bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of gastric inhibitory properties of two secretin preparations
Authors: Mcilrath Donald C. , Hallenbeck George A.
Published: December 2017

Commercial preparations of secretin inhibit gastric secretion of Heidenhain pouches in response to certain stimuli. Since these preparations are mucosal extracts and not pure secretin, inhibition could be due to active materials other than secretin present in the extracts. To determine whether other active substances were present, two commercial secretin preparations, which were markedly different in weight per unit of pancreatic secretagogic activity, were tested for their relative abilities to stimulate pancreatic secretion in dogs with Thomas cannulas and to inhibit gastric secretion of Heidenhain pouches stimulated by exogenous gastrin in totally gastrectomized dogs. Inhibition of gastric secretion occurred with both preparations. The ratio between the weight of extract required to inhibit gastric secretion and that required to stimulate pancreatic secretion was the same for the two preparations despite the great differences in weights necessary to produce equivalent stimulation of the pancreas. This supports the concept that the same factor, either secretin or a closely related substance, accounted for both of these effects.
Effects of diet on HMP dehydrogenase and malic (TPN) dehydrogenase in the rat
Authors: Vaughan David A. , Winders Robert L.
Published: December 2017

The effects of several types of diets and feeding procedures on the activities of hexose monophosphate (HMP) dehydrogenase and malic (TPN) dehydrogenase were studied in rats. Inclusion of dietary fat at levels 15% or above depressed activity of both enzymes. Diets high in protein, and containing only 2% carbohydrate, depressed the activity of malic (TPN) dehydrogenase, but had no effect on HMP shunt dehydrogenase. Fat, fed concurrently with carbohydrate, depressed activity of both enzymes, but had little effect when fed on alternate days. Regeneration of HMP dehydrogenase activity after fasting was greatest during 75% protein + 17% alanine refeeding, followed in intensity by 90% protein, 75% protein + 17% glutamic acid, and least on an N-free high-carbohydrate diet. Malic (TPN) dehydrogenase, under these circumstances, was stimulated only by the N-free high-carbohydrate diet. Substitution of starch or dextrin for glucose in high-carbohydrate diets had a depressing effect on both of the enzymes studied.
Na and K activity coefficients in bile and bile salts determined by glass electrodes
Authors: Moore Edward W. , Dietschy John M.
Published: December 2017

Mathematical formulations for transmembrane potential differences are expressed in terms of ionic activities rather than ionic concentrations, and require knowledge of the activity coefficients of a given ionic species in mixed solutions. Cation-selective glass electrodes have been used to determine sodium and potassium activity coefficients in pure bile salt solutions and in native bile, relative to standard NaCl or KCl solutions. Comparison was made with osmotic coefficients determined by freezing-point depression. Both sodium and potassium activity coefficients in bile salt solutions and in bile were lower than those for NaCl or KCl solutions at corresponding concentrations, with potassium coefficients being lower than those for sodium. These derived activity coefficients have been used experimentally in in vivo and in vitro gall bladder preparations with close agreement between observed potentials and those predicted by the Hodgkin-Katz equation.
In vivo blood viscosity and hindrance
Authors: Olson Robert M.
Published: December 2017

This paper presents an in vivo method for measuring peripheral resistance and differentiating between the role of blood viscosity and hindrance. A vascular bed was connected to a pressure generator and recording system. At rest the vascular bed was perfused by the animal, but during the short duration of an experimental run the perfusing pressure was supplied solely by the pressure generator. The apparatus was constructed so that the flow rate was proportional to the rate of change of pressure. The shape of a portion of the curve of pressure versus time is determined solely by total resistance in the vascular bed. Total resistance is a function of hindrance and blood viscosity, and therefore a change in either of these produces a change in the shape of the pressure versus time curves. Since the change in shape produced by a change in viscosity differs from that produced by a change in hindrance, it is possible to differentiate between these two factors.
Dynamic relationship between sympathetic nerve activity and renal blood flow: a frequency domain approach
Authors: Guild Sarah-Jane , Austin Paul C. , Navakatikyan Michael , Ringwood John V. , Malpas Simon C.
Published: December 2017

Blood pressure displays an oscillation at 0.1 Hz in humans that is well established to be due to oscillations in sympathetic nerve activity (SNA). However, the mechanisms that control the strength or frequency of this oscillation are poorly understood. The aim of the present study was to define the dynamic relationship between SNA and the vasculature. The sympathetic nerves to the kidney were electrically stimulated in six pentobarbital-sodium anesthetized rabbits, and the renal blood flow response was recorded. A pseudo-random binary sequence (PRBS) was applied to the renal nerves, which contains equal spectral power at frequencies in the range of interest (<1 Hz). Transfer function analysis revealed a complex system composed of low-pass filter characteristics but also with regions of constant gain. A model was developed that accounted for this relationship composed of a 2 zero/4 pole transfer function. Although the position of the poles and zeros varied among animals, the model structure was consistent. We also found the time delay between the stimulus and the RBF responses to be consistent among animals (mean 672 ± 22 ms). We propose that the identification of the precise relationship between SNA and renal blood flow (RBF) is a fundamental and necessary step toward understanding the interaction between SNA and other physiological mediators of RBF.
Heat shock prevents simulated ischemia-induced apoptosis in renal tubular cells via a PKC-dependent mechanism
Authors: Meldrum K. K. , Meldrum D. R. , Sezen S. F. , Crone J. K. , Burnett A. L.
Published: December 2017

Heat shock produces cellular tolerance to a variety of adverse conditions; however, the protective effect of heat shock on renal cell ischemic injury remains unclear. Protein kinase C (PKC) has been implicated in the signaling mechanisms of acute preconditioning, yet it remains unknown whether PKC mediates heat shock-induced delayed preconditioning in renal cells. To study this, renal tubular cells (LLC-PK1) were exposed to thermal stress (43°C) for 1 h and heat shock protein (HSP) 72 induction was confirmed by Western blot analysis. Cells were subjected to simulated ischemia 24 h after thermal stress, and the effect of heat shock (delayed preconditioning) on ischemia-induced apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling) and B cell lymphoma 2 (Bcl2) expression (Western) was determined. Subsequently, the effect of PKC inhibition on HSP72 induction and heat stress-induced ischemic tolerance was evaluated. Thermal stress induced HSP72 production, increased Bcl2 expression, and prevented simulated ischemia-induced renal tubular cell apoptosis. PKC inhibition abolished thermal induction of HSP72 and prevented heat stress-induced ischemic tolerance. These data demonstrate that thermal stress protects renal tubular cells from simulated ischemia-induced apoptosis through a PKC-dependent mechanism.
The effect of alcohol consumption on the circadian control of human core body temperature is time dependent
Authors: Danel Thierry , Libersa Christian , Touitou Yvan
Published: December 2017

The few controlled studies dealing with the action of alcohol on core body temperature in humans have focused on the effect of a single dose of ethanol and reported that it has a hypothermic effect. No studies report the effects of repeated ethanol intake over a 24-h period, a pattern of consumption much closer to the clinical condition of chronic alcoholism. We therefore designed a trial in which alcohol was repeatedly and regularly administered, with a total dose of 256 g. Nine healthy male volunteers (mean age 23.3 ± 2.9 yr; range 21–30) each served as his own control. The circadian temperature rhythm was studied by a single-blind, randomized, crossover study that compared a 26-h alcohol session to a 26-h placebo session. The trial controlled for so-called masking effects known to affect temperature. The volunteers were in bed; the ambient temperature was maintained between 20 and 22°C. Meals were standardized. And light was controlled during the night. All sessions took place between November and April. The two sessions were separated by 2 to 5 wk. Rectal temperature was monitored every 20 min throughout the trial. We found the standard hypothermic effect of alcohol in the early hours of the trial, during the daytime, but our principal result is that alcohol consumption induced a very significant hyperthermic effect (+0.36°C) during the night and thereby reduced the circadian amplitude of core body temperature by 43%. The dramatic decrease of the amplitude of circadian temperature rhythm that we observed may explain, at least in part, some clinical signs observed in alcoholic patients, including sleep and mood disorders. We suggest that jet lag, shift work, and aging, which are known to alter body temperature, are aggravated by alcohol consumption.
2,3-Dinor-5,6-dihydro-15-F2t-isoprostane: a bioactive prostanoid metabolite
Authors: Hou X. , Roberts L. J. , Taber D. F. , Morrow J. D. , Kanai K. , Gobeil F. , Beauchamp M. H. , Bernier S. G. , Lepage G. , Varma D. R. , Chemtob S.
Published: December 2017

15-F2t-isoprostane (15-F2t-IsoP), also termed 8-isoprostaglandin F2α, is one of a series of prostanoids formed by free radical-mediated peroxidation of arachidonic acid and exerts potent biological actions such as vasoconstriction. We recently demonstrated that 15-F2t-IsoP is metabolized in humans to a major metabolite, 2,3-dinor-5,6-dihydro-15-F2t-IsoP (15-F2t-IsoP-M). 15-F2t-IsoP-M can also potentially be formed as a product of free radical-induced oxidation of the low abundance fatty acid γ-linolenic acid. We confirmed that 15-F2t-IsoP-M is generated during oxidation of γ-linolenic acid and explored whether it may exhibit biological activity. 15-F2t-IsoP-M caused marked constriction of porcine surface retinal and intraparenchymal brain microvessels, comparable to that observed with 15-F2t-IsoP. These effects were associated with increased thromboxane A2(TXA2) formation and were virtually abolished by TXA2-synthase and -receptor inhibitors (CGS-12970 and L-670596). Vasoconstriction induced by either 15-F2t-IsoP or 15-F2t-IsoP-M on perfused ocular choroid was also abrogated by TXA2-synthase inhibition as well as by removal of endothelium. Similar to 15-F2t-IsoP, 15-F2t-IsoP-M evoked vasoconstriction and TXA2generation by activating Ca2+influx from nonvoltage-gated channels (SK&F96365 sensitive) in the retina and from both nonvoltage- and N-type voltage-gated Ca2+channels (ω-conotoxin MVIIA sensitive), respectively, in brain endothelial and astroglial cells; smooth muscle cells were unresponsive to both agents. Cross-desensitization experiments further suggest that 15-F2t-IsoP and 15-F2t-IsoP-M act on the same receptor mechanism. Findings reveal a novel concept by which a β-oxidation metabolite of 15-F2t-IsoP that can also be formed by nonenzymatic oxidation of γ-linolenic acid is equivalently bioactive to 15-F2t-IsoP and may prolong the vascular actions of F2-IsoPs.
Increased blood pressure responses in neuropeptide Y transgenic rats
Authors: Michalkiewicz Mieczyslaw , Michalkiewicz Teresa , Kreulen David L. , McDougall Stuart J.
Published: December 2017

Considering the coexistence of neuropeptide Y (NPY) and norepinephrine in perivascular sympathetic nerves and the known vasoconstrictor cooperation of NPY with norepinephrine, we investigated the involvement of NPY in long-term control of cardiovascular functions using NPY transgenic (NPY-tg) rats. These rats were developed by injection of the rat (Sprague-Dawley) pronuclei with a 14.5-kb clone of the rat structural NPY gene. When compared with nontransgenic littermates, NPY concentrations were significantly increased in a number of cardiovascular tissues of NPY-tg hemizygotes. Direct basal mean arterial pressure and heart rate were not changed, but calculated total vascular resistance was significantly increased in NPY-tg subjects. Arterial pressure increases, in response to norepinephrine injection, were greater in the NPY-tg rats. Also, the hypotension and bradycardia in response to hemorrhage were significantly reduced in NPY-tg subjects. These results indicate that NPY, when expressed in increased amounts, potentiates the pressor effects of norepinephrine and contributes to maintaining blood pressure during hemorrhage, but it does not alter resting blood pressure. These transgenic rats will facilitate studies of the role of NPY signaling in cardiovascular regulation, particularly regarding its functional cooperation with norepinephrine.
Muscle angiogenic growth factor gene responses to exercise in chronic renal failure
Authors: Wagner Peter D. , Masanés Ferran , Wagner Harrieth , Sala Ernest , Miró Oscar , Campistol J. M. , Marrades Ramon M. , Casademont Jordi , Torregrosa V. , Roca Josep
Published: December 2017

Patients with chronic renal failure (CRF) have impaired exercise capacity even after erythropoietin treatment. We recently showed that although this is explained in part by reduced convective O2 delivery to muscles, there is also an impairment of O2 transport from muscle capillaries to the mitochondria. Given the importance of the capillary surface area for capillary mitochondrial O2 transport and reports of reduced capillarity in CRF, we hypothesized that the angiogenic gene response to exercise is impaired in such patients. Six patients with CRF and six control subjects matched for age, size, and sedentary lifestyle exercised on a single occasion for 1 h at similar work intensities averaging 50% of maximal capacity. Exercise was confined to the knee extensors of a single leg by means of a specially designed leg-kick ergometer. A percutaneous biopsy of the quadriceps was taken within 30 min of cessation of exercise and compared with a similar biopsy done at different times without any prior exercise for 24 h. Conventional Northern blots were prepared and probed for vascular endothelial growth factor (VEGF; the major putative angiogenic growth factor for muscle), basic fibroblast growth factor (bFGF), and transforming growth factor (TGF)-β1. Data during both rest and exercise were successfully obtained in four subjects of each group. We also assessed muscle capillarity and mitochondrial oxidative capacity to relate to these changes. Mitochondrial oxidative capacity was normal, whereas capillary number per fiber was 12% lower than in normal subjects. VEGF mRNA abundance was increased after exercise by about one order of magnitude, with no reduction in response in CRF. For bFGF and TGF-β1, exercise elicited no response in either group. Reduced muscle capillarity in CRF does not, therefore, stem from reduced transcription of VEGF. To the extent that VEGF is important to exercise-induced angiogenesis in muscle, we suspect a posttranscriptional aberration in this response occurs in CRF to explain reduced capillarity.
Dexamethasone and epinephrine stimulate surfactant secretion in type II cells of embryonic chickens
Authors: Sullivan Lucy C. , Orgeig Sandra
Published: December 2017

Pulmonary surfactant (PS), a mixture of phospholipids and proteins secreted by alveolar type II cells, functions to reduce the surface tension in the lungs of all air-breathing vertebrates. Here we examine the control of PS during lung development in a homeothermic egg-laying vertebrate. In mammals, glucocorticoids and autonomic neurotransmitters contribute to the maturation of the surfactant system. We examined whether dexamethasone, epinephrine, and carbamylcholine hydrochloride (agonist for acetylcholine) increased the amount of PS secreted from cultured type II cells of the developing chicken lung. In particular, we wanted to establish whether dexamethasone would increase PS secretion through a process involving lung fibroblasts. We isolated and cocultured type II cells and lung fibroblasts from chickens after 16, 18, and 20 days of incubation and from hatchlings ( day 21). Epinephrine stimulated phosphatidylcholine (PC) secretion at all stages, whereas dexamethasone stimulated secretion of PC at days 16 and 18. Carbamylcholine hydrochloride had no effect at any stage. This is the first study to establish the existence of similar cellular pathways regulating the development of surfactant in chickens and eutherian mammals, despite the vastly different birthing strategies and lung structure and function.
Abrogation of α-adrenergic vasoactivity in chronically inflamed rat knee joints
Authors: McDougall Jason J.
Published: December 2017

It has previously been shown that chronic inflammation causes a reduction in sympathetic nerve-mediated vasoconstriction in rat knees. To determine whether this phenomenon is due to an alteration in smooth muscle adrenoceptor function, the present study compared the α-adrenoceptor profile of blood vessels supplying the anteromedial capsule of normal and chronically inflamed rat knee joints. While the rats were under urethan anesthesia, the α1-adrenoceptor agonists methoxamine and phenylephrine and the α2-adrenoceptor agonist clonidine (0.1-ml bolus; dose range 10−12-10−7mol) were applied to exposed normal rat knees, resulting in a dose-dependent fall in capsular perfusion. Comparison of drug potencies indicated that α2-adrenergic effects > α1-vasoactivity. One week after intra-articular injection of Freund's complete adjuvant to induce chronic joint inflammation, the vasoconstrictor effects of methoxamine, phenylephrine, and clonidine were all significantly attenuated compared with normal controls. These findings show that the preponderance of sympathetic adrenergic vasoconstriction in the anteromedial capsule of the rat is carried out by postjunctional α2-adrenoceptors. Chronic joint inflammation compromises α1- and α2-adrenoceptor function, and this change in α-adrenergic responsiveness may help explain the perfusion changes commonly associated with inflammatory arthritis.
Neuronal application of capsaicin modulates somatic pressor reflexes
Authors: LeDoux J. F. , Wilson L. B.
Published: December 2017

Static contraction of skeletal muscle elicits a reflex increase in cardiovascular function. Likewise, noxious stimuli activate somatic nociceptors eliciting a reflex increase in cardiovascular function. On the basis of recent work involving spinothalamic cells in the dorsal horn, we hypothesized that the dorsal horn cells involved in the aforementioned reflexes would be sensitized by applying capsaicin (Cap) to a peripheral nerve. If correct, then Cap would enhance the cardiovascular increases that occur when these reflexes are evoked. Cats were anesthetized, and the popliteal fossa was exposed. Static contraction was induced by electrical stimulation of the tibial nerve at an intensity that did not directly activate small-diameter muscle afferent fibers, whereas nociceptors were stimulated by high-intensity stimulation (after muscle paralysis) of either the saphenous nerve (cutaneous nociceptors) or a muscular branch of the tibial nerve (muscle nociceptors). The reflex cardiovascular responses to these perturbations (contraction or nociceptor stimulation) were determined before and after direct application of Cap (3%) onto the common peroneal nerve, using a separate group of cats for each reflex. Compared with control, application of Cap attenuated the peak change in mean arterial pressure (MAP) evoked by static contraction (ΔMAP in mmHg: 38 ± 10 before and 24 ± 8 after ipsilateral Cap; 47 ± 10 before and 33 ± 10 after contralateral Cap). On the other hand, Cap increased the peak change in MAP evoked by stimulation of the saphenous nerve from 57 ± 8 to 77 ± 9 mmHg, as well as the peak change in MAP elicited by activation of muscle nociceptors (36 ± 9 vs. 56 ± 14 mmHg). These results show that the reflex cardiovascular increases evoked by static muscle contraction and noxious input are differentially affected by Cap application to the common peroneal nerve. We hypothesize that a Cap-induced alteration in dorsal horn processing is the locus for this divergent effect on these reflexes.
The influence of topical capsaicin on the local thermal control of skin blood flow in humans
Authors: Stephens Dan P. , Charkoudian Nisha , Benevento Jessica M. , Johnson John M. , Saumet Jean Louis
Published: December 2017

To test whether heat-sensitive receptors participate in the cutaneous vascular responses to direct heating, we monitored skin blood flow (SkBF; laser Doppler flowmetry) where the sensation of heat was induced either by local warming (TLoc; Peltier cooling/heating unit) or by both direct warming and chemical stimulation of heat-sensitive nociceptors (capsaicin). In part I, topical capsaicin (0.075 or 0.025%) was applied to 12 cm2 of skin 1 h before stepwise local warming of untreated and capsaicin-treated forearm skin. Pretreatment with 0.075% capsaicin cream shifted the SkBF/TLoc relationship to lower temperatures by an average of 6 ± 0.8°C ( P < 0.05). In part II, we used a combination of topical capsaicin (0.025%) and local warming to evoke thermal sensation at one site and only local warming to evoke thermal sensation at a separate site. Cutaneous vasomotor responses were compared when the temperatures at these two sites were perceived to be the same. SkBF differed significantly between capsaicin and control sites when compared on the basis of actual temperatures, but that difference became insignificant when compared on the basis of the perceived temperatures. These data suggest heat-sensitive nociceptors are important in the cutaneous vasodilator response to local skin warming.
Acute G-CSF therapy is not protective during lethalE. colisepsis
Authors: Quezado Zenaide , Parent Chantal , Karzai Waheedullah , Depietro Michael , Natanson Charles , Hammond William , Danner Robert L. , Cui Xizhong , Fitz Yvonne , Banks Steven M. , Gerstenberger Eric , Eichacker Peter Q.
Published: December 2017

We investigated whether decreases in circulating polymorphonuclear neutrophils (PMN) during lethal Escherichia coli ( E. coli) sepsis in canines are related to insufficient host granulocyte colony-stimulating factor (G-CSF). Two-year-old purpose-bred beagles had intraperitoneal E. coli-infected or -noninfected fibrin clots surgically placed. By 10 to 12 h following clot, both infected survivors and nonsurvivors had marked increases ( P = 0.001) in serum G-CSF levels (mean peak G-CSF ng/ml ± SE, 1,931 ± 364 and 2,779 ± 681, respectively) compared with noninfected controls (134 ± 79), which decreased at 24 to 48 h. Despite increases in G-CSF, infected clot placement caused delayed ( P = 0.06) increases in PMN (mean ± SE change from baseline in cells × 103/mm3at 24 and 48 h) in survivors (+3.9 ± 3.9 and +13.8 ± 3.6) compared with noninfected controls (+13.1 ± 2.8 and +9.1 ± 2.5). Furthermore, infected nonsurvivors had decreases in PMN (−1.4 ± 1.0 and −1.1 ± 2.3, P = 0.006 compared with the other groups). We next investigated whether administration of G-CSF immediately after clot placement and continued for 96 h to produce more rapid and prolonged high levels of G-CSF after infection would alter PMN levels. Although G-CSF caused large increases in PMN compared with control protein from 2 to 48 h following clot in noninfected controls, it caused much smaller increases in infected survivors and decreases in infected nonsurvivors ( P = 0.03 for the ordered effect of G-CSF comparing the three groups). Thus insufficient host G-CSF is unlikely the cause of decreased circulating PMN in this canine model of sepsis. Other factors associated with sepsis either alone or in combination with G-CSF itself may reduce increases or cause decreases in circulating PMN.
Cardiovascular changes induced by central hypertonic saline are accompanied by glutamate release in awake rats
Authors: Jin Qing-Hua , Ueda Yuto , Ishizuka Yuta , Kunitake Takato , Kannan Hiroshi
Published: December 2017

To elucidate neurochemical mechanisms responsible for cardiovascular responses induced by central salt loading, we directly perfused the paraventricular nucleus (PVN) of the hypothalamus region with hypertonic saline (0.3 or 0.45 M) by using an in vivo brain microdialysis technique. We then measured the extracellular concentrations of glutamate in the PVN region in conscious rats along with the blood pressure and heart rate. Blood pressure, heart rate, and glutamate levels were increased by perfusion of 0.45 M saline; however, they did not change by perfusion of 0.3 M saline. Next, we examined the possible involvement of glutamate in the cardiovascular responses induced by hypertonic saline. Dizocilpine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, attenuated the increases of blood pressure and heart rate, although 6-cyano-7-nitroquinoxaline-2,3-dione, an antagonist of the non-NMDA receptor, did not affect the blood pressure and heart rate. Our results show that local perfusion of the hypothalamic PVN region with hypertonic saline elicits a local release of glutamate, which may act via NMDA-type glutamate receptors to produce cardiovascular responses.
Attenuation of inhibitory effect of CNP on the secretion of ANP from hypertrophied atria
Authors: Kim Suhn Hee , Han Jeong Hee , Lim Sung Hee , Lee Sook Jeong , Kim Sung Zoo , Cho Kyung Woo
Published: December 2017

It has been shown that atrial natriuretic peptide (ANP) influences proliferation of cardiac cells. To define the possible role of C-type natriuretic peptide (CNP) in cardiac hypertrophy, the influence of CNP on the secretion of ANP was studied with the use of perfused nonbeating atria from monocrotaline-treated rats. Increases in atrial volume caused proportional increases in ANP secretion that were markedly suppressed by CNP (10−6 M) in nonhypertrophied left atria and control right atria but not in hypertrophied right atria. However, increases in atrial volume and mechanically stimulated extracellular fluid (ECF) translocation by CNP were similar to those in the control group. Therefore, the secretion of ANP in terms of ECF translocation was decreased by CNP in nonhypertrophied left and control right atria but not in hypertrophied atria. However, the inhibitory effect of 8-bromo-cGMP on the secretion of ANP was observed in both atria. The cGMP productions from perfused hypertrophied atria and their membranes exposed to CNP were significantly lower than those from nonhypertrophied atria. No significant difference in natriuretic peptide receptor-B transcript was found. Therefore, attenuation of the inhibitory effect of CNP on the ANP secretion in hypertrophied atria may be due to lack of cGMP production. The results showing the relief of CNP-induced negative inhibition of ANP secretion by atrial hypertrophy suggest that CNP may be a contributing factor to delay the development of cardiac hypertrophy.
Differential chemoreceptor reflex responses of adrenal preganglionic neurons
Authors: Cao Wei-Hua , Morrison Shaun F.
Published: December 2017

Adrenal sympathetic preganglionic neurons (ADR SPNs) regulating the chromaffin cell release of epinephrine (Epi ADR SPNs) and those controlling norepinephrine (NE ADR SPNs) secretion have been distinguished on the basis of their responses to stimulation in the rostral ventrolateral medulla, to glucopenia produced by 2-deoxyglucose, and to activation of the baroreceptor reflex. In this study, we examined the effects of arterial chemoreceptor reflex activation, produced by inhalation of 100% N2 or intravenous injection of sodium cyanide, on these two groups of ADR SPNs, identified antidromically in urethane-anesthetized, artificially ventilated rats. The mean spontaneous discharge rates of 38 NE ADR SPNs and 51 Epi ADR SPNs were 4.4 ± 0.4 and 5.6 ± 0.4 spikes/s at mean arterial pressures of 98 ± 3 and 97 ± 3 mmHg, respectively. Ventilation with 100% N2 for 10 s markedly excited all NE ADR SPNs (+222 ± 23% control, n = 36). In contrast, the majority (40/48; 83%) of Epi ADR SPNs were unaffected or slightly inhibited by ventilation with 100% N2 (population response: +6 ± 10% control, n = 48). Similar results were obtained after injection of sodium cyanide. These observations suggest that the network controlling the spontaneous discharge of NE ADR SPNs is more sensitive to brief arterial chemoreceptor reflex activation than is that regulating the activity of Epi ADR SPNs. The differential responsiveness to activation of the arterial chemoreceptor reflex of the populations of ADR SPNs regulating epinephrine and norepinephrine secretion suggests that their primary excitatory inputs arise from separate populations of sympathetic premotor neurons and that a fall in arterial oxygen tension is not a major stimulus for reflex-mediated adrenal epinephrine secretion.
Hypotensive and sedative effects of clonidine injected into the rostral ventrolateral medulla of conscious rats
Authors: Yamazato Masanobu , Sakima Atsushi , Nakazato Jun , Sesoko Shogo , Muratani Hiromi , Fukiyama Koshiro
Published: December 2017

We examined the effects of clonidine injected unilaterally into the rostral ventrolateral medulla (RVLM) of conscious, unrestrained rats. We also examined whether the local α2-adrenoceptor mechanism contributed to the action of clonidine injected into the RVLM. Injection of clonidine but not vehicle solution significantly decreased the mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious, unrestrained rats as well as in propofol-anesthetized rats. The frequency of natural behavior was significantly lower after clonidine injection than after vehicle injection. The depressor and sympathoinhibitory responses were significantly larger in the propofol-anesthetized rats than in the conscious rats. Coinjection of a selective α2-adrenoceptor antagonist, 2-methoxyidazoxan, with clonidine into the RVLM significantly attenuated the depressor, bradycardiac, sympathoinhibitory, and sedative effects of clonidine injected alone. In conclusion, clonidine injected into the RVLM decreased MAP, HR, and RSNA and caused sedation in conscious, unrestrained rats. The action of clonidine in the RVLM was at least partly mediated by α2-adrenoceptor mechanisms.
Hypothalamic dopaminergic receptor expressions in anorexia of tumor-bearing rats
Authors: Sato Tomoi , Meguid Michael M. , Fetissov Sergueï O. , Chen Chung , Zhang Lihua
Published: December 2017

Our past microdialysis studies in ventromedial hypothalamic nucleus (VMN) and lateral hypothalamic area (LHA) of changes in dopamine concentrations in response to changes in food intake [characterized as feeding pattern (changes in meal number and size)] in anorexia of cancer show abnormal presynaptic dopaminergic neurotransmission. To determine postsynaptic receptor status, studies were done in tumor-bearing (TB) and non-tumor-bearing (NTB) free-feeding control rats while continuously measuring their food intake via a rat eater meter. When TB rats developed anorexia, TB and control rats were killed, and postsynaptic D1- and D2-receptor mRNA expression in LHA and VMN were measured via RT-PCR. At anorexia, food intake decreased initially by a decrease in meal number, whereas a concurrent increase in meal size occurred for 24 h in an attempt to maintain food intake constant. Then meal size also decreased. At this time, D1- and D2-receptor mRNA expressions in LHA and VMN of TB vs. controls were significantly upregulated. Verification of D1- or D2-receptor changes to changes in meal number and size at anorexia was made by injection of intra-VMN or -LHA dopaminergic receptor antagonists. Intra-VMN D1-receptor antagonist (SCH-23390) in TB rats decreased food intake mainly via a decrease in meal size. Intra-VMN D2-receptor antagonist (sulpiride) in TB rats increased food intake via an increase in meal number and in NTB free-feeding rats by an increase in meal size. Intra-LHA D1-receptor antagonist in TB rats had no effect on food intake or feeding pattern. Intra-LHA D2-receptor antagonist in TB and in NTB free-feeding rats increased food intake via an increase in meal number. Our data provide evidence that postsynaptic dopaminergic receptor subtypes in the hypothalamus are involved in the regulation of meal size, meal number, and thus food intake in anorectic TB rats.
Ingestive responses to administration of stress hormones in baboons
Authors: Shade R. E. , Blair-West J. R. , Carey K. D. , Madden L. J. , Weisinger R. S. , Rivier J. E. , Vale W. W. , Denton D. A.
Published: December 2017

Experimental stress and the administration of the stress hormone ACTH have been reported to stimulate sodium appetite in many nonprimate species. Experiments were conducted to determine whether prolonged intracerebroventricular infusions of the neuropeptides corticotropin-releasing factor (CRF) and urocortin (Ucn), or systemic administration of ACTH, affected ingestive behaviors in a nonhuman primate, the baboon. Intracerebroventricular infusions of CRF or Ucn significantly decreased daily food intake. The decrease with Ucn continued into the postinfusion period. These infusions did not alter daily water intake. Daily voluntary intake of 300 mM NaCl solution was not increased, and there was evidence of reductions on days 2- 4 of the infusions. Intramuscular injections of porcine ACTH or synthetic ACTH (Synacthen) for 5 days did not affect daily NaCl intake, although the doses were sufficient to increase cortisol secretion and arterial blood pressure. Sodium depletion by 3 days of furosemide injections did induce a characteristic sodium appetite in the same baboons. These results demonstrate the anorexigenic action of CRF and Ucn in this primate. Also, CRF, Ucn, and ACTH did not stimulate sodium appetite at the doses used.
Differential effects of an NMDA and a non-NMDA receptor antagonist on medullary lateral tegmental field neurons
Authors: Barman Susan M. , Orer Hakan S. , Gebber Gerard L.
Published: December 2017

We microiontophoresed an N-methyl-d-aspartate (NMDA) and a non-NMDA receptor antagonist onto medullary lateral tegmental field (LTF) neurons, the naturally occurring discharges of which were correlated to the cardiac-related rhythm in sympathetic nerve discharge (SND) of dialurethane-anesthetized cats. Some of these neurons were classified as sympathoexcitatory, because their firing rate decreased during baroreceptor reflex activation. Microiontophoresis of 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo-[ f]quinoxaline-7-sulfonamide (NBQX), a non-NMDA receptor antagonist, reduced the mean firing rates of these neurons (51 ± 8% of control, P < 0.001, n = 20) without affecting their relationship to cardiac-related SND, as indicated by the lack of significant changes in the ratio of peak to background counts in arterial pulse (AP)-triggered histograms of LTF neuronal activity and the AP-LTF coherence value at the frequency of the heartbeat. In contrast, microiontophoresis of D(−)-2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist, onto LTF neurons reduced the ratio of peak to background counts in AP-triggered histograms to 57 ± 9% of control ( P = 0.002, n = 16) and the AP-LTF coherence value to 25 ± 10% of control ( P = 0.001, n = 10). These data support the view that non-NMDA and NMDA receptors are involved in setting the basal level of activity of LTF sympathoexcitatory neurons and in synchronizing their discharges to the AP, respectively.
Ontogeny and insulin regulation of fetal ovine white adipose tissue leptin expression
Authors: Devaskar Sherin U. , Anthony Russ , Hay William
Published: December 2017

Leptin, an adipocyte-derived factor, has multiple biological roles including mitogenesis. We investigated the effect of normal development, acute and chronic hyperglycemia and hypoglycemia, and selective acute hyperglycemia, or hyperinsulinemia, on fetal ovine white adipose tissue (WAT) leptin mRNA concentrations. Leptin mRNA amounts expressed as a ratio to the internal control ribosomal S2 mRNA decreased threefold with advancing gestational age ( P < 0.05). This gestational decrease was opposite to the 10-fold increase in fetal body weight during the same developmental period. Chronic hyperglycemia with hyperinsulinemia led to no change in WAT leptin mRNA concentrations over a 1- to 10-day duration, but it caused a 40% increase over a 14- to 20-day duration ( P< 0.05) along with an increase in fetal body weight ( P< 0.05). In contrast, hypoglycemia with hypoinsulinemia, while not affecting WAT leptin mRNA from 1 to 34 days, resulted in a 50% decline over a 36- to 76-day duration along with a decline in fetal body weight ( P < 0.05). Acute 24-h studies of selective hyperglycemia with euinsulinemia showed no significant change in WAT leptin mRNA, but in response to selective hyperinsulinemia with euglycemia at 24 h, a twofold increase was observed ( P < 0.05). We conclude that fetal WAT leptin mRNA amounts are regulated by fetal development and circulating insulin concentrations. We speculate that chronic in utero metabolic perturbations that alter circulating insulin concentrations affect fetal leptin production that may mediate insulin's influence on fetal growth.
The size principle: a rule describing the recruitment of motoneurons
Authors: Mendell Lorne M.
Published: December 2017

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

McPhedran AM, Wuerker RB, and Henneman E. Properties of motor units in a homogeneous red muscle (soleus) of the cat. J Neurophysiol 28: 71–84, 1965 ( http://jn.physiology.org/cgi/reprint/28/1/71 ).

Wuerker RB, McPhedran AM, and Henneman E. Properties of motor units in a heterogeneous pale muscle (m. gastrocnemius) of the cat. J Neurophysiol 28: 85–99, 1965 ( http://jn.physiology.org/cgi/reprint/28/1/85 ).

Henneman E, Somjen G, and Carpenter DO. Functional significance of cell size in spinal motoneurons. J Neurophysiol 28: 560–580, 1965 ( http://jn.physiology.org/cgi/reprint/28/3/560 ).

Henneman E and Olson CB. Relations between structure and function in the design of skeletal muscles. J Neurophysiol 28: 581–598, 1965 ( http://jn.physiology.org/cgi/reprint/28/3/581 ).

Henneman E, Somjen G, and Carpenter DO. Excitability and inhibitability of motoneurons of different sizes. J Neurophysiol 28: 599–620, 1965 ( http://jn.physiology.org/cgi/reprint/28/3/599 ).
Dynamics of cardiac output and systolic time intervals in supine and upright exercise
Authors: Miyamoto Y. , Higuchi J. , Abe Y. , Hiura T. , Nakazono Y. , Mikami T.
Published: December 2017

Transient and steady-state responses of stroke volume (SV), heart rate (HR), cardiac output (Q), left ventricular ejection time (LVET), preejection period (PEP), and the ratio of LVET to PEP during bicycle exercises of 50 and 100 W were studied in four healthy male subjects in supine and upright postures. A computer-based system in which impedance cardiography was incorporated served to determine the above parameters on a 10-s interval basis. SV remained almost unchanged in response to exercises in a supine posture, whereas it increased significantly in an upright posture, although the individual differences among subjects were found to be large. The half-response times of variables to a step work load were determined. An approximate accordance was observed among the response times for HR, Q, and LVET/PEP. There was an inverse relationship between LVET and HR, the slope of which was found to be steeper in the supine posture than in the upright posture, reflecting the difference between the SV responses in both postures. LVET fell shortly after the cessation of exercise despite the decreasing HR. Inasmuch as the paradoxical reduction of LVET was also found in the case where SV remained unchanged in response to exercise, no changes in SV can be the cause thereof. Thus, a transient increase in ejection rate, which is due to either the increased myocardial contractility or decreased peripheral vascular resistance, may be responsible for the phenomenon.
Assessment of recovery from hyperbaric-induced subfertility in male mice
Authors: Dore C. J. , Halsey M. J. , Monk S. , Wardley-Smith B.
Published: December 2017

This study was designed to investigate whether subfertility in male mice produced by exposure to high pressures of heliox showed any recovery. Male mice were exposed to 50 ATA heliox (controls exposed to 1 ATA air) during one spermatogenic cycle; subsequently each male was housed with 10 untreated females. After 14 days males were removed and housed with 10 more females. This was repeated four times. Male libido, pregnancy rate, pre- or early implantation loss, and fetal survival were determined for each mating. Results showed that all variables were significantly reduced in the pressure group during the first mating, but there were differing rates of recovery. Male libido was consistently reduced (12%) and showed no recovery trend. Pregnancy rate showed continuing improvement throughout all matings but did not reach control levels after 8 wk. Pre/early implantation loss and fetal survival had returned to control values by the fourth mating. These data suggest that pressure-induced subfertility is largely reversible, and at least two separate events contribute to it.
Measurement of lung emptying patterns during slow exhalations
Authors: Scott W. R. , Van Liew H. D.
Published: December 2017

Five subjects slowly inhaled a 200-ml bolus of sulfur hexafluoride (SF6) from residual volume (RV) followed by an O2-Ar mixture to total lung capacity, then exhaled to RV, either slowly or as rapidly as possible. Larger amounts of SF6 and N2 were recovered in fast than in slow exhalations. We calculated the gas volumes of the apical and basal halves of the parenchymal mass as functions of exhaled volume during slow exhalations from 1) the difference between SF6 recovered in slow and fast exhalations and 2) an estimate of the apex-to-base concentration profile of SF6 in the lung after inspiration. The maximal volume difference, where the apex contained 600 ml more gas than the base, occurred when 70% of the vital capacity had been exhaled. The same calculation, but using N2 data, gave unrealistically large volume differences. Apparently SF6 delivered as a bolus results in an apex-to-base gradient that is large relative to intraregional gradients, but dilution of the resident N2 by a non-N2 gas results in sizable intraregional gradients.
Influence of heat stress on exercise-induced changes in regional blood flow in sheep
Authors: Bell A. W. , Hales J. R. , King R. B. , Fawcett A. A.
Published: December 2017

Radioactive microspheres were used to measure cardiac output and blood flow to most major tissues in sheep at rest and during treadmill exercise (3- to 6-fold increase in metabolic rate for 30 min) in thermoneutral (TN) [dry bulb temperature (Tdb) = 16 degrees C, wet bulb temperature (Twb) = 12 degrees C] and mildly hot (MH) (Tdb = 40 degrees C, Twb = 23 degrees C) environments. During exercise, rectal temperature increased more under MH than under TN conditions; exercise-induced changes in the major central cardiovascular parameters were unaffected by MH. Exercise in TN caused mild hypocapnia, and in MH, severe respiratory alkalosis. Skin blood flow in the torso decreased during exercise in TN and MH. Extremity skin blood flow was increased by heat but not exercise. Exercise-induced increases in flows to respiratory muscles and upper respiratory tract tissues were greatly enhanced in MH. Exercise caused large increases in blood flow to fore- and hindlimb muscles, which were less in MH than in TN. Effects of MH on exercise-induced changes in flow to these and other tissues (e.g., abdominal viscera and adipose tissue) are discussed in terms of the conflicting requirements of energy expenditure and body temperature regulation during exercise in sheep and other species, particularly humans.
Cigarette smoke acutely increases collateral resistance in excised dog lobes
Authors: Nakamura M. , Hildebrandt J.
Published: December 2017

The acute effects of cigarette smoke or drug inhalation on collateral conductance (Gcoll) were studied in freshly excised dog lobes held at fixed volumes. A double-lumen catheter was wedged into a segmental bronchus, and air, smoke, or aerosol flowed into the blocked segment at a constant pressure of 2 cmH2O. A capsule glued over a small area of perforated pleura of the segment was used to measure alveolar pressure; the capsule could also be used to measure small airway flow (Vcap) through the segment. Gcoll was almost linearly dependent on lung volume, rising about fivefold between 20 and 100% inflation (30 cmH2O). During smoke inhalation Gcoll began decreasing almost immediately, roughly halving with the first cigarette and falling to about 20% after two cigarettes. Similar proportions were obtained at other lung volumes. Pulmonary conductance (oscillator) in the remainder of the lobe decreased only modestly to 78% of control after two cigarettes. In lobes exposed to 4.5% CO2 after air Gcoll rose 25–50%, but Vcap increased only 5–10%. However, acetylcholine chloride aerosol reduced both flows by similar ratios. Isoproterenol did not prevent or reverse smoke-induced collateral constriction but did reverse the effects of acetylcholine on both pathways. These results suggest that in excised lungs aerosols acted on larger segmental airways in series with collateral channels and with peripheral airways, whereas CO2 and particularly cigarette smoke provoked more marked effects on the most distal smooth muscle.
Relationship of skin surface area to body mass in the immature rat: a reexamination
Authors: Spiers D. E. , Candas V.
Published: December 2017

Skin surface area (Ab) was measured in the rat beginning at birth mass and extending over a range of body mass (m) from 5.0 to 49.3 g. Area of each animal was determined using an elastic impression material. The best-fit relationship between Ab and m over the entire range of mass was Ab = 6.88m0.736. Results suggest, however, that the standard mass exponent of two-thirds, for estimating Ab of adult animals, could also be used for immature animals weighing 14 g or more. In rats weighing less than 14 g, the mass coefficient of the Meeh-Rubner equation varies with m, indicating that the two-thirds exponent is inappropriate for use with very young animals.
Effect of posture on thoracoabdominal movements during CO2 rebreathing
Authors: Chapman K. R. , Rebuck A. S.
Published: December 2017

To determine whether the rib cage and abdomen-diaphragm contributions to tidal volume (VT) during CO2 rebreathing are affected by postural change, using respiratory inductive plethysmography, we measured in eight healthy volunteers the compartmental VT responses to progressive hypercapnia in both seated and supine postures. The ventilatory, frequency, and VT responses to CO2 of the total respiratory system were not significantly different between postures. VT responses, corrected for body size, ranged from 1.67 to 3.71% vital capacity (VC) X Torr-1 (mean 2.27) in seated subjects and from 1.08 to 3.79% VC X Torr-1 (mean 2.06), in supine subjects. In both postures, the VT response of the abdominal compartment was nearly uniform among subjects and independent of the total respiratory system VT response (slope = 0.091, r = 0.210 P greater than 0.3 seated; slope = 0.043, r = 0.077, P greater than 0.3 supine), whereas the VT response of the rib cage varied among subjects and was significantly correlated to the total VT response (slope = 0.815, r = 0.84, P less than 0.01, seated; slope = 1.125, r = 0.859, P less than 0.01, supine). Thus high tidal volume responses to CO2 rebreathing are determined largely by recruitment of the rib cage compartment in both seated and supine postures.