bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of local tissue cooling on microvascular smooth muscle and postjunctional alpha 2-adrenoceptors
Authors: Faber J. E.
Published: December 2017

The effect of local tissue cooling on microvascular smooth muscle contractile behavior and sensitivity to adrenergic constriction was examined in rat cremaster skeletal muscle. Intravital microscopy was used to measure the diameter of first- and second-order arterioles (control diam = 101 +/- 7 microns) and venules (diam = 142 +/- 9 microns), and third-order terminal arterioles (diam = 19 +/- 4 microns). Norepinephrine (NE) was added to the cremaster bath to produce a 20-35% reduction in control diameter obtained at 34 degrees C bath temperature (in situ cremaster temperature). In the presence of NE, cooling the bath to 26 degrees C caused additional constriction of large arterioles and venules. Terminal arterioles exhibited a more pronounced cooling-induced constriction. Spontaneous vasomotion, evident only in this vessel type, was abolished by cooling. Cooling-induced constriction and inhibition of vasomotion were readily reversible with rewarming to 34 degrees C. Blockade of postjunctional alpha 2-adrenoceptors with yohimbine (1-5 X 10(-7) M) completely abolished cooling-induced constriction, as did the alpha 1- and alpha 2-adrenoceptor antagonist phentolamine (10(-6) M); blockade of alpha 1-adrenoceptors with prazosin (10(-8) M) had no effect on the response. After inhibition of the noradrenergic constriction with yohimbine or phentolamine, local cooling dilated terminal arterioles; however, the dilation was transient. These data suggest that modest tissue cooling has a direct, although transient, depressant effect on microvascular smooth muscle tone. However, in the presence of adrenergic constriction, the inhibitory effect of local tissue cooling is overcome by a selective increase in alpha 2- but not alpha 1-mediated vasoconstriction.
Elevated ambient oxygen does not affect autoregulation in cat mesentery
Authors: Lang D. J. , Johnson P. C.
Published: December 2017

The purpose of this study was to determine whether oxygen plays a role in the autoregulation of blood flow in the isolated mesentery of the cat. Arteriolar diameter and red cell velocity were measured at normal arterial pressure and during 2 min of pressure reduction to 80 and 40 mmHg under ambient levels of 0, 10, and 20% oxygen in nitrogen. Autoregulatory responses during pressure reductions to 80 and 40 mmHg were not significantly different under 0% oxygen compared with those under 10 or 20% oxygen. Also, no significant difference was found in the control state between the mean diameters, linear velocities, or volume flows under 10 and 20% oxygen compared with 0% oxygen. We also determined oxygen levels just under the mesentery with different ambient oxygen levels. These values were the same as in the ambient gas mixture, suggesting that tissue oxygen levels in mesentery are determined by those in the external environment. Oxygen levels in the abdominal cavity averaged 67 mmHg, indicating that mesentery is normally exposed to a high-oxygen environment. We conclude that a change in tissue oxygen tension is not an essential factor in the mechanism of blood flow autoregulation in cat mesentery.
Synergistic effects of LTC4 and TxA2 on coronary flow and myocardial function
Authors: Nichols W. W. , Mehta J. L. , Thompson L. , Donnelly W. H.
Published: December 2017

Accumulation of leukocytes and platelets in the injured myocardium may influence coronary arteriolar resistance via release of peptidoleukotrienes and thromboxane A2 (TxA2). Although leukotriene C4 (LTC4) and TxA2 individually reduce coronary blood flow, the effects of their simultaneous administration are not known. Accordingly, the combined effects of intracoronary administration of synthetic LTC4 and thromboxane "mimic" U 46619 on coronary blood flow in patent and severely narrowed coronary arteries and myocardial segmental function were examined in eight anesthetized dogs. Administration of LTC4 and U 46619 (0.3-3 micrograms) showed concentration-dependent reductions in coronary blood flow and myocardial segment shortening. When these eicosanoids (3 micrograms each) were administered in close sequence, coronary blood flow decreased 33% in the patent artery and 47% in the narrowed artery. This reduction in coronary blood flow in the narrowed coronary artery produced a 26% decrease in myocardial segment shortening. Reductions in narrowed coronary artery blood flow and myocardial segment shortening were greater than the sum of changes caused by LTC4 and U 46619 administered separately (P less than 0.05). The histopathology of the narrowed coronary artery revealed endothelial disruption at the site of occlusion and an in vivo thrombus just distal to the site of occlusion. These data suggest marked synergism between the actions of LTC4 and TxA2, which may be released locally at the site of coronary thrombus, on blood flow in a severely narrowed coronary artery, and on segmental function in the region supplied by this vessel.
Effect of naloxone and ibuprofen on organ blood flow during endotoxic shock in pig
Authors: Nishijima M. K. , Breslow M. J. , Miller C. F. , Traystman R. J.
Published: December 2017

The effects of an opiate antagonist naloxone and a cyclooxygenase inhibitor ibuprofen on organ blood flow during endotoxic shock were evaluated in a fluid-resuscitated porcine endotoxic shock model. Radiolabeled microspheres were used to measure regional blood flow. Escherichia coli endotoxin (0.1 mg/kg), infused intravenously over 40 min, reduced mean arterial blood pressure to 50 mmHg and systemic vascular resistance to 57% of control without affecting cardiac output. Endotoxin reduced blood flow to cerebrum (to 49% of control), kidney (to 25% of control), spleen, and skeletal muscle, while blood flow to left ventricle, stomach, and small and large intestines were unaffected. Sixty minutes after endotoxin administration, animals were randomized to one of three groups. Group I animals were controls and received no drug, group II animals received ibuprofen (12.5 mg/kg iv), and group III animals received naloxone (2 mg/kg iv) 60 min after endotoxin. Ibuprofen increased mean arterial blood pressure to 80 mmHg and increased blood flow to both cerebrum (to 92% of control) and kidney (to 47% of control). Plasma levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha were increased 8- and 16-fold, respectively, after endotoxin, and both were decreased by ibuprofen. Naloxone increased mean arterial blood pressure to 62 mmHg but had no effect on regional blood flow or plasma cyclooxygenase metabolite levels. These data suggest that cyclooxygenase metabolites may contribute to decreased mean arterial blood pressure and reduced organ blood flow during endotoxic shock in the pig.
Hypoxanthine and lactate concentrations in lambs during hypoxic and stagnant hypoxia
Authors: Moss M. , Kurzner S. , Razlog Y. , Lister G.
Published: December 2017

To determine the suitability of plasma hypoxanthine as a marker of tissue hypoxia, we studied the relationship of arterial plasma hypoxanthine and blood lactate concentrations to the cumulative O2 deficit during hypoxemia and low cardiac output (hypoxic and stagnant hypoxia, respectively). Eight intact, chronically catheterized lambs were studied using ketamine sedation. Comparable reductions in O2 transport and consumption were produced with each form of hypoxia. Lactate was linearly related to O2 deficit during both forms of hypoxia, although the slope of the regression was greater for low cardiac output (0.049) than hypoxemia (0.032). Hypoxanthine was linearly related to cumulative O2 deficit only during low cardiac output. During hypoxemia, hypoxanthine concentration initially increased but plateaued with further increases in O2 deficit. The discrepancy in response of hypoxanthine was most likely caused by differences in the rate of elimination between stagnant and hypoxic hypoxia. We concluded that plasma hypoxanthine concentration was not a reliable marker for tissue hypoxia because it differed with the cause of O2 deprivation and did not necessarily reflect the severity of O2 deprivation.
Parathyroid hormone effects on skeletal exchangeable calcium and bone blood flow
Authors: Brindley G. W. , Williams E. A. , Bronk J. T. , Meadows T. H. , Montgomery R. J. , Smith S. R. , Kelly P. J.
Published: December 2017

The effects of alterations in serum calcium levels on the volume of distribution of a calcium tracer in bone and on bone blood flow were investigated in dogs by manipulation of parathyroid status. The volume of distribution increases with increasing serum calcium. This implies that there is a concentration-dependent binding mechanism in the extravascular space of bone, which is not saturated at the levels of serum calcium achieved in these experiments. The skeletal exchangeable calcium was increased in hypercalcemic dogs and decreased in hypocalcemic dogs. Cancellous bone contains proportionately more exchangeable calcium than cortical bone. Bone blood flow was decreased by 50% 15 min after injection of a bolus of parathyroid hormone (PTH) but returned to control values by 240 min. Fifty-two hours after the induction of hypercalcemia with repeated doses of PTH, there was no difference in blood flow over control animals.
STUDIES ON THE MECHANISM OF THE POTENTIATION OF CIRCULATORY EFFECTS OF HYPERTONIC SOLUTIONS RESULTING FROM ADMIXTURE OF THESE SOLUTIONS WITH HOMOLOGOUS BLOOD
Authors: Deyrup Ingrith J. , Walcott William W.
Published: December 2017

Page 510, line 20: The word "stimulate" should read "simulate." Page 512, line 38: The phrase, "345 mEq/l. (2% NaCl)," should read "345 mEq/l. (2%) NaCl." Page 514: Line 10 should read "... the spontaneous contractions being observed. In ten per cent of the tests, excitation was..." Page 518, line 11: For "possium ion" read "potassium ion."
Basal Blood Pressure of Normal Dogs Determined by an Auscultatory Method and a Study of the Effect of Fasting
Authors: Wilhelmj C. M. , Waldmann E. B. , McGuire T. F.
Published: December 2017

Page 299. C. M. Wilhelmj, E. B. Waldmann and T. F. McGuire, "Basal Blood Pressure of Normal Dogs Determined by an Auscultatory Method and a Study of the Effect of Fasting." In the footnote for table 2, the formula for the Standard Deviation should be as follows: (See PDF)
Reflex vasodilatation in the cat lip elicited by stimulation of nasal mucosa by chemical irritants
Authors: Izumi H. , Karita K.
Published: December 2017

Local application of capsaicin (threshold dose 150 microM) or nicotine (threshold dose 15 mM) to the nasal mucosa as well as electrical stimulation (threshold intensity 10 V) of the nasal mucosa elicited dose- or intensity-dependent blood flow increases in the ipsilateral lower lips of the anesthetized cats. Pretreatment with 3 mM capsaicin applied locally to the nasal mucosa abolished or reduced the vasodilation in response to capsaicin, nicotine, and ammonia vapor but not to light mechanical or electrical stimulation of the nasal mucosa. The blood flow increases elicited by all above stimuli were greatly reduced by pretreatment with hexamethonium, an autonomic ganglion blocker. These results suggest that stimulation of the nasal mucosa by chemical (capsaicin, nicotine, ammonia), mechanical, or electrical methods elicits the autonomic reflex vasodilatation in the cat lower lips. Furthermore, there seem to be at least two types of afferent fibers in the nasal mucosa of the cats: one type is capsaicin-sensitive fibers, while another type is capsaicin-resistant fibers involved in reflex vasodilatation.
Development of meadow voles is influenced postnatally by maternal photoperiodic history
Authors: Lee T. M.
Published: December 2017

The importance of maternal photoperiodic history during lactation on the postnatal development of meadow vole pups was tested by cross-fostering pups on the day of birth between photorefractory females (housed for 26 wk in a 10:14-h light-dark cycle before mating) and photosensitive females (housed for 2 wk in a 10:14-h light-dark cycle before mating). Control pups were cross-fostered to females with the same photoperiodic history as the gestational dam. Somatic growth and food intake of cross-fostered pups were influenced by the photoperiod of the postnatal lactating dam. Pre- and postnatal maternal photoperiodic history interacted with the sex of the offspring to influence reproductive development. Pelage development was determined exclusively by the prenatal maternal photoperiodic history. The impact of a postnatal maternal influence on pup development of photoperiod-sensitive traits is discussed.
Renal response to atrial stretch during pregnancy in conscious rats
Authors: Kaufman S. , Deng Y.
Published: December 2017

Chronic indwelling balloons were placed at the junction of the right atrium and the right superior vena cava of virgin female rats. The renal response to discrete standardized atrial stretch was tested in the conscious animals. The rats were then mated, and the renal response was retested at days 7, 14, and 20 of pregnancy. On day 21, the rats were killed, and the pressure-volume relationship of the right atria was measured. In response to atrial stretch, there was an increase in urine volume, urine sodium output, and urine potassium output and a decrease in free water clearance in the virgin rats. Subsequent to mating, these responses were completely abolished at all stages of pregnancy. The renal responses to atrial stretch were also abolished during pseudopregnancy. Central venous pressure did not change when the intracardiac balloons were inflated; there were also no changes in resting central venous pressure during pregnancy. There were no significant changes in unstressed atrial volume or in atrial compliance during pregnancy.
Alpha 2-adrenoceptor-mediated inhibition of bulbospinal barosensitive cells of rat rostral medulla
Authors: Allen A. M. , Guyenet P. G.
Published: December 2017

Bulbospinal barosensitive neurons of the rostral ventrolateral medulla (RVLM cells; presumed sympathetic vasomotor premotor neurons) were recorded with iontophoretic electrodes in urethan-anesthetized rats. The majority of these cells were insensitive to intravenous clonidine (Clo; up to 20 micrograms/kg) and insensitive to iontophoretically applied Clo or alpha-methylnorepinephrine (alpha-MNE). These cells (n = 47 of 76) had a spinal conduction velocity of 4.1 +/- 0.2 m/s and a mean firing rate of 20 +/- 1 spikes/s. A second population (n = 29) was powerfully inhibited by intravenous Clo (5-10 micrograms/kg, activity decreased by 83 +/- 11%), iontophoretically applied Clo (decreased by 51 +/- 7%), and iontophoresis of alpha-MNE (decreased by 69 +/- 3%). These cells had a slower conduction velocity (2.0 +/- 0.3 m/s) and a much slower discharge rate (6 +/- 1 spikes/s). Both populations were pulse synchronous at resting arterial pressure. The inhibitory effects produced by iontophoresis of alpha-MNE or Clo were reduced to the same degree (86-98%) by iontophoresis of idazoxan (an alpha 2-adrenergic antagonist with imidazoline structure) and by iontophoresis of piperoxan (65-77%, a nonimidazoline alpha 2-antagonist). The inhibition of RVLM cells by intravenous Clo was reversed by iontophoresis of idazoxan and by intravenous injection of yohimbine (nonimidazoline alpha 2-antagonists). These data suggest that 1) intravenous Clo only inhibits a subpopulation of RVLM sympathetic premotoneurons, possibly the C1 adrenergic cells, 2) this effect of Clo is due to activation of alpha 2-adrenergic receptors rather than nonadrenergic imidazoline binding sites, and 3) these alpha 2-receptors are located on or close to the Clo-sensitive cells and may be continuously activated by endogenously released catecholamines.
Characterization of baroreflex impairment in conscious dogs with pacing-induced heart failure
Authors: Olivier N. B. , Stephenson R. B.
Published: December 2017

Open-loop baroreflex responses were evaluated in eight conscious dogs before and during congestive heart failure to determine the effects of failure on baroreflex control of blood pressure, heart rate, cardiac output, and total peripheral resistance. Heart failure was induced by rapid ventricular pacing. Baroreflex function was determined by calculation of the range and gain of the open-loop stimulus-response relationships for the effect of carotid sinus pressure on blood pressure, heart rate, cardiac output, and total peripheral resistance. The range and gain of blood pressure responses were substantially reduced as early as 3 days after induction of heart failure (161 +/- 6 to 99 +/- 8 mmHg and -2.7 +/- 0.3 to -1.5 +/- 0.1, respectively) and remained depressed for the 21 days of heart failure. This depression in baroreflex control of blood pressure was associated with similar depressions in reflex range and gain for heart rate (125 +/- 9 to 78 +/- 11 beats/min and -2.05 +/- 0.2 to -1.16 +/- 0.2 beats/min, respectively) and cardiac output (1.74 +/- 0.2 to 0.46 +/- 0.2 l/min and -0.81 +/- 0.02 to -0.027 +/- 0.008 l/min, respectively). The group-averaged range and gain for reflex control of vascular resistance were not altered by heart failure. In three dogs, discontinuation of rapid ventricular pacing led to resolution of heart failure within 7 days and partial restoration of the range and gain of reflex control of blood pressure. We conclude that heart failure reversibly depresses baroreflex control of blood pressure principally through a concurrent reduction in reflex control of cardiac output, whereas reflex control of vascular resistance is not consistently affected.
Fever and thermogenesis in response to bacterial endotoxin involve macrophage-dependent mechanisms in rats
Authors: Derijk R. H. , Strijbos P. J. , van Rooijen N. , Rothwell N. J. , Berkenbosch F.
Published: December 2017

Increases in thermogenesis and body temperature (fever) frequently accompany infection or injury and are thought to be mediated by endogenous pyrogens (e.g. cytokines), which are released from activated immune cells such as macrophages. Therefore, we have investigated the effect of selective elimination of peripheral macrophages on the changes in oxygen consumption (VO2) and colonic temperature in response to bacterial lipopolysaccharide (LPS) in the rat. Peripheral macrophages were depleted by intravenous injection of liposomes containing the drug dichloromethylene diphosphonate (Cl2MDP). Resting oxygen consumption and colonic temperatures were not affected by macrophage elimination. In intact rats, peripheral injection of LPS (0.1-0.5 mg/kg) elicited an increase in colonic temperature and in oxygen consumption that declined at higher doses (2.5 mg/kg). The pyrogenic and thermogenic responses to LPS were significantly attenuated in rats in which peripheral macrophages were eliminated. Previously, we have reported that elimination of macrophages blunts the plasma interleukin-1 (IL-1) response to LPS. Here we show that elimination of macrophages does not affect the increase in plasma IL-6 concentrations in response to LPS. These data indicate that the pyrogenic and thermogenic responses to LPS are at least in part dependent on mechanisms involving peripheral macrophages, and that peripherally produced IL-1 rather than IL-6 may be an important mediator of the changes in oxygen consumption and colonic temperature in response to LPS.
Volume-activated K+ and Cl- pathways of dissociated eccrine clear cells
Authors: Samman G. , Ohtsuyama M. , Sato F. , Sato K.
Published: December 2017

In isolated rhesus eccrine clear cells, regulatory volume decrease (RVD) occurs after osmotic swelling. RVD was completely inhibited by 1 mM quinidine, 200 nM charybdotoxin, 1 mM diphenylamine-2-carboxylic acid (DPC), or 0.1 mM 4-nitro-2(3-phenylpropyl-amino)benzoate. RVD was also inhibited in Ca(2+)-free medium by vinblastine (antimicrotubular agent), N-(6-aminohexyl)-5-chloro-1- naphthalenesulfonamide (W-7), or 0.1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Valinomycin reversed quinidine- and DIDS-induced inhibition of RVD but not the inhibition caused by Ca(2+)-free medium, DPC, vinblastine, or W-7. The cytosolic free Ca2+ concentration, as determined by the fura 2 method, increased from 220 nM in the control to 435 nM during RVD. Activation of both K+ and Cl-currents was also directly demonstrated with the whole cell current-voltage clamp method. DIDS inhibited swelling-induced K+, but not Cl-, currents and depolarized the membrane potential during RVD, further supporting the notion that DIDS inhibited swelling-activated K+, but not Cl-, pathways. We conclude that the observed RVD is mediated by the activation of conductive Ca(2+)-dependent K+ and Cl- pathways.
Effects of glucose infusion on hormone secretion and hepatic glucose production during heavy exercise
Authors: Wiersma M. M. , Vissing J. , Steffens A. B. , Galbo H.
Published: December 2017

Blood-borne metabolic feedback vs. neural feedforward regulation of glucose homeostasis during exercise was investigated by infusion glucose and [3H]glucose for glucose appearance determination intravenously in rats running for 20 min at 28 m/min [approximately 85% of maximal O2 consumption (VO2max)]. Infused glucose corresponded to the exercise-induced increase in hepatic glucose production (HGP) found in saline-infused rats. Saline- and glucose-infused resting rats were also studied. Arterial blood was sampled for analyses of hormones and metabolites. Plasma epinephrine, norepinephrine, and insulin were always similar and HGP was initially similar in the two exercising groups, although glucose infusion resulted in higher plasma glucose compared with control (P < 0.05). Late during exercise, high plasma glucose (11.3 +/- 0.4 vs. 9.6 +/- 0.3 mM) and low glucagon (16 +/- 2 vs. 27 +/- 3 pM) in glucose- vs. saline-infused rats caused an inhibition of HGP in glucose-infused rats, although never below preexercise levels. In resting rats, glucose infusion resulted in elevated plasma glucose and insulin and, in turn, inhibition of HGP but had no effect on catecholamines, corticosterone, or glucagon. The findings indicate that during heavy exercise, glucose homeostasis is regulated primarily by neural feedforward mechanisms and that blood-borne metabolic feedback mechanisms play a regulatory role if metabolic error signals are pronounced.
Tumor necrosis factor is not involved in exercise-induced elevation in core temperature
Authors: Rowsey P. J. , Borer K. T. , Kluger M. J.
Published: December 2017

Female Sprague-Dawley rats (12:12-h light-dark photoperiod) with access to running wheels have an elevated body temperature (BT) both during exercise (nighttime) and nonexercise periods (daytime). We studied whether the exercise-induced increase in BT is modulated by the release of the cytokine, tumor necrosis factor-alpha (TNF). Two weeks after the onset of exercise, nighttime temperatures of exercising rats were elevated approximately 0.5 degree C compared with preexercise values (P = 0.006). By 3 wk after the onset of exercise, daytime temperatures had increased 0.3 degree C (P = 0.03) above control levels. To confirm that endogenously produced TNF can modulate fever in female rats, we injected six rats with antiserum to TNF (300 microliters/rat) and six rats with control serum 24 h before intraperitoneal injection of lipopolysaccharide (50 micrograms/kg). As occurred in earlier studies on male rats, antiserum-treated female rats had significantly enhanced fevers (P = 0.017). To determine whether endogenously produced TNF was involved in modulating the daytime and nighttime increases in BT, antiserum to TNF (300 microliters/rat, n = 7) or control serum (300 microliters/rat, n = 5) was injected intraperitoneally in exercising rats. Neither injection of antiserum nor control serum had any effect on daytime or nighttime BTs. Because BTs of exercising female rats injected with antiserum against TNF were not affected, we conclude that TNF is not responsible for modulating their exercise-induced rise in BT.
Parenteral nutrition, brain glycogen, and food intake
Authors: Meguid M. M. , Beverly J. L. , Yang Z. J. , Gleason J. R. , Meguid R. A. , Yue M. X.
Published: December 2017

To determine whether brain glycogen concentrations change during parenteral nutrition, Fischer 344 rats with jugular vein catheters received 0.9 N saline or parenteral nutrition providing 100% of daily calories (PN-100). Rats were killed after 4 days of PN-100 and serially after PN-100 was stopped. Food intake decreased during PN-100 to approximately 15% of control, but total kilocalories eaten and infused over the 4-day PN-100 period was approximately 130% of control. Food intake of PN-100 rats remained low for 3-4 days post-PN-100. At the end of the 4-day PN-100 period, plasma glucose and insulin (P = 0.01) and whole brain glycogen (P < 0.005) were higher than but similar to control within 24 h of PN-100 being stopped. When PN-100 rats were not allowed to eat during the infusion period, plasma glucose was lower, plasma insulin higher, and brain glycogen content the same as in control rats after 4 days of PN-100. The increased brain glycogen was the likely consequence of the hyperglycemia and hyperinsulinemia during PN-100 and was not causally associated with the reduced food intake either during or immediately after PN-100.
Hepatic phosphate trapping, decreased ATP, and increased feeding after 2,5-anhydro-D-mannitol
Authors: Rawson N. E. , Blum H. , Osbakken M. D. , Friedman M. I.
Published: December 2017

The mechanism by which the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) elicits feeding behavior was investigated by studying its metabolism and biochemical effects in liver. Thin-layer chromatography of liver extracts from rats given 2,5-AM containing 14C-labeled 2,5-AM showed that the analogue is phosphorylated in vivo with a time course that parallels the eating response. In vivo 31P nuclear magnetic resonance spectroscopy of rat liver during intravenous infusion of 2,5-AM and high-resolution nuclear magnetic resonance analyses of liver extracts showed that 2,5-AM is rapidly phosphorylated in liver, trapping hepatic phosphate and decreasing ATP, inorganic phosphate, and phosphate diesters. These changes occurred in a time frame in which the feeding response is elicited in conscious animals given the same dose of 2,5-AM by the same route. During an interval in which 2,5-AM increased eating, it also increased urinary uric acid excretion, implicating enhanced adenosine degradation in the reduction in hepatic ATP. These results provide the first direct evidence that changes in a high-energy phosphate-carrying compound in liver may provide a signal to initiate eating behavior.
Lipopolysaccharide induces fever and depresses locomotor activity in unrestrained mice
Authors: Kozak W. , Conn C. A. , Kluger M. J.
Published: December 2017

The purpose of this study was to characterize the basic biology of fever to lipopolysaccharide (LPS) in unrestrained mice. Although LPS has been shown to induce fevers in many laboratory animals (e.g., rats, guinea pigs, rabbits), there is some question of whether LPS causes a fall or rise in body temperature (Tb) in mice. Tb was measured by biotelemetry in unrestrained mice maintained at an ambient temperature of 30 degrees C. Intraperitoneal injections of LPS at doses of 1.0, 2.5, and 3.0 mg/kg induced dose-independent prompt decreases of Tb for 5.7 h. After this postinjection reduction, Tb increased and reached a peak at approximately 24 h postinjection. The peak rises in Tb were dose dependent. Changes in Tb due to LPS were accompanied by suppression of locomotor activity. Indomethacin, at a dose that did not affect normal Tb, enhanced the temperature-lowering effect of LPS as well as inhibited the febrile rise of Tb after LPS. Indomethacin did not modify the reduction in activity caused by the injections of LPS. Food intake of the mice was decreased by LPS in a dose-dependent manner, and tolerance developed to a second injection of LPS. We conclude that freely moving mice can develop pronounced and reproducible fevers in response to LPS, which is different in time course, dose-dependent profile, induction of pyrogenic tolerance profile, and mode of inhibition by indomethacin from those responses that have been observed in other species studied so far.
Corticotropin responses to hypoglycemia and hypotension during ovine pregnancy
Authors: Keller-Wood M.
Published: December 2017

The adrenocorticotropic hormone (ACTH) responses to hypoglycemia and to hypotension were compared in pregnant and nonpregnant ewes. In the first study pregnant and nonpregnant ewes were each subjected to hypoglycemia induced by injection of 0.05, 0.10, or 0.25 U regular insulin/kg body wt or to saline infused as a control. In the second study pregnant and nonpregnant ewes were subjected to hypotension induced by the infusion of 2.5, 5.0, or 10.0 micrograms nitroprusside.kg-1.min-1 or to dextrose infused as a control. ACTH responses to hypoglycemia were significantly increased in the pregnant ewes, and the relation between plasma glucose and plasma ACTH was shifted to the right, indicating greater ACTH responses for a given level of hypoglycemia in the pregnant state. The mean ACTH response to infusion of nitroprusside was reduced during pregnancy, despite significantly lower mean arterial blood pressure in the pregnant ewes. When the relation between mean arterial pressure and ACTH was compared in the two groups of ewes, the relation was significantly shifted to the left in the pregnant ewes, indicating lower ACTH responses to a given level of pressure during pregnancy. The results suggest that pregnancy does not uniformly alter ACTH responses to stimuli, suggesting multiple, stimulus-specific effects of pregnancy on the hypothalamo-pituitary-adrenal axis.
Modulation of rate at which serotonin-induced contraction decays in guinea pig trachea
Authors: Ben-Harari R. R. , Dalton B. A. , Garg U. C.
Published: December 2017

Stimulation of the type 2 serotonin (5-HT2) receptor in guinea pig trachea with 5-HT results in a contraction that decays in the continued presence of 5-HT. The decay of the 5-HT contraction has been proposed to be dependent on 5-HT2 receptor activation and to reflect desensitization of the receptor. The characteristics of the decay of the 5-HT contraction may also be dependent on other properties of the tissue. The effects of modulation of biochemical pathways implicated in airway smooth muscle contraction on the 5-HT contraction in isolated guinea pig trachea were determined with the use of a kinetic approach we developed previously. Decay of the 5-HT contraction was inhibited by cooling, increased by forskolin, 3-isobutylmethyl-1-xanthine, and 8-bromoadenosine 3',5'-cyclic monophosphate, and unaffected by staurosporine, H-7, H-8, phorbol 12,13-dibutyrate, and by inhibitors of the three major pathways of arachidonic metabolism. The results suggest that decay of the 5-HT contraction in guinea pig trachea is dependent on both the receptor and the biochemical state of the tissue.
Processing of splanchnic and somatic input in thoracic spinal cord of the rat
Authors: Akeyson E. W. , Schramm L. P.
Published: December 2017

To better understand the spinal transmission of visceral afferent information, we conducted neurophysiological studies of single spinal neurons that receive input from the greater splanchnic nerve (GSN). Extracellular single-neuron recordings were made in the thoracic spinal cord of chloralose-anesthetized, paralyzed, and artificially ventilated rats, some of which had undergone acute spinal transection at C1. Neurons were divided into four classes according to their responses to GSN stimulation: one-burst excitatory, two-burst excitatory, biphasic, and inhibited. We then studied the characteristics of the convergent somatic input to each class of neurons using either natural somatic stimuli or electrical stimulation of the iliohypogastric nerve (IHN). Most splanchnic input was mediated by unmyelinated fibers, whereas somatic input was mediated by both unmyelinated and small myelinated fibers. Most of the neurons exhibited somatic receptive fields, and the majority responded to both innocuous and noxious somatic stimuli. However, a small number could be excited only by GSN stimulation. Although a careful analysis of response characteristics indicated that there was a tendency for neurons to exhibit similar responses to electrical stimulation of the GSN and the IHN, we observed many combinations of somatic and visceral responses. We suggest that visceral afferent activity, in addition to being processed via convergent somatovisceral pathways, may be processed by neurons that convey only visceral information or by neurons in which visceral and somatic information is differentially coded.
Splanchnic and somatic afferent convergence on cervical spinal neurons of the rat
Authors: Akeyson E. W. , Schramm L. P.
Published: December 2017

The rostral cervical spinal cord is increasingly being considered the source of important propriospinal regulation. To better understand the substrate for this function, we investigated the effects of stimulation of the greater splanchnic nerve (GSN) and both thoracic and cervical somatic afferents on the activity of cervical spinal neurons. Extracellular single-neuron recordings were made in the C2-C5 spinal segments of chloralose-anesthetized, paralyzed, and artificially ventilated rats. Neurons were classified according to their responses to GSN stimulation. Neurons were inhibited by this stimulation as frequently as they were excited. We then studied the characteristics of cervical and thoracic convergent somatic input to each class of neurons. Although all cervical neurons that responded to GSN stimulation responded to electrical stimulation of the iliohypogastric nerve (IHN), only the few neurons that exhibited whole body receptive fields (RF) responded to natural thoracic somatic stimuli. Responses to electrical stimulation of the GSN and IHN were similar for most neurons; most exhibited nociceptive cutaneous RFs in cervical dermatomes. These data indicate that input from cervical somatic afferents and from both thoracic visceral and thoracic somatic afferents converge on individual splanchnic-receptive cervical neurons. Although these neurons exhibited the predicted cervical somatic RFs, responses from thoracic levels did not exhibit discrete RFs, requiring instead more synchronous or more spatially convergent input.
Role of serotonin and catecholamines in sympathetic responses evoked by stimulation of rostral medulla
Authors: Huangfu D. , Hwang L. J. , Riley T. A. , Guyenet P. G.
Published: December 2017

In halothane-anesthetized, paralyzed rats, single-pulse stimulation of nucleus raphe pallidus/obscurus (NR) evoked an inhibition followed by a single wave of excitation in 1) the mass discharge of lumbar and splanchnic sympathetic nerves (modal onset latencies: LSND 210 +/- 14 ms, SSND 161 +/- 5 ms) and 2) the unit activity of lumbar sympathetic vasoconstrictor neurons (LSVNs). Stimulation of the rostral ventrolateral medulla (RVL) produced two excitatory responses in LSND, SSND, and LSVN units (modal onset latencies: RVL peak I 98 +/- 8 ms for LSND and 62 +/- 2 ms for SSND; RVL peak II 210 +/- 15 ms for LSND and 160 +/- 6 ms for SSND). Most LSVNs received excitatory inputs from both raphe and RVL. NR peak was selectively attenuated (76%) by 5,7-dihydroxytryptamine [intracisternally (ic), 2-wk] and acute intrathecal (it) methiothepine (10 micrograms, 69%) or methysergide (40 micrograms, 72%). 6-Hydroxydopamine (2-wk ic) produced no effect. Phentolamine (20 micrograms it) or prazosin (20 micrograms it) reduced RVL peak II by > 94% and attenuated NR peak (phentolamine 67%, prazosin 46%). Intrathecal kynurenic acid produced proportionately larger reduction of RVL peak I than raphe peak or RVL peak II. Our interpretations are 1) LSVNs receive convergent excitatory inputs from midline raphe, parphyramidal area, and RVL, 2) bulbospinal serotonergic neurons mediate most of the sympathoexcitation evoked from NR and a portion of RVL peak II, 3) a catecholamine probably released by C1 cells mediates most of RVL peak II and a portion of the NR response, and 4) RVL peak I is predominantly mediated by an excitatory amino acid.
Renin-angiotensin, arterial blood pressure, and salt appetite in rats
Authors: Thunhorst R. L. , Johnson A. K.
Published: December 2017

Simultaneous administration of the diuretic furosemide (10 mg/kg sc) and a low dose of the angiotensin-converting enzyme inhibitor captopril (5 mg/kg sc) reduced mean arterial blood pressure (MAP) and increased ingestion of water and 0.3 M NaCl within 2 h. Administration of either agent alone did not reduce MAP or cause significant fluid intakes. The increased ingestion of water and saline after furosemide plus captopril 1) was not due to increased excretion of water and sodium compared with losses after furosemide alone, 2) was abolished by the AT1-receptor blocker, losartan (10 mg/kg sc), and 3) was abolished by administration of a greater dose of captopril (100 mg/kg sc). Intravenous infusion of phenylephrine (3-4 micrograms.kg-1 x min-1) prevented the reduction in MAP after furosemide plus captopril and blunted the saline intake but not water intake. Simultaneous administration of the vasodilator minoxidil and captopril also stimulated robust salt appetite in association with reduced MAP. It is concluded that the integrity of renin-angiotensin mechanisms is necessary for the rapid ingestion of water and saline after furosemide and captopril and that arterial pressure modulates the behavioral responses.
Gustatory deafferentation and desalivation: effects on NaCl preference of Fischer 344 rats
Authors: Sollars S. I. , Bernstein I. L.
Published: December 2017

The chorda tympani nerve (CT) appears to be particularly responsive to NaCl stimulation of the tongue. However, in most strains of rat, bilateral transection of the CT (CTX) results in little alteration of salt preference. The Fischer 344 (F344) strain of rat is unusual in its lack of preference for any concentration of salt. We recently reported a dramatic change from aversion to preference for salt in F344 rats after CTX. The present studies further explored this alteration in salt preference of F344 rats with an expanded range of NaCl concentrations. Additionally, the specificity of the CT in mediating F344 salt aversion was examined by testing NaCl preference after glossopharyngeal nerve (GL) transections, combined CT and GL deafferentation, and partial desalivation. Comparison with Wistar rats revealed that salt preference of F344 CTX rats followed a typical preference/aversion pattern across a range of NaCl concentrations. Studies of GL section, either alone or combined with CT sectioning, indicated that F344 rats' aversion was dependent on the integrity of the CT and not the GL. Removal of sublingual and submaxillary salivary glands did not lead to preference changes similar to those after CTX, indicating that the effects of CTX are not secondary to desalivation. Overall, the findings point to signals from the CT as playing a primary role in the NaCl aversion displayed by the intact F344 rat.
Nitro-L-arginine attenuates hypercapnic cerebrovasodilation without affecting cerebral metabolism
Authors: Iadecola C. , Xu X.
Published: December 2017

We have previously demonstrated that topical cortical application of nitro-L-arginine (L-NA), a potent inhibitor of nitric oxide (NO) synthesis, attenuates resting cerebral blood flow (CBF) and the cerebrovasodilation elicited by hypercapnia. In this study, we sought to determine whether these cerebrovascular effects of L-NA are secondary to a depression in cerebral metabolism. Rats were anesthetized (chloralose, 80 mg/kg) and artificially ventilated. Arterial pressure and blood gases were monitored. The frontal cortex was exposed and superfused with normal Ringer (pH 7.3-7.4; 37 degrees C) or with Ringer containing L- or D-NA. CBF or cerebral glucose utilization (CGU) was measured autoradiographically using the [14C]iodoantipyrine or 2-[14C]deoxy-D-glucose method, respectively. Application of normal Ringer did not affect CBF at the site of superfusion (n = 5; P > 0.05, paired t test). Application of L-NA (1 mM; n = 5), but not D-NA (1 mM; n = 6), attenuated resting CBF by 33 +/- 5% (P < 0.05; analysis of variance). During hypercapnia (partial pressure of CO2 = 55-60 mmHg), L-NA attenuated the CBF increase by 78 +/- 6% (n = 5/group; P < 0.05 from Ringer), whereas D-NA had no effect (P > 0.05). Resting CBF and the CBF response to hypercapnia were largely unaffected in brain regions outside the field of superfusion. In contrast to hypercapnia, L-NA (1 mM) did not attenuate the increases in CBF elicited by topical application of papaverine (10-1,000 microM; n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)
Lesions of hypothalamic PVN partially attenuate stimulatory action of alcohol on ACTH secretion in rats
Authors: Rivest S. , Rivier C.
Published: December 2017

We have previously shown that the ability of alcohol to stimulate adrenocorticotropic hormone (ACTH) secretion was significantly blunted by immunoneutralization of endogenous corticotropin-releasing factor (CRF) and that long-term exposure to alcohol increased CRF mRNA levels in the paraventricular nucleus (PVN) of the hypothalamus. In the present study, we further investigated the participating role of the PVN by studying the effect of bilateral lesions of the PVN on alcohol-induced ACTH release. The acute injection of alcohol (1.5 g/kg ip) induced significant increases in plasma ACTH levels in sham-operated animals. Lesions of the PVN attenuated this response but did not abolish it. Indeed, lesioned rats retained significantly elevated ACTH values despite removal of secretagogues of PVN origin. Because removal of hypothalamic CRF can alter ACTH secretion in response to secretagogues, we studied possible changes in pituitary responsiveness to CRF. The results failed to indicate that hyperresponsiveness of the corticotrophs played a major role in accounting for the residual ACTH release of lesioned rats after alcohol treatment. We conclude that brain regions other than the PVN can modulate ACTH release during acute administration of alcohol.
Orally administered L-arginine does not alter right ventricular hypertrophy in chronically hypoxic rats
Authors: Resta T. C. , Walker B. R.
Published: December 2017

Evidence suggests that nitric oxide synthesis within the pulmonary circulation may be attenuated during chronic hypoxia in Wistar rats due to reduced L-arginine availability. In contrast, chronically hypoxic Sprague-Dawley rats exhibit normal endothelium-dependent pulmonary vasodilation. The purpose of the present study was to determine whether 1) Wistar rats demonstrate greater right ventricular (RV) hypertrophy in response to chronic hypoxia than Sprague-Dawley rats and 2) chronic administration of L-arginine would diminish this response in Wistar rats. L-Arginine had no effect on the degree of hypoxia-induced RV hypertrophy or polycythemia in either strain of rat. However, Wistar rats demonstrated greater hypoxia-induced RV hypertrophy and polycythemia compared with Sprague-Dawley rats. To determine whether chronically hypoxic Wistar rats indeed exhibit impaired endothelium-dependent pulmonary vasodilation, isolated lungs from control and chronically hypoxic Wistar rats were administered the endothelium-dependent pulmonary vasodilators A23187 or vasopressin. Vasodilatory responses to either agent were unaffected by chronic hypoxic exposure. We conclude that endothelium-dependent pulmonary vasodilation is maintained in the pulmonary circulation of chronically hypoxic Wistar and Sprague-Dawley rats.
Endogenous opioids are differentially involved in appetitive and consummatory aspects of sexual behavior of male rats
Authors: Van Furth W. R. , Wolterink-Donselaar I. G. , van Ree J. M.
Published: December 2017

The sexual activity of 40 male Wistar rats was tested weekly in a bilevel test chamber to evaluate the involvement of endogenous opioids in the appetitive and consummatory aspects of sexual behavior. It has been suggested that the increase of the anticipatory level-changing behavior over repeated testing, displayed before the introduction of a receptive female, is sexually motivated. Two doses of the opioid antagonist naloxone, 1 and 10 mg/kg, prevented the increase of the anticipatory level-changing over four repeated tests of sexually experienced rats without prior experience in the bilevel test chamber and decreased the number of level changes of rats displaying a high number of level changes. Analysis of the pattern of inhibition suggested that the lower dose of naloxone may reduce sexual reward and that, in addition, the higher dose may block the expression of motivation. In contrast, naloxone treatment facilitated the efficiency of the sexual performance, with less mounts and intromissions preceding ejaculation and a shorter ejaculation latency, implying an inhibitory role of endogenous opioids in the neural control of some aspects of sexual performance (e.g., ejaculatory threshold). These results suggest that endogenous opioids may increase sexual appetite and diminish sexual performance.
Allometry of muscle, tendon, and elastic energy storage capacity in mammals
Authors: Pollock C. M. , Shadwick R. E.
Published: December 2017

This paper considers the structural properties of muscle-tendon units in the hindlimbs of mammals as a function of body mass. Morphometric analysis of the ankle extensors, digital flexors, and digital extensors from 35 quadrupedal species, ranging in body mass from 0.04 to 545 kg, was carried out. Tendon dimensions scale nearly isometrically, as does muscle mass. The negative allometry of muscle fiber length results in positive allometric scaling of muscle cross-sectional areas in all but digital extensors. Maximum muscle forces are predicted to increase allometrically, with mass exponents as high as 0.91 in the plantaris, but nearly isometrically (0.69) in the digital extensors. Thus the maximum amount of stress a tendon may experience in vivo, as indicated by the ratio of muscle and tendon cross-sectional areas, increases with body mass in digital flexors and ankle extensors. Consequently, the capacity for elastic energy storage scales with positive allometry in these tendons but is isometric in the digital extensors, which probably do not function as springs in normal locomotion. These results suggest that the springlike tendons of large mammals can potentially store more elastic strain energy than those of smaller mammals because their disproportionately stronger muscles can impose higher tendon stresses.
Lack of effect of ouabain on calcium homeostasis in rat platelets: comparative study with human platelets
Authors: Oshima T. , Ishida T. , Matsuura H. , Ishida M. , Ishibashi K. , Ozono R. , Watanabe M. , Kajiyama G. , Kanbe M.
Published: December 2017

The precise mechanisms of Ca2+ handling in rat platelets are not fully understood. We sought to determine whether rat platelets possess a Na(+)-Ca2+ exchanger. First, we investigated the time course of the effect of ouabain (10(-4) M) on cytosolic sodium concentration ([Na+]i) and Ca2+ homeostasis in platelets from Wistar rats in comparison with those from humans. Ouabain increased platelet [Na+]i in both rat and human platelets. Whereas ouabain induced a time-dependent increase in basal and thrombin-stimulated (0.3 units/ml) cytosolic calcium concentration ([Ca2+]i) in human platelets, no change was found in rat platelets. Furthermore, 90-min pretreatment of rat platelets with ouabain did not affect the [Ca2+]i response to thrombin (0.1-1.0 units/ml) or a maximal dose of ionomycin (5 microM). Also the decline in [Ca2+]i after the peak response evoked by these agonists in the absence of extracellular Ca2+ was not changed by ouabain pretreatment. Similarly, replacement of extracellular Na+ had no influence on any of these determinations. Thus decreasing the plasma membrane Na+ gradient did not affect basal [Ca2+]i, thrombin-induced mobilization of Ca2+ from intracellular stores, internal Ca2+ discharge capacity, or Ca2+ extrusion from cytosol of rat platelets. In contrast to human platelets, a Na(+)-Ca2+ exchange mechanism does not appear to play a significant role in Ca2+ homeostasis of rat platelets.