bluuebunny/crossref_metadata_2025 huggingface dataset:
Hindlimb unloading induces a collagen isoform shift in the soleus muscle of the rat
Authors: Miller Todd A. , Lesniewski Lisa A. , Muller-Delp Judy M. , Majors Alana K. , Scalise Deb , Delp Michael D.
Published: December 2017

To determine whether hindlimb unloading (HU) alters the extracellular matrix of skeletal muscle, male Sprague-Dawley rats were subjected to 0 ( n = 11), 1 ( n= 11), 14 ( n = 13), or 28 ( n = 11) days of unloading. Remodeling of the soleus and plantaris muscles was examined biochemically for collagen abundance via measurement of hydroxyproline, and the percentage of cross-sectional area of collagen was determined histologically with picrosirius red staining. Total hydroxyproline content in the soleus and plantaris muscles was unaltered by HU at any time point. However, the relative proportions of type I collagen in the soleus muscle decreased relative to control (Con) with 14 and 28 days HU (Con 68 ± 5%; 14 days HU 53 ± 4%; 28 days HU 53 ± 7%). Correspondingly, type III collagen increased in soleus muscle with 14 and 28 days HU (Con 32 ± 5%; 14 days HU 47 ± 4%; 28 days HU 48 ± 7%). The proportion of type I muscle fibers in soleus muscle was diminished with HU (Con 96 ± 2%; 14 days HU 86 ± 1%; 28 days HU 83 ± 1%), and the proportion of hybrid type I/IIB fibers increased (Con 0%; 14 days HU 8 ± 2%; 28 days HU 14 ± 2%). HU had no effect on the proportion of type I and III collagen or muscle fiber composition in plantaris muscle. The data demonstrate that HU induces a shift in the relative proportion of collagen isoform (type I to III) in the antigravity soleus muscle, which occurs concomitantly with a slow-to-fast myofiber transformation.
Orexins/hypocretins excite rat sympathetic preganglionic neurons in vivo and in vitro
Authors: Antunes Vagner R. , Brailoiu G. Cristina , Kwok Ernest H. , Scruggs Phouangmala , Dun Nae J.
Published: December 2017

The two recently isolated hypothalamic peptides orexin A and orexin B, also known as hypocretin 1 and 2, are reported to be important signaling molecules in feeding and sleep/wakefulness. Orexin-containing neurons in the lateral hypothalamus project to numerous areas of the rat brain and spinal cord including the intermediolateral cell column (IML) of the thoracolumbar spinal cord. An in vivo and in vitro study was undertaken to evaluate the hypothesis that orexins, acting on sympathetic preganglionic neurons (SPNs) in the rat spinal cord, increase sympathetic outflow. First, orexin A (0.3, 1, and 10 nmol) by intrathecal injection increased mean arterial pressure (MAP) and heart rate (HR) by an average of 5, 18, and 30 mmHg and 10, 42, and 85 beats/min in urethane-anesthetized rats. Intrathecal injection of saline had no significant effects. Orexin B (3 nmol) by intrathecal administration increased MAP and HR by an average of 11 mmHg and 40 beats/min. The pressor effects of orexin A were attenuated by prior intrathecal injection of orexin A antibodies (1:500 dilution) but not by normal serum albumin. Intravenous administration of the α1-adrenergic receptor antagonist prazosin (0.5 mg/kg) or the β-adrenergic receptor antagonist propranolol (0.5 mg/kg) markedly diminished, respectively, the orexin A-induced increase of MAP and HR. Second, whole cell patch recordings were made from antidromically identified SPNs of spinal cord slices from 12- to 16-day-old rats. Superfusion of orexin A or orexin B (100 or 300 nM) excited 12 of 17 SPNs, as evidenced by a membrane depolarization and/or increase of neuronal discharges. Orexin A- or B-induced depolarizations persisted in TTX (0.5 μM)-containing Krebs solution, indicating that the peptide acted directly on SPNs. Results from our in vivo and in vitro studies together with the previous observation of the presence of orexin A-immunoreactive fibers in the IML suggest that orexins, when released within the IML, augment sympathetic outflow by acting directly on SPNs.
Genetic variation in photoperiodism among naturally photoperiodic rat strains
Authors: Lorincz Annaka M. , Shoemaker M. Benjamin , Heideman Paul D.
Published: December 2017

Rattus norvegicus has been considered nonphotoperiodic, but Fischer 344 (F344) rats are inhibited in growth and reproductive development by short photoperiod (SD). We tested photoresponsiveness of the genetically divergent Brown Norway (BN) strain of rats. Peripubertal males were tested in long photoperiod or SD, with or without 30% food reduction. Young males were photoresponsive, with reductions in testis size, body mass, and food intake in SD and with enhanced responses to SD when food restricted. Photoperiods ≤11 h of light inhibited reproductive maturation and somatic growth, whereas photoperiods of 12 h or more produced little or no response. F344/BN hybrids differ from both parent strains in the timing, amplitude, and critical photoperiod of photoperiodic responses, indicating genetic differences in photoperiodism between these strains. This is consistent with the hypothesis that ancestors of laboratory rats were genetically variable for photoperiodism and that different combinations of alleles for photoperiodism have been fixed in different strains of rats.
Splanchnic blood flow and hepatic glucose production in exercising humans: role of renin-angiotensin system
Authors: Bergeron Raynald , Kjær Michael , Simonsen Lene , Bülow Jens , Skovgaard Dorthe , Howlett Kirsten , Galbo Henrik
Published: December 2017

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O2consumption (V˙o2 max) followed by 30 min at 70% V˙o2 maxeither with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an ∼20-fold increase ( P < 0.001) in ANG II levels in the control group (5.4 ± 1.0 to 102.0 ± 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 ± 1.2 to 13.2 ± 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, V˙o2, and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 ± 0.12, ACE blockade; 1.59 ± 0.18 l/min, control) decreased during moderate exercise (0.78 ± 0.07, ACE blockade; 0.74 ± 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 ± 0.06, ACE blockade; 0.68 ± 0.10 mmol/min, control) increased during moderate exercise (1.97 ± 0.29, ACE blockade; 1.91 ± 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.
Disruption of the hypothalamic luteinizing hormone pulsing mechanism in aging men
Authors: Keenan Daniel M. , Veldhuis Johannes D.
Published: December 2017

The incremental nature of neuroendocrine aging suggests that subtle system dysregulation may precede overt axis failure. The present analyses unmask threefold disruption of pulsatile gonadotropin-releasing hormone (GnRH)-luteinizing hormone (LH) secretion in the aging male. First, by way of random effects-based deconvolution analysis, we document an elevated daily GnRH-LH pulse frequency in healthy older men [namely, mean (±SE) 23 ± 1 (older) vs. 15 ± 1 (young) LH secretory bursts/24 h, P < 0.001] and lower mean LH pulse mass [3.73 ± 0.58 (older) vs. 5.46 ± 0.66 (young) IU/l, P = 0.038]. However, total LH secretion rates and two-compartment LH elimination kinetics were comparable in the two age cohorts. Second, using the approximate entropy statistic, we show an equivalently random order-dependent succession of LH interpulse-interval lengths in young and older men, but a marked age-related deterioration of the ad seriatim regularity of LH pulse mass series in older individuals (P = 0.0057). Third, by modeling GnRH pulse-generator output as a Weibull renewal process (generalized Gamma density) to emulate loosely coupled GnRH neuronal oscillators, we identify an age-related reduction in the frequency-independent and order-independent variability of GnRH-LH interpulse-interval sets (P = 0.08). These findings indicate that the GnRH-LH pulsing mechanism in healthy older men maintains an increased mean frequency and lower amplitude of bursting activity, a reduced uniformity of serial LH pulse-mass values, and an impaired variability among interpulse-interval lengths. Thereby, the foregoing order-dependent and order-independent alterations in GnRH-LH signal generation in the aging human suggest a general framework for exploring subtle disruption of time-sensitive regulation of other neurointegrative systems.
Estrogen depletion induces NaCl-sensitive hypertension in female spontaneously hypertensive rats
Authors: Fang Zhiwu , Carlson Scott H. , Chen Y. F. , Oparil S. , Wyss J. Michael
Published: December 2017

In women, arterial pressure generally increases after menopause, but several studies suggest that women who eat large amounts of plant estrogens (phytoestrogens) experience a slower rise in the incidence of postmenopausal hypertension. This suggests that both ovarian hormones (principally estrogen) and phytoestrogens may protect at least some women from hypertension. The present study tests the hypothesis that phytoestrogens blunt hypertension in estrogen-depleted female spontaneously hypertensive rats (SHR). Three-week-old ovariectomized SHR were fed one of four diets that contained basal (0.6%) or high (8%) NaCl with or without dietary phytoestrogens for 9 wk. In SHR on the basal NaCl diet, arterial pressure was unaffected by the removal of dietary phytoestrogens. In contrast, in SHR on the high-NaCl diet, arterial pressure was significantly higher in rats on the phytoestrogen-free (204 ± 4 mmHg) compared with the phytoestrogen-replete (153 ± 4 mmHg) diet. Ganglionic blockade resulted in reductions in arterial pressure that were directly related to the dietary NaCl-induced increases in arterial pressure. Together, these data indicate that dietary phytoestrogens protect ovariectomized female SHR from dietary NaCl-sensitive hypertension and that the sympathetic nervous system plays an important role in this effect. Furthermore, these results demonstrate that dietary phytoestrogens can have a major impact on the interpretation of studies into the physiological role of estrogen in females.
Inhibition of placental 11β-hydroxysteroid dehydrogenase type 2 by catecholamines via α-adrenergic signaling
Authors: Sarkar Sumita , Tsai Shu-Whei , Nguyen Tien T. , Plevyak Michael , Padbury James F. , Rubin Lewis P.
Published: December 2017

The placenta expresses high levels of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) that converts cortisol into inactive 11-keto metabolites and effectively protects the developing fetus from maternal cortisol during pregnancy. Impairment of this glucocorticoid barrier has adverse effects on fetal outcomes. A similar spectrum of adverse fetal effects is induced by antenatal stress during pregnancy. To examine the hypothesis that physiological stress may regulate placental 11βHSD2 gene expression, we examined the effects of the catecholamines norepinephrine (NE) and epinephrine (E) on 11βHSD2 expression in human trophoblastic cells. With the use of Northern blotting and semiquantitative RT-PCR, we determined that NE and E rapidly downregulate 11βHSD2 steady-state mRNA levels in early- and late-gestation human trophoblasts and BeWo trophoblastic cells. Experiments using different adrenoceptor subtype-selective agonists and antagonists demonstrated that this catecholamine suppression of 11βHSD2 mRNA expression is mediated via both α1- and α2-adrenoceptors and is independent of β-adrenergic stimulation. To examine transcriptional regulation, BeWo cells were transiently transfected with a reporter construct in which an 11βHSD2 human promoter sequence was inserted upstream of the luciferase gene. Treatment with 10−7M NE decreased luciferase activity by ∼60% ( n = 3, P < 0.01). These results suggest the NE/E-mediated decrease in placental 11βHSD2 gene expression is an instance of α-adrenoceptor-specific rapid transcriptional inhibition of an adrenergic target gene. This molecular mechanism may be involved in the deleterious effects of antenatal physiological stress on fetoplacental growth and development.
Impact of pulsatility on the ensemble orderliness (approximate entropy) of neurohormone secretion
Authors: Veldhuis J. D. , Johnson M. L. , Veldhuis O. L. , Straume M. , Pincus S. M.
Published: December 2017

Regular patterns of neurohormone secretion are driven by underlying pulsatile and subordinate (feedback sensitive) dynamics. Measures of time-series orderliness, e.g., the approximate entropy (ApEn) statistic (Pincus SM. Proc Natl Acad Sci 88: 2297–2301, 1991), vividly discriminate pathological and physiological patterns of hormone release. To investigate how specific pulsatility features impact regularity estimates, we have examined the sensitivity of the ApEn metric to systematic variations in the frequency, amplitude, and half-life of simulated neurohormone pulse trains (Veldhuis JD, Carlson ML, and Johnson ML. Proc Natl Acad Sci 84: 7686–7690, 1987) and compared the impact of a high vs. low baseline luteinizing hormone (LH) pattern regularity state mimicking the normal female luteal phase and the young male, respectively. Shortening the interpulse interval length elevated ApEn in both pulsatility models, thereby signifying greater ensemble series irregularity. The frequency sensitivity of ApEn was robust to several complementary renditions of ApEn and to variations in experimental uncertainty, basal (nonpulsatile) LH secretion, and secretory burst amplitude. ApEn rose with increasing hormone half-life, especially in the face of low baseline variability emulated by midluteal LH secretion profiles. High variability of secretory burst amplitude, pulse duration, or interpeak intervals increased ApEn in the more orderly femalelike construct; in the highly irregular malelike LH pulse model, these variability changes had little effect on ApEn. In summary, the ensemble regularity statistic, ApEn, quantifies unequal pattern orderliness in neurohormone pulse trains with minimal dependence on mean pulse amplitude, interpulse baseline, or (subthreshold) sample uncertainty. Thus ApEn monitors changing secretory event frequency and interpulse variability with sensitivity to starting pattern regularity, providing a mechanistic linkage between model evolution and statistical change.
Physiological and pathological cardiac hypertrophy induce different molecular phenotypes in the rat
Authors: Iemitsu Motoyuki , Miyauchi Takashi , Maeda Seiji , Sakai Satoshi , Kobayashi Tsutomu , Fujii Nobuharu , Miyazaki Hitoshi , Matsuda Mitsuo , Yamaguchi Iwao
Published: December 2017

Pressure overload, such as hypertension, to the heart causes pathological cardiac hypertrophy, whereas chronic exercise causes physiological cardiac hypertrophy, which is defined as athletic heart. There are differences in cardiac properties between these two types of hypertrophy. We investigated whether mRNA expression of various cardiovascular regulating factors differs in rat hearts that are physiologically and pathologically hypertrophied, because we hypothesized that these two types of cardiac hypertrophy induce different molecular phenotypes. We used the spontaneously hypertensive rat (SHR group; 19 wk old) as a model of pathological hypertrophy and swim-trained rats (trained group; 19 wk old, swim training for 15 wk) as a model of physiological hypertrophy. We also used sedentary Wistar-Kyoto rats as the control group (19 wk old). Left ventricular mass index for body weight was significantly higher in SHR and trained groups than in the control group. Expression of brain natriuretic peptide, angiotensin-converting enzyme, and endothelin-1 mRNA in the heart was significantly higher in the SHR group than in control and trained groups. Expression of adrenomedullin mRNA in the heart was significantly lower in the trained group than in control and SHR groups. Expression of β1-adrenergic receptor mRNA in the heart was significantly higher in SHR and trained groups than in the control group. Expression of β1-adrenergic receptor kinase mRNA, which inhibits β1-adrenergic receptor activity, in the heart was markedly higher in the SHR group than in control and trained groups. We demonstrated for the first time that the manner of mRNA expression of various cardiovascular regulating factors in the heart differs between physiological and pathological cardiac hypertrophy.
Reduction in infarct size by local estrogen does not prevent autonomic dysfunction after stroke
Authors: Saleh Tarek M. , Cribb Alastair E. , Connell Barry J.
Published: December 2017

Systemic estrogen administration in male rats has been shown to normalize the autonomic dysfunction and reduce the infarct size after permanent middle cerebral artery occlusion (MCAO). Therefore, the present investigation determined if local microinjection of estrogen at the site of the infarct also promoted recovery of autonomic function and reduction of the infarct size. Experiments were done in anesthetized (thiobutabarbitol sodium; 100 mg/kg) male Sprague-Dawley rats instrumented to record baseline and reflex changes in cardiovascular and autonomic parameters. The right middle cerebral artery was permanently occluded using bipolar coagulation. Local microinjection of estrogen into the insular cortex before MCAO significantly reduced the infarct size but did not attenuate the MCAO-induced autonomic dysfunction. Injection of ICI-182,780 alone significantly increased infarct area; however, the greater infarct area was not associated with enhanced autonomic dysfunction. These results suggest that within the insula, endogenous estrogen activity can affect the extent of MCAO-induced cell death, but extracortical central nervous system sites may be responsible for mediating the beneficial effects of estrogen on the autonomic disturbances.
Expression and control of C-type natriuretic peptide in rat vascular smooth muscle cells
Authors: Woodard Geoffrey E. , Rosado Juan A. , Brown John
Published: December 2017

C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family mainly distributed in the central nervous system. CNP is also produced and secreted by the endothelium and inhibits vascular smooth muscle cell proliferation. We have reported that endothelial damage stimulates only transiently vascular smooth muscle cell proliferation in arteries due to the development of an autocrine neointimal system for CNP that modulates neointimal growth. The present study demonstrates the production and secretion of CNP in rat vascular smooth muscle cells in the absence of endothelium. In addition, these cells express atrial natriuretic peptide (ANP) and the natriuretic peptide receptors A, B, and C. The production and secretion of CNP in vascular smooth muscle cells is stimulated by transforming growth factor-β, whereas basic fibroblast growth factor plays an inhibitory role. These data show that ANP and mainly CNP are coexpressed with the natriuretic peptide receptors in rat vascular smooth muscle cells. This provides evidence for a vascular natriuretic peptide autocrine system of physiological relevance in these cells.
Endogenous angiotensin modulates PGE2-mediated release of substance P from renal mechanosensory nerve fibers
Authors: Kopp Ulla C. , Cicha Michael Z. , Smith Lori A.
Published: December 2017

Increasing renal pelvic pressure increases afferent renal nerve activity (ARNA) by a prostaglandin E2(PGE2)-mediated release of substance P (SP) from renal pelvic sensory nerves. We examined whether the ARNA responses were modulated by high- and low-sodium diets. Increasing renal pelvic pressure resulted in greater ARNA responses in rats fed a high-sodium than in those fed a low-sodium diet. In rats fed a low-sodium diet, increasing renal pelvic pressure 2.5 and 7.5 mmHg increased ARNA 2 ± 1 and 13 ± 1% before and 12 ± 1 and 22 ± 2% during renal pelvic perfusion with 0.44 mM losartan. In rats fed a high-sodium diet, similar increases in renal pelvic pressure increased ARNA 10 ± 1 and 23 ± 3% before and 1 ± 1 and 11 ± 2% during pelvic perfusion with 15 nM ANG II. The PGE2-mediated release of SP from renal pelvic nerves in vitro was enhanced in rats fed a high-sodium diet and suppressed in rats fed a low-sodium diet. The PGE2concentration required for SP release was 0.03, 0.14, and 3.5 μM in rats fed high-, normal-, and low-sodium diets. In rats fed a low-sodium diet, PGE2increased renal pelvic SP release from 5 ± 1 to 6 ± 1 pg/min without and from 12 ± 1 to 21 ± 2 pg/min with losartan in the incubation bath. Losartan had no effect on SP release in rats fed normal- and high-sodium diets. ANG II modulates the responsiveness of renal pelvic mechanosensory nerves by inhibiting PGE2-mediated SP release from renal pelvic nerve fibers.
Gender difference in the glucagon response to glucopenic stress in mice
Authors: Karlsson Sven , Scheurink Anton J. W. , Ahrén Bo
Published: December 2017

A gender difference in the glucagon response to insulin-induced hypoglycemia was previously demonstrated in humans. Whether this reflects a gender difference in autonomic activation or in pancreatic α-cell regulation is not known. We investigated the glucagon, epinephrine, and norepinephrine responses to neuroglycopenic stress induced by 2-deoxy-d-glucose (2-DG) or insulin in female and male mice. 2-DG increased plasma glucagon levels by 559 ± 68% in females versus 281 ± 46% in males ( P< 0.01). Plasma levels of epinephrine or norepinephrine after 2-DG administration did not differ between genders. During insulin-induced hypoglycemia, the glucagon response was similarly higher in females ( P < 0.001), whereas the plasma catecholamine response was higher in males ( P < 0.05). In vivo, the glucagon response to carbachol or clonidine was higher in females ( P < 0.05). In isolated islets, the glucagon response to carbachol (100 μM; P = 0.003) but not to clonidine (1 μM) was larger in females. We conclude that in addition to a larger α-cell mass (previously described in female mice), an increased sensitivity of the glucagon-producing α-cell to cholinergic activation contributes to the larger glucagon response to glucopenic stress in female mice.
Changes in NOS activity and protein expression during acute and prolonged ANG II administration
Authors: Moreno Carol , López Almudena , Llinás María T. , Rodríguez Francisca , López-Farré Antonio , Nava Eduardo , Salazar F. Javier
Published: December 2017

The aim of this study was to assess the effects of acute or prolonged increases of ANG II on nitric oxide synthase (NOS) activities and protein expression in mesenteric resistance vessels, left ventricle, renal cortex, and renal medulla. The response of NOS activities to ANG II is compared with that induced by phenylephrine. ANG II or phenylephrine were infused over either 3 h or 3 days to conscious rats. NOS activity was examined by measuring the rate of conversion ofl-[14C]arginine tol-[14C]citrulline. Protein levels of endothelial (e) and neuronal (n) NOS were determined by Western blot analysis. Arterial pressure (AP) increased ( P < 0.05) during acute and prolonged ANG II infusion. Ca2+-dependent NOS activity values (pmol of citrulline · min−1 · g wet wt−1) for control rats were 21 ± 9 in mesenteric arteries, 13 ± 7 in left ventricle, 14 ± 8 in renal cortex, and 411 ± 70 in renal medulla. Acute ANG II infusion increased ( P < 0.05) Ca2+-dependent NOS activity in renal cortex and renal medulla (81 ± 18 and 611 ± 48, respectively), but no differences were found in mesenteric arteries and left ventricle with respect to control rats. In contrast to the renal changes in NOS activity, acute ANG II infusion did not modify eNOS or nNOS expression in any of the tissues examined. Prolonged ANG II infusion increased ( P < 0.05) Ca2+-dependent NOS activity in mesenteric arteries (70 ± 17), renal cortex (104 ± 31), and left ventricle (49 ± 8) and did not elicit changes in renal medulla. After a prolonged ANG II infusion, eNOS and nNOS levels increased in all tissues examined with the exception of eNOS in the mesenteric arteries and nNOS in the left ventricle, which were not altered. Acute and prolonged phenylephrine infusion elevated AP to a similar extent as ANG II but only elicited significant increments of Ca2+-dependent NOS activity in renal cortex. These data indicate that acute and prolonged elevations in ANG II upregulate Ca2+-dependent NOS activity and protein expression in different tissues related to the control of blood pressure. However, these ANG II effects are heterogeneous with respect to the tissue implicated, the time course of the stimulation, and the NOS isoform involved. Phenylephrine only induces a significant elevation of Ca2+-dependent NOS activity in renal cortex.
Sympathetic nervous and hemodynamic responses to lower body negative pressure in hyperbaria in men
Authors: Yamauchi Katsuya , Tsutsui Yuka , Endo Yutaka , Sagawa Sueko , Yamazaki Fumio , Shiraki Keizo
Published: December 2017

The present study was designed to test the hypothesis that sympathetic nerve activity is attenuated in a hyperbaric environment. Response of muscle sympathetic nerve activity (MSNA) to central circulatory hypovolemic stress, lower body negative pressure (LBNP), was measured in nine men at normal and at 3 atm pressures. The stress consisted of 4 min each of control and LBNP at −20 and −40 mmHg. In addition to MSNA, heart rate, stroke volume (SV), forearm blood flow (FBF), and volume of the lower leg were recorded. A reduction of baseline HR occurred with increased forearm vascular resistance at 3 atm abs. The baseline MSNA decreased during hyperbaria. MSNA increased progressively with increasing LBNP in both atmospheric pressures, and the change from the baseline (ΔMSNA) was similar in both conditions. Changes in SV, FBF, and volume of the lower legs in response to LBNP were not statistically different during exposure to 2 atm pressures. The present study suggests that hyperbaria attenuates sympathetic nerve activity; however, its responsiveness to hypovolemic stress was not affected by hyperbaric exposure.
Involvement of trigeminal spinal nucleus in parasympathetic reflex vasodilatation in cat lower lip
Authors: Mizuta Kentaro , Kuchiiwa Satoshi , Saito Takashi , Mayanagi Hideaki , Karita Keishiro , Izumi Hiroshi
Published: December 2017

We examined whether the trigeminal spinal nucleus (Vsp) forms part of the central mechanism by which electrical stimulation of the central cut end of the lingual nerve (LN) evokes parasympathetic reflex vasodilatation in the lower lip in artificially ventilated, cervically vagosympathectomized cats deeply anesthetized with α-chloralose and urethane. For this purpose, we made microinjections within the brain stem to produce nonselective, reversible local anesthesia (lidocaine) or soma-selective, irreversible neurotoxic damage (kainic acid). Local anesthesia of Vsp by microinjection of lidocaine (2%; 1 μl/site) reversibly and significantly reduced the ipsilateral-LN-evoked parasympathetic reflex vasodilatation. Unilateral microinjection of kainic acid (10 mM/site; 1 μl) into Vsp ipsilateral to the stimulated LN led to an irreversible reduction in the reflex vasodilatation but had no effect on the vasodilatation elicited by stimulation of the contralateral LN. Such microinjection of kainic acid into Vsp had no effect on the vasodilatation evoked by electrical stimulation of the ipsilateral inferior salivatory nucleus. Electrical stimulation of Vsp elicited a blood flow increase in the lower lip in an intensity- and frequency-dependent manner, regardless of whether systemic arterial blood pressure rose or fell. Hexamethonium (1.0 mg/kg iv) significantly reduced the vasodilator responses elicited by electrical stimulation of the central cut end of LN or of Vsp, each to a similar degree. After hexamethonium, both vasodilator responses showed time-dependent recovery. These results strongly suggest that Vsp is an important bulbar relay for LN-evoked parasympathetic reflex vasodilatation in the cat lower lip.
Hypothalamic control of body temperature: insights from the past
Authors: Mack Gary W.
Published: December 2017

This essay looks at the historical significance of three APS classic papers that are freely available online:

Hammel HT, Hardy JD, and Fusco MM. Thermoregulatory responses to hypothalamic cooling in unanesthetized dogs. Am J Physiol 198: 481-486, 1960 ( http://ajplegacy.physiology.org/cgi/reprint/198/3/481 ).

Hammel HT, Jackson DC, Stolwijk JAJ, Hardy JD, and Strømme SB. Temperature regulation by hypothalamic proportional control with an adjustable set point. J Appl Physiol 18: 1146-1154, 1963 ( http://jap.physiology.org/cgi/reprint/18/6/1146 ).

Hellstrøm B and Hammel HT. Some characteristics of temperature regulation in the unanesthetized dog. Am J Physiol 213: 547-556, 1967 ( http://ajplegacy.physiology.org/cgi/reprint/213/2/547 ).
On the central pattern generator for the basic breathing rhythmicity
Authors: von Euler C.
Published: December 2017

Recent advances in several laboratories concerning the respiration-related medullary neurons, their locations, projections, interconnections, morphological and physiological properties, and patterns of inhibitory postsynaptic potentials, excitatory postsynaptic potentials, and discharge rate, on the one hand, and the “systems behavior,” on the other, have provided the basis for new hypothesis concerning the neural mechanisms underlying the central pattern generator (CPG) for breathing and its different parts. The onset of the “ramp”-like increase in inspiratory activity is due to an abrupt release of inhibition and a subsequent progressively increasing synaptic excitation of inspiratory premotor neurons. The integration of the excitatory “drive” inputs underlying the ramp inspiratory activity seems to depend on structures in the ventrorostral medulla, including nucleus paragigantocellularis. The termination of this activity by the off-switch mechanisms is actuated when a critical threshold is attained by the excitatory inputs of 1) a slowly increasing inspiration-related activity and 2) the afferent input from the pulmonary stretch receptors. The nature of the former activity is discussed. During the expiratory phase, an inhibitory activity suppresses inspiration-facilitating inputs with a slowly decaying power that controls the expiratory duration. The postinspiration activity, which brakes the rate of exhalation during the first part of the expiratory phase, depends on mechanisms separate from those responsible for the inspiratory ramp activity. The respiratory CPG seems to be organized with considerable amount of redundancy, or “degeneracity.”
Assessment of coagulation cascade during air microembolization of the lung
Authors: O'Brodovich H. , Andrew M. , Silver R. , Coates G.
Published: December 2017

Experiments were performed to determine whether activation of the coagulation cascade was required for pulmonary vascular permeability to increase during microembolization of the lung. For 30-45 min air microemboli were intravenously infused (0.05-0.10 ml X kg-1 X min-1) into awake sheep with chronic lung-lymph fistulas and anesthetized mongrel dogs. During embolization the pulmonary arterial pressure increased, and O2 partial pressure (PaO2) fell by more than 20 Torr (P less than 0.01). Subsequently lymph flow nearly tripled without a change in the lymph-to-plasma protein concentration ratio. Partial thromboplastin and prothrombin times, biological activity of antithrombin III, and circulating concentration of 125I-labeled dog or sheep fibrinogen did not change during or following air infusion. In two additional sheep an intravenous infusion of thrombin at 0.6 U X kg-1 X min-1 for 15 min resulted in a 20% decrease in 125I-labeled sheep fibrinogen concentration without a change in pulmonary arterial pressure or PaO2. We conclude that air microembolization can increase permeability to water and protein without a detectable activation of the coagulation cascade in the sheep or dog.
Effects of high-frequency breathing on pulmonary ventilation and gas exchange
Authors: Frostell C. , Pande J. N. , Hedenstierna G.
Published: December 2017

The effects of spontaneous high-frequency breathing (HFB) on lung function were evaluated in three subjects highly trained in the practice of yoga. Transpulmonary pressure was measured by an esophageal balloon catheter and gas flow by pneumotachography. The abdominal and rib cage contributions to tidal breathing were measured separately by respiratory inductive plethysmography. Gas exchange was studied by the conventional technique and by multiple inert gas elimination. During HFB, respiratory rate increased to 232 cycles/min with a tidal volume of 0.35 liter. This resulted in a more than 10-fold increase in expired minute ventilation to approximately 90 1/min. The transpulmonary pressure varied by 20 cmH2O, with the calculated elastic, resistive, and accelerative components varying by 2, 20, and 8 cmH2O, respectively. Respiratory work increased more than 200-fold in comparison with resting ventilation. A phase shift between thoracic and abdominal breathing was observed and was interpreted as a volume displacement of approximately 30 1/min between the two parts of the respiratory system. Arterial oxygen and carbon dioxide tension remained normal. Bohr dead space increased, while acetone dead space remained unaltered. A bimodal distribution of ventilation-perfusion ratios (VA/Q) was observed, with one mode in normal and another in “high” VA/Q regions.
High-frequency ventilation in lung edema: effects on gas exchange and perfusion
Authors: Breen P. H. , Ali J. , Wood L. D.
Published: December 2017

In six open-chest dogs, unilobar pulmonary edema was induced by injection of oleic acid into a lower lobe pulmonary arterial branch. Two hours later, intermittent positive-pressure ventilation (IPPV) and high-frequency oscillatory ventilation (HFOV) at matched mean alveolar pressures (MAP) were compared at 30-min intervals. The edematous lobar venous admixture (Qva/QT) increased by 0.14 (P less than 0.1) and its relative perfusion (QL/QT) decreased by 0.03. (P less than 0.1) during HFOV compared with IPPV. In another six dogs the MAP was increased by 1.5 cmH2O during HFOV; now the edematous lobar Qva/QT decreased by 0.15 (P less than 0.03) and QL/QT increased by 0.03 (P less than 0.03) during HFOV compared with IPPV. Greater MAP during HFOV also improved the edematous lobar ventilation (lobar venous PCO2) during HFOV compared with IPPV. Conceivably, the increase in MAP inflated collapsed, flooded regions, and thereby increased their O2 transfer, perfusion, and ventilation. Whole-lung Qva/QT was similar during IPPV and HFOV in both groups because of the opposing effects of lobar Qva/QT and QL/QT. We conclude that HFOV supports cardiovascular-respiratory function in open-chest unilobar pulmonary edema compared with IPPV at similar MAP; gas exchange and perfusion of edematous units may be sensitive to small changes in MAP, and we detected no intrinsic effects of HFOV on these variables. We speculate that similar beneficial effects in diffuse pulmonary edema may be effected by small variations in MAP during HFOV without the barotrauma side effects sometimes observed when MAP is increased during IPPV.
Tritiated water metabolism during dehydration and rehydration in the camel
Authors: Etzion Z. , Meyerstein N. , Yagil R.
Published: December 2017

The metabolism of tritiated water in the camel was compared in two 10-day periods, one when water was readily available and the second during dehydration. There was a radically depressed metabolism after 2 days of dehydration. Two other experiments examined the absorption rate of drinking water. In one experiment drinking water was labeled with tritium, and in the second experiment dilution of tritium-labeled blood was examined. In both experiments there was a rapid uptake and dilution of the blood, which continued for 4 h. Following this only slight changes were observed up to 24 h after drinking. The results are in accord with other data showing changes in erythrocyte shape 4 h after rapid rehydration. It is concluded that there is a rapid absorption of water in the rehydrating camel.
Muscle capillary supply and fiber type characteristics in weight and power lifters
Authors: Tesch P. A. , Thorsson A. , Kaiser P.
Published: December 2017

Muscle tissue samples were obtained from vastus lateralis muscle of elite weight/power lifters (WL/PL, n = 8), endurance athletes (EA, n = 8), and nonathletes (NA, n = 8). Histochemical stainings for myofibrillar ATPase, NADH-tetrazolium reductase, and amylase-periodic acid-Schiff, respectively, were undertaken to assess relative distribution of fast-twitch (FT) and slow-twitch (ST) muscle fiber types, fiber size, and capillary supply [capillaries per fiber (cap X fib-1) and capillaries per mm2 (cap X mm-2)]. Fiber type distribution in WL/PL, EA, and NA averaged 59 +/- 6 (SD), 40 +/- 11, and 61 +/- 10% FT. Values for mean fiber area and FT/ST area were significantly greater in WL/PL compared with values obtained in EA and NA. Similar values for cap X fib-1 were observed WL/PL (2.06 +/- 0.74) and NA (2.16 +/- 0.34). EA exhibited greater cap X fib-1 (3.11 +/- 0.73) than WL/PL (NS) and NA (P less than 0.01). However, cap X mm-2 in WL/PL (199 +/- 29) was lower than in EA (401 +/- 61, P less than 0.001) and NA (306 +/- 29, P less than 0.01). It is suggested that heavy resistance training in contrast to endurance training does not result in increased capillary density. Instead, as a consequence of fiber hypertrophy induced by muscle overloading, capillary density is decreased.
Comparison of motor unit activation during unilateral and bilateral leg extension
Authors: Vandervoort A. A. , Sale D. G. , Moroz J.
Published: December 2017

Possible differences between the extent of muscle utilization during leg extensions performed bilaterally (BL, both legs acting together) and unilaterally were investigated in young males in college. Significantly less integrated electromyographic activity was recorded from the quadriceps muscles of the dominant leg during BL compared with UL maximal voluntary contractions (MVC). BL strength was significantly lower than the summed (UL; sum of 2 legs acting singly) UL value under isometric conditions [BL = 91 +/- 2.5% (mean +/- SE) of UL; P less than 0.01, n = 9]. By use of a modified isokinetic dynamometer, it was also shown that the effect of increasing the velocity of concentric contraction was significantly greater (P less than 0.001) on BL than UL force development; thus at 424 degrees/s mean BL MVC was only 51 +/- 3.5% of UL. Greater resistance to fatigue was shown in the BL condition in repeated concentric contractions (% decline over 100 MVC at 105 degrees/s was 28 +/- 2.7% for BL vs. 38 +/- 2.9% for UL, P less than 0.001). Results indicated that the extent of motor unit activation appeared to be reduced in BL relative to UL MVC. Compatible evidence from the strength-velocity and fatigability comparisons suggested that this reduction was due to a lesser utilization of the fast-twitch fatigable type of motor unit.
Intramuscular fluid pressure during isometric contraction of human skeletal muscle
Authors: Sejersted O. M. , Hargens A. R. , Kardel K. R. , Blom P. , Jensen O. , Hermansen L.
Published: December 2017

Intramuscular fluid pressures were recorded in the vastus medialis of seven healthy male volunteers. Pressures were measured simultaneously at three different sites in the muscle by a catheter-tip transducer with extremely low volume-displacement characteristics and by two extracorporeal transducers connected to slit catheters. All three recording systems gave qualitatively similar results provided the catheters had inner diameters exceeding 0.53 mm and allowed measurement of pressures lasting as short as 1 s. Wick catheters yielded slower responses than slit catheters. At any position intramuscular fluid pressure increased linearly with force up to maximal voluntary contraction (MVC). However, slopes of these curves varied greatly mainly because the pressure was also a linear function of the distance from the fascia. The highest recorded pressure was 570 Torr. At prolonged submaximal contractions intramuscular fluid pressure oscillated independent of contraction force. The linearity of both the pressure-force relationship and the pressure-depth relationship is compatible with a simple model based on the law of Laplace because the muscle fibers are curved during contraction in this muscle. It is hypothesized that blood flow is first compromised deep in the muscle where pressure is highest and in general at lower stress or tension in short bulging muscles with great curvature of the fibers compared with long slender ones.
Effect of alveolar hypoxia on regional pulmonary perfusion
Authors: Neumann P. H. , Kivlen C. M. , Johnson A. , Minnear F. L. , Malik A. B.
Published: December 2017

We examined the effects of varying levels of alveolar hypoxia on regional distribution of pulmonary blood flow (QL) in control-ventilated sheep. Regional distribution of QL was measured using 15-micron-diam labeled microspheres during the base-line period and at two levels of hypoxemia (arterial O2 partial pressure 44 and 20 Torr). During the base-line period, regional distribution of QL in the prone position was uniform [14 +/- 4% (SE) of QL/g bloodless dry lung wt in the upper lung and 16 +/- 2% of QL/g in the dependent lung]. During hypoxemia, however, the regional distribution of QL increased in the upper lung (20 +/- 3% of QL/g) while it decreased in the dependent lung (10 +/- 2% of QL/g). The degree of flow distribution was proportional to the severity of hypoxemia. The flow distribution was not associated with significant increases in pulmonary blood flow (2.0 +/- 0.4----2.4 +/- 0.5----2.6 +/- 0.1 l/min) but was associated with increases in mean pulmonary arterial pressure (17.8 +/- 1.3----21.7 +/- 1.1----29.0 +/- 3.8 Torr). Therefore alveolar hypoxia results in a relative increase in regional pulmonary perfusion to the upper lung, which depends on the level of pulmonary hypertension. The increased upper lung perfusion may be due to recruitment in the upper lung or to vasodilation in this region.
Model analysis of gas distribution within human lung acinus
Authors: Paiva M. , Engel L. A.
Published: December 2017

Alveolar gas concentrations were simulated in an asymmetrically branching model of a human lung acinus based on morphometric measurements. The structure was expansile so that convective flow into and out of every part was proportional to its volume. Despite the homogeneous volume change solution of a differential equation for simultaneous convection and molecular diffusion following a 1-liter breath of O2 at 0.5 l/s predicted substantial inhomogeneity of O2 concentrations. This was reflected in a twofold range of inspired gas per unit volume computed from O2 concentrations averaged throughout expiration. Even a 10-s breath hold at end inspiration did not result in uniform concentrations. Larger breaths, corresponding to a ventilation of 60 l/min, increased the degree of inhomogeneity 50%. Diffusive pendelluft at intra-acinar branch points during expiration produced a sloping alveolar plateau of 0.53% N2/l, i.e., much smaller than that measured from the whole lung in vivo. Similarly, an estimate of single-breath mixing efficiency also indicated a much smaller degree of inhomogeneity than inferred from measurements of expired gases at the mouth. The model analysis suggests that if anatomical data used are representative of a normal lung, then the intra-acinar gas inhomogeneity, although substantial, constitutes a small fraction of the overall impairment in gas mixing.
Effects of immunization on cardiopulmonary alterations of gram-negative endotoxemia
Authors: Girotti M. J. , Menkes E. , MacDonald J. W. , Hong K. , Patterson A. , Todd T. R.
Published: December 2017

We studied the effects of an infusion of Serratia marcescens endotoxin on hemodynamic function, white blood cells, platelets, and the plasma levels of thromboxane B2 (TXB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) in awake monitored sheep. The animals were immunized using the core glycolipid (CGL) fraction of Escherichia coli J5 0111. An additional group of animals was studied after passive transfer of immune serum from the actively immunized CGL animals. Active immunization with CGL was effective in preventing the hematologic and hemodynamic changes as well as the elevations in TXB2 and 6-keto-PGF1 alpha seen during gram-negative endotoxemia. Passive immunization also reduced some of the deleterious effects of endotoxin infusion but was less effective than active immunization. This study demonstrates the potential of cross-specific immunization to protect against the cardiopulmonary alterations caused by gram-negative endotoxemia.
Effects of endurance exercise on metabolic water production and plasma volume
Authors: Pivarnik J. M. , Leeds E. M. , Wilkerson J. E.
Published: December 2017

Six endurance-trained and heat-acclimatized adult males ran for 1 h (or until exhaustion) at room temperature (23.8 degrees C) on three occasions. The work loads approximated 37, 56, and 74% of the subjects' aerobic capacities. Venous blood samples were drawn, and urine was collected before and immediately after each exercise bout. Metabolic cost was partitioned by energy substrate, and metabolic water production was quantified from urinary nitrogen, oxygen, and carbon dioxide production. Total body water loss was recorded as the decrease in body weight during the exercise. All subjects completed 1 h of exercise at the two lower exercise intensities but, due to exhaustion, averaged only 35.5 min at the highest work intensity. There were no significant changes in plasma volume after the exercise bouts. Metabolic water production increased with increasing work intensity as did the fraction of total caloric expenditure derived from carbohydrate metabolism. Plasma protein content significantly increased at all levels of exercise intensity. Metabolic water production alone would be of minimal help in plasma volume maintenance and thermoregulation during endurance exercise.
Aerobic parameters of exercise as a function of body size during growth in children
Authors: Cooper D. M. , Weiler-Ravell D. , Whipp B. J. , Wasserman K.
Published: December 2017

To examine the relationship between body weight in children and aerobic parameters of exercise, we determined the anaerobic threshold (AT), maximum O2 uptake (VO2max), work efficiency, and response time for O2 uptake (RT-VO2) in 109 healthy children (51 girls and 58 boys, range 6–17 yr old) using a cross-sectional study design. Gas exchange during exercise was measured breath by breath. The protocol consisted of cycle ergometry and a linearly increasing work rate (ramp) to the limit of the subject's tolerance. Both AT and VO2max increased systematically with body weight, whereas work efficiency and RT-VO2 were virtually independent of body size. The ratio of AT to VO2max decreased slightly with age, and its mean value was 60%. AT scaled to body weight to the power of 0.92, not significantly different from the power of 1.01 for VO2max. Thus both the AT and the VO2max increase in a highly ordered manner with increasing size, and as judged by AT/VO2max, the onset of anaerobic metabolism during exercise occurred at a relatively constant proportion of the overall limit of the gas transport system. We conclude that in children cardiorespiratory responses to exercise are regulated at optimized values despite overall change in body size during growth.