (VE) or ventilatory pattern when the infants were breathing room air. However, the decreased ventilation during hypoxia following naloxone was significantly less than that following saline. VE dropped about 14% following saline but only about 4% following naloxone. However, the adult ventilatory response to hypoxemia, i.e., a relatively sustained increase in VE, was not attained. Naloxone had no influence on the occurrence of periodic breathing during hypoxemia. Thus in the healthy full-term newborn infant, endogenous opiates account only for a part of the decreased ventilation during hypoxemia.
Breathing pattern in newborns
Authors: Mortola J. P.
Published: December 2017

Newborn mammals have a high O2 consumption (per unit body weight), which implies a high ventilation. The choice between an increase in volume, frequency, or both is probably dictated by energetic factors, including the likelihood of chest distortion with large inspirations. Data on ventilatory pattern of unanesthetized newborns of eight mammalian species, ranging in size from mice to infants, have been collected. Minute ventilation was linked to the O2 consumption and increased progressively less with the body weight of the species (BW0.86) due to a drop in frequency with size (BW-0.15), whereas tidal volume varied in proportion with body weight (BW1.01). Mean inspiratory flow per unit body weight was more than twice as large in newborn mice and rats than in piglets or infants, whereas the inspiratory time-to-total breath duration ratio was approximately constant among species, averaging 37%. During expiration occasional interruptions of the flow were observed in most newborns; measurements of esophageal pressure and diaphragmatic electromyogram pointed toward upper airways closure and not active breath holding as the explanation of this phenomenon.
Thermal adjustment to cold-water exposure in exercising men and women
Authors: McArdle W. D. , Magel J. R. , Spina R. J. , Gergley T. J. , Toner M. M.
Published: December 2017

Thermoregulatory responses were studied in 10 men and 8 women during 36-W exercise for 1 h in air and water at 20, 24, and 28 degrees C. Men were classified as high (27.6%; n = 2), average (16.8%; n = 4), and low (9.2%; n = 4) percent body fat, whereas women were classified as average (25.2%; n = 4) and low (18.5%; n = 4) fat. For both men and women, exercise of about 1.7 l O2 X min-1 was beneficial in either preventing or retarding the fall in rectal temperature (Tre) observed in a previous study for the same subjects at rest. The greatest thermal strain was noted for the leanest subjects. However, in no instance did exercise facilitate a drop in Tre compared with resting conditions. Despite a larger surface area-to-mass ratio (P less than 0.05) and less effective thermoregulation for women at rest compared with men, essentially similar thermoregulatory responses were observed for both sexes during exercise at each water temperature. For both the men and women, the thermoregulatory benefits of exercise were due largely to the added heat production from physical activity. For the female, an additional benefit of exercise may in part be derived from a more favorable distribution of subcutaneous fat over the active musculature.