bluuebunny/crossref_metadata_2025 huggingface dataset:
Three types of postsynaptic glutamatergic receptors are activated in DMNX neurons upon stimulation of NTS
Authors: Willis A. , Mihalevich M. , Neff R. A. , Mendelowitz D.
Published: December 2017

While it is widely accepted that parasympathetic activity plays a significant role in cardiovascular, bronchomotor, and gastrointestinal function, little is known about the synaptic control of parasympathetic vagal neurons. In this study, we identified the neurotransmitter(s) and postsynaptic responses in dorsal motor nucleus of the vagus (DMNX) neurons upon stimulation of the nucleus of the solitary tract (NTS). Neurons were visualized in rat brain stem slices, and perforated patch-clamp techniques were used to record postsynaptic currents. NTS stimulation activated glutamatergic currents in DMNX that were separated into N-methyl-D-aspartate (NMDA) and non-NMDA components using D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively. The non-NMDA component was further characterized using cyclothiazide and concanavalin A to block desensitization of DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) and kainate receptors, respectively. Cyclothiazide increased the postsynaptic amplitude, whereas concanavalin A augmented duration, suggesting kainate, but not AMPA, currents are curtailed by desensitization. High frequency stimulations did not alter synaptic efficacy. In conclusion, this study demonstrates the existence of a monosynaptic glutamatergic pathway from NTS that activates NMDA, kainate, and AMPA postsynaptic receptors in DMNX neurons.
Temporal and spatial expression pattern of the angiotensinogen gene in mice and rats
Authors: Niimura F. , Okubo S. , Fogo A. , Ichikawa I.
Published: December 2017

In situ hybridization for mouse angiotensinogen (Ao) mRNA was performed using a Stu I-Pst I 0.43-kb fragment of exon 2 as a template to synthesize RNA probes. The mouse Ao mRNA expression patterns were different from those reported for rats. Ao mRNA was expressed in the fetal liver as early as 12.5 days postcoitus, and the liver remained the predominant organ of its expression in utero. Within the developing kidney, Ao mRNA was demonstrated at 17.5 days postcoitus in the proximal straight tubules undergoing loop formation in the medulla. In the matured mouse kidney, the expression site is within the outer stripe of outer medulla, hence identified as the pars recta, not proximal convoluted tubules. Additional studies revealed that, in rats also, Ao mRNA was localized in the pars recta. This was in contrast to previously published results that showed that Ao mRNA was localized primarily in the proximal convoluted tubules in rats. Thus the pars recta appears to be an important intrarenal source of Ao for both rats and mice throughout pre- and postnatal periods, whereas the liver can be the major extrarenal source in utero in mice, but not in rats.
Central vs. peripheral metabolic control of estrous cycles in Syrian hamsters. II. Glucoprivation
Authors: Schneider J. E. , Goldman M. D. , Leo N. A. , Rosen M. E.
Published: December 2017

Estrous cycles in Syrian hamsters are inhibited by food deprivation or treatment with pharmacological inhibitors of intracellular glucose utilization (glucoprivic treatments). These same metabolic challenges increase neural stimulation in areas of the caudal brain stem thought to be involved in detection of metabolic signals. Experiment 1 was designed to examine whether vagally transmitted signals are important for glucoprivic effects on estrous cycles and on neural stimulation in the caudal brain stem. Vagotomized or sham-operated hamsters were treated with 2-deoxy-D-glucose (2-DG) at a dose known to decrease cellular glucose utilization and inhibit estrous cycles (1,750 mg/kg). Vagotomized and sham-operated hamsters did not differ significantly in incidence of 2-DG-induced anestrus or in neural stimulation in the caudal brain stem, but the effects of 2-DG on estrous cycles and neural stimulation appeared to have been attenuated in vagotomized hamsters. In experiment 2, hamsters were injected intracerebroventricularly with 2-DG or glucose at doses that did not induce anestrus when injected systemically (125 and 250 mg/kg). Groups treated with intracerebroventricular injections of 2-DG showed a significantly higher incidence of anestrus than those treated with glucose. In experiment 3, effects of systemic injections of 2-DG were prevented by prior injection of glucose or fructose at the same concentration, indicating that 2-DG acts via effects on glucose metabolism, rather than via a nonspecific pharmacological effect or generalized stress response. Results of these experiments and those reported elsewhere (J. E. Schneider, A. J. Hall, and G. N. Wade. Am. J. Physiol. 272 (Regulatory Integrative Comp. Physiol, 41) R400-R405, 1997] are consistent with the notion that central glucoprivation is sufficient, whereas peripheral lipoprivation is not critical, for metabolic effects on estrous cycles.
Dissociation of motor activity circadian rhythm in rats after exposure to LD cycles of 4-h period
Authors: Vilaplana J. , Cambras T. , Diez-Noguera A.
Published: December 2017

For > 30 days Wistar rats were subjected to six dark pulses per day (T4 cycles; 3 h light, 1 h dark) to study the possibility of dissociating their motor activity rhythm into distinct circadian components. Rats of both sexes were used, one-half of which were pinealectomized to examine the effect of the pineal gland on the entrainment process. Results show that when rats were maintained under T4 a 4-h rhythm in their motor activity was present. Rats showed anticipatory activity to dark phases, suggesting that the motor activity components are actually entrained to the external light/dark (LD) cycles. When rats were left under constant darkness after T4, some motor activity components coming from the dark phases free ran for several days with different circadian periods. This suggests that the motor activity pattern is generated by several circadian oscillators. Moreover, the free-running components of motor activity after T4 were more evident when T4 was applied after exposure to constant light than after exposure to constant darkness. These results support the hypothesis that the circadian system of the rat is formed by several circadian oscillators, whose degree of coupling depends on light conditions. In constant light, bright light may inhibit internal coupling within the system, making it subsequently more susceptible to the T4 cycles. No differences were observed between pinealectomized and sham-operated animals, although females were more sensitive to T4 cycles than males.
Nitric oxide and pregnancy
Authors: Sladek S. M. , Magness R. R. , Conrad K. P.
Published: December 2017

This review will consider whether nitric oxide (NO) contributes to maternal systemic vasodilation during pregnancy, regulates uterine and fetoplacental blood flow, and is involved in uterine quiescence prior to parturition. Also, whether a deficiency of NO contributes to the hypertensive disorder of pregnancy, preeclampsia, will be considered. The biosynthesis of NO increases in gravid rats and sheep, but the status in normal human pregnancy and preeclampsia is controversial. NO contributes to maternal systemic vasodilation and reduced vascular reactivity during normal pregnancy; however, the relative contribution of NO is variable depending on the animal species, vascular bed, and vessel size. Impaired relaxation responses to acetylcholine, but not bradykinin or NO donors, are observed in small arteries from women with preeclampsia, suggesting a receptor or signal transduction defect, although NO may play little, if any, role here. Uterine arteries have increased endothelial nitric oxide synthase (NOS) activity, protein expression, and guanosine 3',5'-cyclic monophosphate production during pregnancy; however, whether these mediate uterine vasodilation during pregnancy remains to be established. NOS is expressed in the human placental syncytiotrophoblast and in the fetoplacental and umbilical vascular endothelium where basal production of NO contributes to low fetoplacental vascular resistance. Controversy exists over the status of placental NOS in preeclampsia, although an abnormality of umbilical NOS activity is likely. Finally, the uterus has NOS activity, which decreases at the end of gestation, and exogenous NO relaxes the myometrium, but whether endogenous NO contributes to uterine quiescence during pregnancy has yet to be confirmed.
Regulation of fluid intake in dehydrated humans: role of oropharyngeal stimulation
Authors: Figaro M. K. , Mack G. W.
Published: December 2017

We examined the effect of oropharyngeal stimulation on thirst, secretion of arginine vasopressin ([AVP]p), and fluid intake in six healthy adults after dehydration (28.6 +/- 1.4 ml/kg water loss) induced by mild exercise in the heat (2 h, 38 degrees C, relative humidity < 30%). Subjects performed three identical dehydration protocols followed by 75 min of rehydration at 27 degrees C consisting of 1) ad libitum drinking (Con), 2) infusion of a similar volume of water directly into the stomach via a nasogastric tube (Inf) during the first 25 min followed by combined Inf and ad libitum drinking during the remaining 50 min of rehydration; or 3) ad libitum drinking with simultaneous extraction of ingested fluid via a nasogastric tube (Ext). Plasma osmolality (Posm), [AVP]p, fluid intake, and thirst perceptions were measured throughout. On average, for all three protocols, Posm increased 7.8 +/- 0.6 mosmol/kgH2O and plasma volume decreased 4.7 +/- 1.3%, whereas thirst ratings and [AVP]p increased 7.6 +/- 1.3 cm and 3.1 +/- 0.4 pg/ml, respectively. Reflex inhibition of [AVP]p and thirst occurred within 5 min of rehydration in Con and Ext (P < 0.05) but not during Inf, supporting the hypothesis that oropharyngeal reflexes modulate osmotically stimulated thirst and [AVP]p. However, the reduction in [AVP]p during the first 5 min of Ext (-1.1 +/- 0.3 pg/ml) was less than that seen during Con (-2.1 +/- 0.4 pg/ml), suggesting that oropharyngeal stimulation is not the only factor contributing to the rapid reduction in [AVP]p during the first 5 min of drinking. During Con, subjects ingested 20.0 +/- 2.0 ml/kg of water but only drank 15% more (31.3 +/- 7.1 ml/kg) during Ext, demonstrating a clear role of oropharyngeal metering in limiting total fluid intake in humans in the presence of a persistently high dipsogenic drive.
Metabolic acid-base influences on renal thiazide receptor density
Authors: Fanestil D. D. , Vaughn D. A. , Blakely P.
Published: December 2017

The renal responses to metabolic acidosis/alkalosis involve changes in the proximal tubule, loop of Henle, and collecting ducts. We tested for acid- or base-induced changes in the distal convoluted tubule (DCT) by examining the renal density of the DCT's receptor for thiazide-type diuretics (TZR), as estimated by the binding of [3H]metolazone in Wistar-Kyoto rats. TZR density significantly decreased by 17% in rats ingesting NH4Cl for 3.5 days and by nearly 30% after 7 days; TZR increased up to 40% in rats ingesting NaHCO3 for 2-4 days but was no longer significantly increased after 7 days. Urinary excretion of chloride increased as renal density of the TZR decreased, a finding consistent with the interpretation that acidosis/alkalosis not only altered TZR density but coordinately altered reabsorption of NaCl by the thiazidesensitive Na-Cl cotransporter. The result is that delivery of Na from DCT is enhanced during acidosis and decreased during alkalosis, assisting in compensatory changes in distal nephron secretion of hydrogen ion. The integrated renal response to metabolic acidosis/alkalosis involves a decrease in renal TZR with acidosis and an increase in TZR with alkalosis.
Role of the renal medulla in volume and arterial pressure regulation
Authors: Cowley A. W.
Published: December 2017

The original fascination with the medullary circulation of the kidney was driven by the unique structure of vasa recta capillary circulation, which Berliner and colleagues (Berliner, R. W., N. G. Levinsky, D. G. Davidson, and M. Eden. Am. J. Med. 24: 730-744, 1958) demonstrated could provide the economy of countercurrent exchange to concentrate large volumes of blood filtrate and produce small volumes of concentrated urine. We now believe we have found another equally important function of the renal medullary circulation. The data show that it is indeed the forces defined by Starling 100 years ago that are responsible for the pressure-natriuresis mechanisms through the transmission of changes of renal perfusion pressure to the vasa recta circulation. Despite receiving only 5-10% of the total renal blood flow, increases of blood flow to this region of the kidney cause a washout of the medullary urea gradient and a rise of the renal interstitial fluid pressure. These forces reduce tubular reabsorption of sodium and water, leading to a natriuresis and diuresis. Many of Starling's intrinsic chemicals, which he named "hormones," importantly modulate this pressure-natriuresis response by altering both the sensitivity and range of arterial pressure around which these responses occur. The vasculature of the renal medulla is uniquely sensitive to many of these vasoactive agents. Finally, we have found that the renal medullary circulation can play an important role in determining the level of arterial pressure required to achieve long-term fluid and electrolyte homeostasis by establishing the slope and set point of the pressure-natriuresis relationship. Measurable decreases of blood flow to the renal medulla with imperceptible changes of total renal blood flow can lead to the development of hypertension. Many questions remain, and it is now evident that this is a very complex regulatory system. It appears, however, that the medullary blood flow is a potent determinant of both sodium and water excretion and signals changes in blood volume and arterial pressure to the tubules via the physical forces that Professor Starling so clearly defined 100 years ago.
Myoglobin enhances cardiac performance in antarctic icefish species that express the protein
Authors: Acierno R. , Agnisola C. , Tota B. , Sidell B. D.
Published: December 2017

Channichthyid icefishes of Antarctica are unique among adult vertebrates. All icefish species lack hemoglobin and red blood cells in their circulating blood. All icefishes examined to date also lack the intracellular oxygen-binding protein myoglobin (Mb) in their oxidative skeletal muscles. However, some icefish species do express Mb in their heart ventricles. It is unknown whether Mb in those species in which it is present represents an evolutionary relic or has functional significance. To address this problem, we compared mechanical performance of isolated, perfused hearts from two species of icefish in which Mb is either present (Chionodraco rastrospinosus) or is absent (Chaenocephalus aceratus). Hearts were challenged with increasing afterload (2.5-4.0 kPa) under conditions of defined basal flow (approximately 100 ml.min-1.kg-1), in both the presence and absence of 5 mM sodium nitrite, a Mb poison. Unlike hearts from C. aceratus, which were unable to maintain a constant cardiac output under pressure loading, those from C. rastrospinosus retained a constant flow up to 3.5 kPa afterload. At the upper range of power outputs, hearts of Mb-lacking C. aceratus display greater oxygen utilization than those of Mb-containing C. rastrospinosus. Poisoning of Mb significantly impaired the ability of C. rastrospinosus hearts to face pressure loading without reduction in flow, whereas those of C. aceratus were refractory to the treatment. The results strongly support a functional role for Mb in the former species.
Neuroanatomic organization of the parasympathetic bronchomotor system in developing sheep
Authors: Perez Fontan J. J. , Velloff C. R.
Published: December 2017

We applied two complementary retrograde labeling techniques to characterize the organization of the brain stem neuronal network responsible for the vagal innervation of the trachealis muscle in developing sheep. Single neuronal labeling produced by injections of the beta-subunit of cholera toxin into the muscle in newborn lambs showed that airway vagal preganglionic neurons are located exclusively in the nucleus ambiguous and nucleus of the solitary tract. Transneuronal labeling produced by similar injections of the Bartha strain of the pseudorabies virus in sheep fetuses demonstrated that these airway vagal preganglionic neurons receive inputs from a small number of neurons in brain stem areas known to participate in premotor control of the respiratory muscles (ventral respiratory group), chemoreception (nucleus of the solitary tract and ventral medullary surface), and cardiovascular and respiratory regulation (raphe nuclei, ventrolateral medulla, and noradrenergic groups of the medulla and pons). We conclude that the vagal preganglionic neurons that project to airway smooth muscle are already integrated in the control of breathing before birth in sheep.
Structural and biochemical analyses of cardiac ventricular enlargement in cold-acclimated striped bass
Authors: Rodnick K. J. , Sidell B. D.
Published: December 2017

We examined effects of temperature acclimation on ultrastructural characteristics of cardiac myocytes and maximal activities of metabolic enzymes in cardiac tissue of striped bass (Morone saxatilis). Ventricular mass and ventricular mass divided by body weight were significantly increased (29% and 40%, respectively) in animals acclimated to cold (5 degrees C) vs. warm temperatures (25 degrees C). Mean myocyte diameter was increased at cold temperature (3.47 +/- 0.14 vs. 2.98 +/- 0.08 microns), which is sufficient to explain the increase in ventricular mass. Ventricular enlargement did not alter volume densities of mitochondria, myofibrils, protein concentration, or citrate synthase activity. Thus total volume of mitochondria and myofibrils increased proportionately with cardiac mass in cold animals. Activities of hexokinase (34%) and carnitine palmitoyltransferase (42%) increased in cold animals, suggesting positive compensation and increased aerobic capacity for utilization of glucose and fatty acids for energy production. Enlargement of the ventricle and an increased capacity for ATP production in striped bass may help compensate for kinetic constraints at cold temperatures and maintain circulatory support to oxidative axial musculature for swimming activity.
Endothelin and nitric oxide interact to regulate stretch-induced ANP secretion
Authors: Skvorak J. P. , Dietz J. R.
Published: December 2017

The purpose of this study was to determine the nature of the permissive effect of atrial stretch on atrial natriuretic peptide (ANP) secretion and the mechanism for the rapid termination of endothelin (ET) signaling following the removal of ET-dependent stimuli. Basal ANP release was not affected by either an elevation or inhibition of nitric oxide (NO) activity, but stretch-stimulated ANP release was significantly reduced from 144 +/- 20% to -3 +/- 7% of the baseline by increased NO activity. Furthermore, while the response to ET alone at low pressure was 37 +/- 13% of the baseline ANP secretion rate (P > 0.05), this response increased to 137 +/- 27% (P < 0.05) when NO activity was blocked, a response equal to the control high-pressure response (144 +/- 20%). Thus the reduction in NO activity is a permissive effect of stretch, and NO can rapidly terminate an ET-stimulated ANP response. Therefore, stretch-induced ANP secretion is regulated by a reciprocal interaction between locally produced ET, which appears to increase, and NO, which appears to decrease.
Induction of cardiac natriuretic peptide gene expression in rats trained in hypobaric hypoxic conditions
Authors: Perhonen M. , Takala T. E. , Vuolteenaho O. , Mantymaa P. , Leppaluoto J. , Ruskoaho H.
Published: December 2017

Adaptation of cardiac muscle to prolonged hypobaric hypoxia (770-740 mbar, 2,250-2,550 m), endurance training, and their combination was studied in rats by investigating the gene expression of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in atria and ventricles. Rats were assigned into the following groups according to the barometric conditions and physical activity; normobaric sedentary (NS), normobaric training, hypobaric sedentary (HS), and hypobaric training (HT). Experimental periods were 10, 21, and 56 days; the groups at 91 days served as recovery groups from exposure to and training in normobaric and hypobaric conditions for 56 days. The right ventricular hypertrophy in HT rats at 10 days and 56 days was associated with elevated BNP mRNA levels (2.1- and 1.7-fold, P < 0.05, respectively), whereas hypobaric exposure without training was not sufficient to significantly increase ventricular BNP gene expression, although it lead to hypertrophy of the right ventricle. Right and left atrial BNP mRNA levels were also increased (up to 3.9-fold, P < 0.01) in 10-day HS and 10-day HT groups. ANP mRNA levels in right ventricle and left ventricular epicardium were over twofold higher (P < 0.05-0.01) in 10-day HS and 10-day HT groups in comparison to 10-day NS group. Plasma immunoreactive ANP concentration was increased (P < 0.05) in both hypobaric groups up to 21 days. The results show that exposure to hypobaric hypoxia itself and endurance training in hypobaric, hypoxic conditions lead to a marked early increase in ventricular and atrial ANP and BNP mRNA levels. The adaptational response to hypoxia was more pronounced when the oxygen availability was lowered additionally by endurance training carried out in hypobaric hypoxic conditions.
The vagus nerve in the thermoregulatory response to systemic inflammation
Authors: Romanovsky A. A. , Simons C. T. , Szekely M. , Kulchitsky V. A.
Published: December 2017

Experimentally, systemic inflammation induced by a bolus intravenous injection of lipopolysaccharide (LPS) may be accompanied by three different thermoregulatory responses: monophasic fever (the typical response to low doses of LPS), biphasic fever (medium doses), and hypothermia (high doses). In our recent study [Romanovsky, A. A., V. A. Kulchitsky, C. T. Simons, N. Sugimoto, and M. Szekely. Am. J. Physiol. (Regulatory Integrative Comp. Physiol.). In press], monophasic fever did not occur in subdiaphragmatically vagotomized rats. In the present work, we asked whether vagotomy affects the two other types of thermoregulatory response. Adult Wistar rats were vagotomized (or sham operated) and had an intravenous catheter implanted. On day 28 postvagotomy, the thermal responses to the intravenous injection of Escherichia coli LPS (0, 1, 10, 100, or 1,000 micrograms/kg) were tested in either a neutral (30 degrees C) or slightly cool (25 degrees C) environment. Three major results were obtained. 1) In the sham-operated rats, the 1 microgram/kg dose of LPS caused at 30 degrees C a monophasic fever with a maximal colonic temperature (Tc) rise of approximately 0.6 degree C; this response was abated (no Tc changes) in the vagotomized rats. 2) At 30 degrees C, all responses to higher doses of LPS (10-1,000 micrograms/kg) were represented by biphasic fevers (the higher the dose, the less pronounced the first and the more pronounced the second phase was); none of these biphasic fevers was altered in the vagotomized animals. 3) In response to the 1,000 micrograms/kg dose at 25 degrees C, hypothermia occurred: Tc changed by -0.5 +/- 0.1 degree C (nadir); this hypothermia was exaggerated (-1.1 +/- 0.1 degrees C) in the vagotomized rats. It is concluded that vagal afferentation may be important in the mediation of the response to minor amounts of circulating LPS, whereas the response to larger amounts is brought about mostly (if not exclusively) by nonvagal mechanisms. This difference may be explained by the dose-dependent mechanisms of the processing of exogenous pyrogens. Vagotomized animals also appear to be more sensitive to the hypothermizing action of LPS in a cool environment; the mechanisms of this phenomenon remain speculative.
Intracellular pH response to hypercapnia in neurons from chemosensitive areas of the medulla
Authors: Ritucci N. A. , Dean J. B. , Putnam R. W.
Published: December 2017

We investigated whether neurons in two chemosensitive areas of the medulla oblongata [nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM)] respond to hypercapnia differently than neurons in two nonchemosensitive areas of the medulla oblongata [inferior olive (IO) and hypoglossal nucleus (Hyp)]. Medullary brain slices from preweanling Sprague-Dawley rats were loaded with 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein, and intracellular pH (pHi) was followed in individual neurons at 37 degrees C with the use of a fluorescence imaging system. Most neurons from the NTS and VLM did not exhibit pHi recovery when CO2 was increased from 5 to 10% at constant extracellular HCO3- concentration [extracellular pH (pHo) decreased approximately 0.3 pH unit] (hypercapnic acidosis). However, when CO2 was increased from 5 to 10% at constant pHo (isohydric hypercapnia), pHi recovery was seen. In contrast, all neurons from the IO and Hyp exhibited pHi recovery during hypercapnic acidosis. All pHi recovery in the four areas studied was inhibited by 1 mM amiloride and unaffected by 0.5 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. These data indicate that 1) pHi regulation differs between neurons in chemosensitive (NTS and VLM) and nonchemosensitive (IO and Hyp) areas of the medulla, 2) pHi recovery is due solely to Na+/H+ exchange in all four areas, and 3) Na+/H+ exchange is more sensitive to inhibition by extracellular acidosis in NTS and VLM neurons than in IO and Hyp neurons.
Angiotensins stimulate catecholamine release from the chromaffin tissue of the rainbow trout
Authors: Bernier N. J. , Perry S. F.
Published: December 2017

Immunohistochemical and pharmacological techniques were utilized to investigate the relationships between angiotensins and catecholamine release from the chromaffin tissue of rainbow trout (Oncorhynchus mykiss). Double labeling with [Asp1, Ile5]angiotensin II-fluorescein isothiocyanate (ANG II-FITC) and anti-dopamine beta-hydroxylase revealed specific ANG II binding sites on chromaffin cells. Injection (1 nmol/kg body wt) of either ANG II-FITC, [Asn1, Val5, Asn9]ANG I, [Asp1, Ile5, His9]ANG I, [Asn1, Val5]ANG II, [Asp1, Val5]ANG II, or [Asp1, Ile5]ANG II elicited catecholamine release from in situ perfusion preparations of the head kidney. Catecholamine release elicited by [Asn1, Val5]ANG II (10(-13) to 10(-7) mol/kg body wt) was dose dependent, and the secretion of epinephrine (Epi) was greater than that of norepinephrine (NE). Relative to the results obtained with the [Asn1, Val5]ANG II treatment (1 nmol/kg body wt), Epi release was 72 and 82% lower in response to injections (1 nmol/kg body wt) of [Asn1, Val5]ANG I [amino acid (AA) positions 1-7] and [Asn1, Val5]ANG I (AA 1-6), respectively. Pretreatment with either losartan (10(-5) M), PD-123319 (10(-5) M), or hexamethonium (10(-3) M) had no effect on [Asn1, Val5]ANG II-elicited catecholamine release. Pretreatment with captopril (10(-4) M) significantly reduced [Asn1, Val5, Asn9]ANG I-elicited Epi and NE release and decreased basal catecholamine release. These results provide direct evidence that angiotensins can elicit catecholamine release from the chromaffin tissue via specific ANG II binding sites and indicate that the synthesis of ANG II may be either local or systemic.
Hyperplasia and hypertrophy of chicken cardiac myocytes during posthatching development
Authors: Li F. , McNelis M. R. , Lustig K. , Gerdes A. M.
Published: December 2017

For characterization of the growth pattern of cardiac myocytes during posthatching development, cardiac myocytes were enzymatically isolated from the ventricles of 1-, 15-, 29-, and 42-day-old chickens for measurement of myocyte nucleation, length, width, volume, and number, and for immunolabeling of cytoskeletal proteins. Ventricular myocyte number increased 156% from day 1 to day 42. Average cell volume increased more than 400%, and myocytes lengthened 125%, but cell width only increased 53% during this period. All myocytes were mononucleated at day 1. At day 15, 18% of myocytes became binucleated with < 1% of myocytes containing more than two nuclei. Interestingly, binucleated myocytes were able to divide with two nuclei going through mitosis at the same time. As demonstrated by staining with tubulin and alpha-actinin antibodies, two mitotic spindles and two cleavage furrows were formed in dividing binucleated myocytes. At day 42, binucleated myocytes increased to 44% with 11% of myocytes containing more than two nuclei. Sarcomeric alpha-actinin was partially disassembled in prometaphase and was reorganized into regular Z lines of sarcomeres in telophase. Desmin was disassembled in prophase and was reassembled during late telophase. These results suggest that chicken myocytes undergo hypertrophy and continue to proliferate during posthatching maturation, although it is currently believed that myocytes of all vertebrates withdraw from the cell cycle shortly after birth. We provide direct evidence for the first time of in vivo myocyte division in 6-wk-old chicken hearts.
Linear and nonlinear properties of heart rate control in infants at risk
Authors: Patzak A. , Schluter B. , Orlow W. , Mrowka R. , Gerhardt D. , Schubert E. , Persson P. B. , Barschdorff D. , Trowitzsch E.
Published: December 2017

The aim of this study was to test whether the heart rate (HR) control in infants at risk differs in comparison with healthy infants. Twelve former preterm infants suffering from bronchopulmonary dysplasia and 18 control infants, matched for their postconceptional age, were examined polygraphically during quiet and active sleep. HR, low-frequency (LF) power, high-frequency (HF) power, total power, and the ratio of LF to HF power (LF/HF) of the instantaneous HR spectra were calculated for linear analysis. The largest Lyapunov exponent (LLE) of the R-R interval time series was calculated to determine a nonlinear property of HR. Infants at risk had significantly lower LF power (median: 0.51 x 10(-3) vs. 1.16 x 10(-3) Hz2) and lower LF/HF (median: 1.05 vs. 1.94) during quiet sleep. LLE was positive, revealing low-dimensional chaotic behavior of HR control, and did not differ between both groups (median: quiet sleep, 0.05 bit/s vs. 0.06 bit/s; active sleep, 0.16 bit/s vs. 0.15 bit/s). Sleep state-related changes in spectral parameters and LLE were similar in both groups. In infants at risk, the lower LF/HF during quiet sleep can be interpreted in terms of changes in the rhythmic components of the sympathovagal balance of the autonomic system, which is an expression of linear properties of HR control. Conversely, the lack of differences in LLE between both groups indicates similar nonlinear properties of the control system.
Mechanisms compensating Na and water retention induced by long-term reduction of renal perfusion pressure
Authors: Seeliger E. , Boemke W. , Corea M. , Encke T. , Reinhardt H. W.
Published: December 2017

Endogenous downregulation of plasma aldosterone (Aldo) concentration, despite increased plasma renin activity (PRA), has been suggested to compensate Na and water retention, which is induced by long-term reduction of renal perfusion pressure (rRPP). To determine whether fixed plasma Aldo concentration would prevent equilibration of 24-h Na and water balances during rRPP, chronically instrumented, freely moving beagle dogs were kept under standardized conditions (daily intake 5.5 mmol Na/kg body wt) and studied for 4 consecutive days under the following conditions: control without rRPP (protocol 1) and rRPP + infusion of Aldo (rRPP + Aldo, protocol 2). Because Aldo administration reduces PRA and, thereby, angiotensin II (ANG II) levels ANG II was additionally infused in protocol 3 (rRPP + ANG II + Aldo). During rRPP + Aldo, 24-h Na balances were never equilibrated. Daily Na retention was approximately 3.5 mmol/kg body wt on day 1 and decreased to approximately 1.6 mmol/kg body wt on day 4; 24-h water balances changed in a similar manner. PRA decreased stepwise. On all rRPP + ANG II + Aldo days, Na and water retentions were more extensive than during rRPP + Aldo. Daily Na retention decreased from approximately 4.4 mmol/kg body wt on day 1 to approximately 3.0 mmol/kg body wt on day 4. Plasma atrial natriuretic peptide increased during both protocols. It is concluded that 1) endogenous downregulation of components of the renin-angiotensin-aldosterone system is a pivotal compensatory mechanism to reduce Na and water retention and 2) natriuretic and diuretic factors seem to be of minor potency, because not even the sum of all could counterbalances the Na- and water-retaining effects of Aldo and ANG II.
Natural osmolyte trimethylamine N-oxide stimulates tubulin polymerization and reverses urea inhibition
Authors: Sackett D. L.
Published: December 2017

The natural osmolyte trimethylamine N-oxide (TMAO) is one of the methylamine compounds often accumulated by diverse organisms in response to osmotic stress and/or to compensate for the deleterious effects of urea. Tubulin polymerization is promoted by TMAO. At 1 M TMAO, tubulin polymers are produced with properties expected of normal steady-state microtubules (MT): polymerization is reversed by exposure to cold or the antimitotic drug podophyllotoxin, a critical concentration for polymerization at 30 degrees C of 1.5 microM is found, and the morphology of the polymers in electron micrographs is typical of MT and ribbons, or open MT. At 2 M TMAO, polymerization is very rapid and hyperstable polymers are formed. These are resistant to cold-induced depolymerization although still sensitive to podophyllotoxin inhibition. A lower critical concentration of 0.7 microM is observed, and electron micrographs reveal MT, ribbons, and other polymer forms not usually stable, such as splayed protofilaments. Inhibition of tubulin polymerization by low concentrations of urea (Sackett, D. L., B. Bhattacharyya, and J. wolff. Biochemistry 33: 12868-12878, 1994) is largely reversed by the presence of TMAO at one-half the molarity of urea, the physiological ratio observed in cartilaginous fishes. Other methylamines, including betaine, dimethylglycine, glycine, and sarcosine, failed to stimulate MT polymerization or protect against urea inhibition. Trimethylamine, taurine and glycylglycine inhibit polymerization. TMAO did not interfere with binding of MT-associated proteins (MAP) and protected both tubulin assembly and MAP binding from urea.
Two types of leptin-responsive gastric vagal afferent terminals: an in vitro single-unit study in rats
Authors: Wang Y. H. , Tache Y. , Sheibel A. B. , Go V. L. , Wei J. Y.
Published: December 2017

In vitro gastric vagal afferents' (GVAs) unit activities were recorded from the ventral GVA nerve strands in rats. The responsiveness of 16 GVA terminals to close intra-arterial injection of vehicle (0.1 ml), leptin (350 pmol), and cholecystokinin (CCK)-8 (10 pmol) was analyzed to generate a spike count-versus-time histogram. Data of 5-min spike counts before and after each treatment were normalized by dividing the latter by the former. A quotient (Q) > 1 indicates an excitatory effect, Q < 1 indicates an inhibitory effect, and Q close to 1 indicates no effect. Two types of GVA terminals were identified. Type 1 (n = 8) responded to leptin with Q > 1; CCK-8 pretreatment did not consistently alter leptin sensitivity. In contrast, Type 2 (n = 8) responded to leptin with Q < 1 or close to 1, and CCK-8 pretreatment increased the leptin sensitivity so that the terminals responded to subsequent leptin with Q > 1. These data suggest that Type 1 and Type 2 GVA terminals may provide afferent neural signals, which, in turn, will be involved in body weight and food intake control systems, respectively.
Endocrine effects of pregnancy and exposure to a simulated open field in rats
Authors: Smith F. G. , Fewell J. E. , Abu-Amarah I.
Published: December 2017

In adult rats, exposure to a novel environment, such as a simulated open field, elicits an increase in body core temperature. We have recently shown that this response is attenuated in midpregnancy and abolished at term of pregnancy in rats. We postulated that this gestation-dependent response resulted from alterations in the hypothalamic-pituitary-adrenal axis. To test this hypothesis, we measured the effects of pregnancy on renin, corticosterone, and arginine vasopressin (AVP) responses to exposure to either a simulated open field (30 or 120 min) or to the home cage (30 or 120 min) in rats. Pregnancy increased renin and corticosterone levels but not plasma AVP levels. Exposure to an open field decreased renin and increased plasma AVP levels in nonpregnant rats and on days 15 and 20 of gestation in pregnant rats, compared with home cage responses. Serum corticosterone levels were elevated after exposure to an open field in nonpregnant and pregnant rats, compared with home cage rats, the effect being more prolonged on day 20 of gestation. These observations provide new information on endocrine changes during pregnancy in rats and may help to explain the attenuated stress-induced hyperthermic response to exposure to a novel environment seen near term of pregnancy.
Increase in muscle IGF-I protein but not IGF-I mRNA after 5 days of endurance training in young rats
Authors: Eliakim Alon , Moromisato Mark , Moromisato David , Brasel Jo Anne , Roberts Charles , Cooper Dan M.
Published: December 2017

Five days of treadmill training in rats leads to increased muscle size and running time. This was used to examine the effect of exercise on circulating insulin-like growth factor I [IGF-I; radioimmunoassay (RIA)], local muscle (hindlimb) IGF-I (by RIA), and muscle IGF-I mRNA (by ribonuclease protection assay). Eight-week-old female Sprague-Dawley rats were divided into three groups: control ( n = 10); single-exercise test ( n = 10), untrained but with one maximal exercise test at the end of the study; and training ( n = 16), trained for 5 days and one maximal exercise test on day 6. There were no differences among the groups with respect to circulating IGF-I. Muscle IGF-I protein in trained rats (4.2 ± 1.5 ng/g of muscle tissue) was significantly greater than both control (0.27 ± 0.1 ng/g) and single-exercise test (0.62 ± 0.19 ng/g, P < 0.05 by analysis of variance). There was no difference among the groups in IGF-I mRNA gene expression. These data suggest that there is an early, marked, local muscle increase in IGF-I protein in response to exercise. This increase, however, may not be related to increased muscle IGF-I gene expression. Moreover, the IGF-I response was probably local in nature since it was not matched by any increase in circulating IGF-I.
The imidazoline receptor in control of blood pressure by clonidine and allied drugs
Authors: Reis Donald J. , Piletz John E.
Published: December 2017

Clonidine, moxonidine, and rilmenidine are centrally acting antihypertensive agents that lower arterial pressure by inhibiting the tonic activity of sympathoexcitatory neurons in the rostral ventrolateral medulla. Competing hypotheses have been put forward by different investigators to explain the sympathoinhibition evoked by “imidazoline drugs”: either via central actions at α2-adrenergic receptors or novel I1-imidazoline receptors. These different perspectives are presented in the accompanying reviews.
Physiology of transgenic mice with brown fat ablation: obesity is due to lowered body temperature
Authors: Klaus Susanne , Münzberg Heike , Trüloff Christiane , Heldmaier Gerhard
Published: December 2017

We investigated the physiological basis for development of obesity in uncoupling protein-diphtheria toxin A chain (UCP-DTA) transgenic mice. In these mice the promoter of the brown adipose tissue (BAT)-specific UCP was used to drive expression of DTA, resulting in decreased BAT function and development of obesity and insulin resistance (Lowell, B. B., S. V. Susulic, A. Hamann, J. A. Lawitts, J. Himms-Hagen, B. B. Boyer, L. Kozak, and J. S. Flier. Nature 366: 740–742, 1994). In adult UCP-DTA mice, we measured food intake and food assimilation, locomotor activity, metabolic rate, and body temperature in comparison to control animals. No differences could be observed in food intake or assimilation and locomotor activity. Weight-specific metabolic rates at temperatures between 20 and 37°C, however, were consistently lower in transgenic mice. Continuous telemetric recording of core body temperature showed that transgenic mice displayed a downshift in body temperature levels of ∼0.9°C. In summary, we provide evidence that attenuated body temperature levels alone can be responsible for development of obesity and that BAT thermogenesis is a major determinant of body temperature levels in rodents.
Repeated intermittent stress exacerbates myocardial ischemia-reperfusion injury
Authors: Scheuer Deborah A. , Mifflin Steven W.
Published: December 2017

Chronic stress in humans has been correlated with increased risk for ischemic heart disease. Thus experiments were conducted to determine if repeated intermittent restraint stress increased infarct size in a rat model of myocardial ischemia-reperfusion injury. Male Sprague-Dawley rats were subjected to no stress (control) or to daily restraint stress for 1–1.5 h for 8–14 days (stress protocol A) or for 2 h daily for 11 or 12 days (stress protocol B). Myocardial ischemia-reperfusion (30-min ischemia, 3-h reperfusion) was performed in anesthetized rats. Average baseline arterial pressures were 111 ± 4, 120 ± 10, and 125 ± 7 mmHg in the control, stress protocol A, and stress protocol B groups, respectively. Infarct size (%area at risk) was significantly larger in both groups of stressed rats compared with control rats (58 ± 5, 78 ± 2, and 79 ± 3% in the control, stress protocol A, and stress protocol B groups, respectively). During ischemia or early reperfusion, zero of eight control, two of six protocol A stress, and two of five protocol B stress rats had at least one period of severe arrhythmia. Therefore, these results provide experimental evidence corroborating correlative studies in humans that link chronic stress with increased morbidity and mortality from ischemic heart disease.
Effect of intravenous glucose and euglycemic insulin infusions on short-term appetite and food intake
Authors: Chapman Ian M. , Goble Elizabeth A. , Wittert Gary A. , Morley John E. , Horowitz Michael
Published: December 2017

To investigate the short-term effects of insulin on feeding, 14 fasting, young adults received 150-min euglycemic intravenous infusions of control (C), low-dose (LD, 0.8 mU ⋅ kg−1 ⋅ min−1), and high-dose (HD, 1.6 mU ⋅ kg−1 ⋅ min−1) insulin and ate freely from a buffet meal during the last 30 min. Steady-state preprandial plasma insulin concentrations were 5.9 ± 0.7 (C), 47 ± 2 (LD), and 95 ± 6 (HD) μU/ml and increased 56–59 μU/ml during the meal. No effect of treatment type on hunger or fullness ratings, duration of eating, or the weight, energy content (1,053 ± 95 kcal, C; 1,045 ± 101 kcal, LD; 1,066 ± 107 kcal, HD; P = 0.9), and composition of food eaten was observed. On a fourth study day, 12 of the subjects received an intravenous infusion of glucose only (Glc) that was identical to the glucose infusion on their HD insulin day. Mean venous glucose concentration was 9.3 ± 0.5 mmol [ P < 0.001 vs. C (5.3 ± 0.1), LD (5.2 ± 0.2), and HD (5.2 ± 0.2)], and plasma insulin increased to 45 ± 2.3 μU/ml at the start and 242 ± 36 μU/ml at the end of the meal. Energy intake during the meal was (∼15%) reduced (1,072 ± 97 kcal, C; 1,086 ± 102 kcal, LD; 1,088 ± 105 kcal, HD; 919 ± 115 kcal, Glc; P < 0.05 Glc vs. C, LD, and HD). Plasma insulin normally increases to ∼100 μU/ml after a mixed meal in lean subjects. Therefore, in the absence of altered blood glucose concentrations, physiological concentrations of insulin are unlikely to play a role in meal termination and the short-term control of appetite.
Atrial natriuretic peptide and mechanisms of cardiovascular control. Role of serotonergic receptors
Authors: Deliva Robin Donna , Ackermann Uwe
Published: December 2017

Atrial natriuretic peptide (ANP) inhibits renal sympathetic nerve activity (RSNA), provided the vagi are intact. Afferents from chemosensitive cardiopulmonary receptors are specifically required. Such receptors produce the Bezold-Jarisch reflex, are prominent on the ventricular epicardium, and are richly supplied with 5-hydroxytryptamine type 3 (5-HT3) receptors. We tested the hypothesis that epicardial 5-HT3-sensitive neurons mediate depressor effects of ANP. Through a special catheter, anesthetized, sinoaortically denervated rats received pericardial test injections of ANP (28-amino acid rat ANP; 100 and 1,000 ng) in the presence or absence of 5-HT3 antagonist (Ondansetron, 20 μg/kg; n = 9). In other groups we observed the effects of systemic ANP while blocking either epicardial or systemic 5-HT3 receptors. Arterial blood pressure (ABP), heart rate, and RSNA were recorded continuously. Intravenous ANP (100 or 200 ng) decreased ABP and RSNA significantly. In contrast, intrapericardial ANP (100 or 1,000 ng) caused no significant fall in ABP or RSNA. Both intravenous and pericardial Ondansetron reduced the effects of intravenous ANP significantly, but the intravenous antagonism was significantly greater. We conclude that epicardial chemosensitive afferents are not sensitive to ANP and that sympathoinhibitory effects of ANP arise from a 5-HT3 agonist that cannot be produced when ANP is confined to the pericardial space.
Seasonal differences in resting oxygen consumption, respiratory quotient, and free thyroxine in woodchucks
Authors: Rawson Richard E. , Concannon Patrick W. , Roberts Paul J. , Tennant Bud C.
Published: December 2017

The relationships among seasonal differences in body weight, food intake, metabolism, and thyroid hormone in woodchucks were investigated in 12 woodchucks. Six woodchucks had been maintained on a photoperiod simulating that found at 42°N (boreal woodchucks). The other group of six animals had been maintained similarly in all respects except that the light simulated that found at 42°S (austral woodchucks). An open-flow respirometer, calibrated using the N2-dilution method, was used to determine metabolism twice in a 2-wk period near the September equinox, while at the same time food intake, body weight, and free thyroxine concentrations (fT4) were measured. Body weight was the same for both groups of woodchucks. However, compared with boreal animals near their autumnal equinox, austral woodchucks near their vernal equinox had significantly higher ( P < 0.01) daily food intake (5 ± 2 vs. 35 ± 2 g ⋅ kg−1 ⋅ day−1), oxygen consumption (4.4 ± 0.3 vs. 7.3 ± 0.3 ml ⋅ min−1 ⋅ kg−1), carbon dioxide production (2.8 ± 0.2 vs. 6.0 ± 0.2 ml ⋅ min−1 ⋅ kg−1), respiratory quotient (0.65 ± 0.01 vs. 0.82 ± 0.02), and fT4 (0.21 ± 0.01 vs. 0.65 ± 0.05 ng/dl). It was concluded that photoperiod has a strong effect on resting metabolism in the woodchuck and that there is an association between fT4 and changes in food intake and metabolic rate.