bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of variable caloric restriction on utilization of ingested energy in rats
Authors: Hill J. O. , Latiff A. , DiGirolamo M.
Published: December 2017

Body weight reductions were produced in five groups of male Wistar rats (325 g) by starvation or by variable degrees of underfeeding. The resulting body weights were maintained, by adjusting daily food intake, at constant levels for at least 18 days. We found that 1) energy conservation (i.e., a reduction in the amount of energy required for maintenance) developed in proportion to reduction in body weight, 2) energy conservation increased even while reduced body weights were maintained at constant levels, 3) reduction in the energy required for maintenance was largely due to reduced resting metabolic rate, 4) a maximal ability to conserve energy seemed to occur in severely food-restricted rats, and 5) the magnitude of energy conservation appeared to be proportional to the absolute reduction in body weight and was unrelated (in the long run) to rapidity of weight loss. This study confirms that precise mechanisms of energy conservation are set in motion by food restriction and attempts to identify some components of this adaptive response.
Temperature regulation in lizards: effects of hypoxia
Authors: Hicks J. W. , Wood S. C.
Published: December 2017

Temperature regulation during external (lowered lung PO2) and internal hypoxia (anemia) was examined in four species of lizards. Exposure to a hypoxic gas mixture in a thermogradient resulted in the animals lowering their selected (preferred) body temperature. A 50% reduction in the O2 carrying capacity of the blood also reduced the selected body temperature. Lizards "shuttle" when forced to select a temperature either above or below their normal selected temperature. Exposure to hypoxia decreases the upper and lower exit temperatures during shuttling. Furthermore, a decrease in the inspired O2 causes the rate of heating to no longer exceed the rate of cooling as is normal. The behavioral reduction of body temperature and the altered neural and physiological aspects of temperature regulation appear to be generalized responses to impaired O2 transport and not PO2 per se. The reduced body temperature, by lowering metabolic demand, provides an effective, even life-saving, adaptation to hypoxia.
Acetoacetate and 3-hydroxybutyrate kinetics in obese and insulin-dependent diabetic humans
Authors: Nosadini R. , Avogaro A. , Trevisan R. , Duner E. , Marescotti C. , Iori E. , Cobelli C. , Toffolo G.
Published: December 2017

[3-14C]acetoacetate (AcAc) and beta-[3-14C]hydroxybutyrate (beta-OHB) administration, measurements of labeled AcAc and beta-OHB in blood, and kinetic modeling have been used to investigate ketone body (KB) metabolism in five normal, five obese, and eight insulin-withdrawn diabetic subjects. Diabetic subjects were divided in mildly ketotic (MKD) and highly ketotic (HKD) patients according to beta-OHB blood level. A four-compartmental model successfully described the tracer kinetic data in obese and normal subjects, whereas in diabetic patients a five-compartmental model was necessary. Obese subjects showed a significantly lower (P less than 0.05) KB de novo synthesis (R30 = 159 +/- 54 (SD) mumol X min-1 X m-2) in comparison with normal subjects (282 +/- 93), but the clearance rates of AcAc (PCR1) and beta-OHB (PCR2) were similar in the two groups. R30 was 596 +/- 534 in MKD and 1,278 +/- 445 (P less than 0.01) in HKD. PCR1 was not significantly different both in MKD and HKD in comparison with normal subjects. In contrast PCR2 was markedly reduced in HKD (0 +/- 0 ml X min-1 X m-2) in comparison with MKD (1,031 +/- 615) and normal subjects (782 +/- 278). The percentage distribution of KB among various tissues inside the organism of diabetic subjects is abnormal. Both AcAc and beta-OHB recycling and mean residence time are not normal in HKD. A significant correlation was found between C-peptide and KB production in diabetes. These results suggest that a selective defect of beta-OHB peripheral utilization is important in determining and maintaining severe diabetic ketoacidosis.
Brown adipose and metabolic features of chronic diet-induced obesity
Authors: Levin B. E. , Finnegan M. , Triscari J. , Sullivan A. C.
Published: December 2017

Half of the 3-mo male Sprague-Dawley rats fed a high-fat (DIO) diet for 5 mo became obese and had increased carcass lipid (106%) and plasma insulin levels (61%), despite 8% less total energy intake than chow-fed controls. Their interscapular brown adipose tissue (IBAT) was 52% heavier with 45% more lipid and larger uni- and multilocular cells. Norepinephrine turnover was normal in their hearts, pancreases, and aortas but undetectable in IBAT where in vitro lipolysis, but not O2 consumption (VO2), was enhanced. Half the rats fed the DIO diet ate 17% fewer calories, gained weight equally to controls, but still had 34% more carcass lipid. Their IBAT was heavier, contained 103% more protein, with no detectable norepinephrine turnover, whereas maximal lipolysis was 73% lower and maximal VO2 was the same or even lower than controls. IBAT VO2 was stimulated by switching 8-mo chow-fed controls to the DIO diet for 7 days (which caused a 480% greater weight gain) but not by switching 8-mo obese rats to chow for 3 days. Therefore metabolic efficiency was increased while BAT VO2 and norepinephrine turnover were unchanged or reduced compared with controls by either chronic obesity or a high-fat diet.
Calcium regulation in blowflies: absence of a role for midgut
Authors: Taylor C. W.
Published: December 2017

Adult blowflies (Calliphora vicina) survive many days without increased mortality if fed 12.5 mM CaCl2 solution in place of water. Initially the calcium content of these flies rapidly increases to more than double the original content but then remains stable for many days afterward. Calcium absorption continues at a similar rate throughout this time. Midguts isolated from flies fed either 12.5 mM CaCl2 solution or distilled water have the same capacity to absorb calcium. Dopamine, octopamine, proctolin, and 5-hydroxytryptamine, at pharmacological doses, do not affect calcium absorption by the isolated midgut. Malpighian tubules are the site of most rapid calcium turnover when flies are fed excess calcium. It is concluded that excretion and not absorption is the major site of hemolymph calcium regulation in C. vicina. This contrasts to the situation in mammals where transcellular calcium absorption by the duodenum is precisely controlled. It is suggested that to avoid high luminal calcium concentrations, fast calcium absorption from the blowfly midgut is adapted to remove calcium from the lumen rather than to regulate hemolymph calcium concentration.
Diurnal changes in thermoregulatory behavior in rats with medial preoptic lesions
Authors: Szymusiak R. , DeMory A. , Kittrell E. M. , Satinoff E.
Published: December 2017

Rats with medial preoptic area (MPOA) damage lack adequate autonomic thermoregulatory reflexes but can behaviorally regulate their body temperatures (Tb) in the cold and heat. We examined the performance of such rats on 90-min behavioral thermoregulatory tests. Tests were conducted during the day and night to determine the preferred Tb at different phases of the circadian Tb rhythm. The amplitude of this rhythm was exaggerated after electrolytic MPOA lesions; differences of 3-4 degrees C between daily peaks and troughs were seen (from 37 degrees C during day to 40-41 degrees C at night) compared with control variations of only 1.5-2.0 degrees C (from 36.0-36.5 degrees C during day to 38 degrees C at night). When escaping cold during the day or night or when escaping heat at night, both MPOA-damaged and control rats maintained Tb within +/- 0.5 degrees C of initial values. When escaping heat during the day, control and MPOA-damaged rats allowed their TbS at the end of the 90-min behavioral tests to rise to normal night levels (38 degrees C for controls and 40-41 degrees C for MPOA rats). These results demonstrate that rats with MPOA damage behaviorally defend the different phases of their exaggerated Tb rhythm in a manner similar to that of controls. Therefore the exaggerated swings in Tb seen in these preparations have an active regulated component and are not simply passive results of an excessive rhythm in heat production or heat conservation.
Effect of aldosterone on potassium excretion during potassium chloride infusion in sheep
Authors: Rabinowitz L. , Sarason R. L. , Yamauchi H.
Published: December 2017

Experiments were performed on normal mature ewes to quantitate the effect of acute variations in aldosterone activity on renal K excretion. Six-hour clearance studies were performed on three sheep. Treatments were control (no infusion), infusion of KCl (140 meq in 2 h) alone or with superimposed infusions of aldosterone (20 micrograms/h), or infusion of aldosterone antagonist potassium canrenoate (100 mg/h). During KCl infusion there were simultaneous increases in plasma K, K excretion, and Na excretion. Aldosterone treatment diminished the increase in plasma K and in Na excretion but increased the rate of K excretion. Canrenoate had opposite effects. The rate of change of K excretion relative to the change in plasma K was 417 for aldosterone and 102 microeq/min per meq/l for canrenoate treatments, P less than 0.05. Before KCl infusion aldosterone decreased the rate of Na excretion and the salivary Na-to-K ratio but did not alter plasma K or K excretion. Aldosterone has a potent kaliuretic action in sheep when plasma K is elevated.
Cerebral metabolism in fetal lamb after maternal infusion of ethanol
Authors: Richardson B. S. , Patrick J. E. , Bousquet J. , Homan J. , Brien J. F.
Published: December 2017

Cerebral uptake of glucose and O2 (VCO2) was measured in 10 chronically catheterized fetal lambs during a control period, after a 1-h maternal infusion of ethanol (1.0 g X kg-1 X h-1) and 1-h postethanol infusion, to determine if alterations in cerebral metabolism might occur. Brachiocephalic artery and sagittal vein blood samples were analyzed for glucose, O2 content, blood gases, pH, and ethanol. Cerebral blood flow (Qc) was measured with a radioactive microsphere technique. VCO2 decreased significantly, from 140 +/- 13 mumol X 100 g-1 X min-1 during the control period to 91 +/- 8 (P less than 0.05) with the ethanol infusion, with a related fall in Qc, 177 +/- 12 to 104 +/- 9 ml X 100 g-1 X min-1 (P less than 0.001), the cerebral arteriovenous O2 difference being little changed. Cerebral glucose uptake, although decreased, was not significantly changed with the ethanol infusion, because the cerebral arteriovenous difference for glucose increased with the related fall in Qc. We conclude that maternal infusion of ethanol results in a decreased fetal VCO2 with a related fall in Qc. If prolonged, this decrease in cerebral oxidative metabolism might well affect cerebral development and provide a mechanism whereby chronic alcohol intake contributes to central nervous system growth anomalies and dysfunction of infants exposed to alcohol in utero.
Hypothalamic obesity after hypophysectomy or adrenalectomy: dependence on corticosterone
Authors: King B. M. , Smith R. L.
Published: December 2017

Recent studies have found that the hyperphagia and obesity resulting from lesions of the ventromedial hypothalamus (VMH) are both reversed and prevented by complete adrenalectomy. Several previous experiments, however, reported little or no suppression of VMH weight gain in hypophysectomized (HYPOX) rats. This study directly compared the effects of hypophysectomy and adrenalectomy on hypothalamic obesity in adult female rats. Complete adrenalectomy (i.e, stress-induced plasma corticosterone less than 1.0 micrograms/dl) totally suppressed abnormal weight gain in the first 20 days after VMH lesions but did not affect intracranial self-stimulation. Hypophysectomy also resulted in suppression of weight gain, but the HYPOX-VMH rats nevertheless gained significantly more weight than HYPOX rats with sham lesions. However, the HYPOX-VMH animals had very low levels of plasma corticosterone and adrenocorticotropin (ACTH) (from residual pituitary tissue or of diencephalic origin), and incompletely adrenalectomized rats with similar low levels of plasma corticosterone gained an equal amount of weight after VMH lesions. It was concluded that adrenal glucocorticoid hormones play a largely permissive role in the VMH syndrome, with only very small levels required for the manifestation of obesity.
Effect of pulmonary and renal circulations on activity of atrial natriuretic factor
Authors: Weselcouch E. O. , Humphrey W. R. , Aiken J. W.
Published: December 2017

The effect of passage through the pulmonary and renal circulation on the activity of extracted and synthetic atrial natriuretic factors was determined by monitoring the amount of the vascular relaxing activity surviving passage through the organ. When crude atrial extract was infused through isolated perfused lungs of the guinea pig, approximately 75% of its activity survived. The activity of a 23-amino acid synthetic atrial peptide was decreased 21% on passage through these lungs, but this loss of activity was not significantly different from the crude extract. Analogous experiments in vivo showed that passage through the pulmonary circulation of the dog did not alter the activity of either the crude atrial extract or of synthetic atrial peptide. In contrast to the lack of effect of the pulmonary circulation, approximately 80% of the activity of crude atrial extract and synthetic atrial peptide was removed by the isolated perfused kidney of the rabbit, and in vivo the dog kidney removed approximately 80% of the activity of both these atrial substances. By surviving transit through the pulmonary circulation, these materials exhibit a necessary property of a circulating hormone stored in the right atrium, and the fact that the renal circulation extracts most of these materials is consistent with the kidney being a target organ of this putative hormone.
Phospholipid and adenine nucleotide metabolism in muscle after burn injury
Authors: Turinsky J. , Chaudry I. H.
Published: December 2017

The role of phospholipid and adenine nucleotide metabolism in postburn unresponsiveness of muscle to insulin was examined. A single hindlimb scald in the rat was produced, and 3 days later soleus muscles were incubated in vitro with and without insulin. Under basal conditions muscles from the burned limbs had normal contents of phosphatidylcholine and phosphatidylinositol but decreased diphosphatidylglycerol (-39%) and phosphatidylethanolamine (-24%) and increased sphingomyelin (+62%), lysophosphatidylcholine (+68%), and phosphatidylserine (+13%) compared with the contralateral unburned limb. Such muscle also incorporated 107-396% more [32P]phosphate into all measured phospholipids, except for diphosphatidylglycerol. The presence of insulin had no effect on either the mass of phospholipids or 32P incorporation in any muscle. The burned limb muscles (frozen in situ) also exhibited lower levels of ATP (-25%) and total adenine nucleotides (-24%) than uninjured muscle but normal adenylate energy charge. The burned limb muscles had lower adenosine (-37%), but inosine and hypoxanthine were 82 and 39% higher, respectively. These data suggest recovery of muscle from local thermal injury is associated with alterations in mass, and possibly also turnover, of tissue phospholipids, the measured phospholipids do not mediate the postreceptor action of insulin in normal muscle, energy charge of the recovering injured muscle is restored before ATP level at the time when this muscle is unresponsive to insulin stimulation.
Mechanism of action of vasoconstrictor responses to atriopeptin II in conscious SHR
Authors: Lappe R. W. , Todt J. A. , Wendt R. L.
Published: December 2017

Previous studies have demonstrated that infusion of synthetic atriopeptin II (AP II) lowered arterial pressure, reduced regional blood flow, and increased total peripheral and regional vascular resistances in conscious spontaneously hypertensive rats (SHR). This study was designed to examine the mechanism(s) involved in regional vasoconstrictor responses to AP II. In these experiments, hemodynamic actions of AP II were examined in control, 6-hydroxydopamine-treated (chemically sympathectomized), and renal-denervated groups of instrumented conscious SHR. Infusion of AP II (1 microgram X kg-1 X min-1) caused similar reductions in mean arterial pressure in control (-22 +/- 2 mmHg), chemically sympathectomized (-23 +/- 2 mmHg), and renal-denervated (-23 +/- 3 mmHg) SHR. In control SHR, AP II infusion reduced renal (-20 +/- 3%), mesenteric (-26 +/- 2%), and hindquarters (-18 +/- 10%) blood flow and increased regional vascular resistance in all three beds. Chemical sympathectomy prevented the fall in renal blood flow (RBF) and significantly abolished the regional vasoconstrictor responses to AP II infusion. In unilateral renal-denervated groups of SHR, AP II reduced renal vascular resistance (RVR) -11 +/- 3% but failed to alter RBF (-3 +/- 1%) in denervated kidneys. In contrast, RVR increased (20 +/- 7%) and RBF was significantly reduced (-29 +/- 3%) in contralateral-innervated kidneys. This study demonstrated that chemical or surgical destruction of renal sympathetic nerves abolished AP II-induced increases in RVR. These data further indicate that in conscious SHR the regional vasoconstrictor responses to AP II infusion appear to be mediated by increases in sympathetic tone rather than through direct vascular actions of AP II.
Phosphofructokinase control in muscle: nature and reversal of pH-dependent ATP inhibition
Authors: Dobson G. P. , Yamamoto E. , Hochachka P. W.
Published: December 2017

The kinetic and regulatory properties of rabbit muscle phosphofructokinase (PFK:EC 2.7.1.11) have been reexamined in an attempt to clarify how the enzyme could achieve significant catalytic rates over the physiological pH range (down to 6.4). At 5.0 mM ATP, the apparent Km for fructose 6-phosphate (fructose 6-P) increases by at least 50-fold as the pH is decreased from 7.67 to 6.8 in 50 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-KOH buffer at 25 degrees C (7.50 to 6.63 at 37 degrees C). This effect can be nearly completely abolished in the presence of 10 microM fructose 2,6-bisphosphate (fructose 2,6-P2), with the greatest percentage change seen at low pH. In this case, the rabbit enzyme behaves as if the ATP concentration was low (1.0 mM) at any given pH. Conversely, at high ATP levels and a low pH of 6.8 at 25 degrees C, PFK behaves in the presence of fructose 2,6-P2 as if the pH has been increased to approximately 7.15 or a 0.35 pH unit shift at any given fructose 6-P concentration. At physiological concentration of fructose 6-P (0.1 mM), the positive effectors glucose 1,6-bisphosphate (glucose 1,6-P2) and either AMP, inorganic phosphate, or NH4+ were found to be, respectively, 60 and 40% as effective as fructose 2,6-P2 in reversing this pH-dependent ATP inhibition over the physiological pH range. In combination, however, glucose 1,6-P2 plus AMP were as effective as fructose 2,6-P2.(ABSTRACT TRUNCATED AT 250 WORDS)
Propylthiouracil causes phase delays and circadian period lengthening in male and female hamsters
Authors: Morin L. P. , Gavin M. L. , Ottenweller J. E.
Published: December 2017

The thyroid neuroendocrine axis has been implicated in the control of circadian rhythmicity. The present work examined the ability of a thyroid hormone-inhibiting agent, propylthiouracil (PTU), to modulate phase and period of the hamster wheel-running circadian rhythm. The circadian period (tau) of blind male hamsters was lengthened by approximately 0.2 h when they were fed a diet containing 0.6% PTU. Removal of the PTU reversed the change in tau. Pinealectomy did not alter the tau response to PTU. Blind ovariectomized female hamsters showed changes in tau during and after PTU treatment that were similar to those of males. Males were also tested with 0.3, 0.6, or 1.2% PTU diets, and a dose-response relationship was established. Under 14:10 light-dark (LD 14:10) conditions, the phase of activity onset relative to lights off (psi) was not affected by 0.6% PTU. In LD 6:18, mean psi was 16.7 h, but this shortened to 13.3 h during PTU, returning to 16.0 h after PTU removal. In intact males under LD 14:10, the three PTU diet concentrations failed to differentially suppress thyroxine and triiodothyronine levels. Food intake and body weight were differentially reduced by the PTU treatments. A 0.5% quinine hydrochloride diet also reduced food intake and body weight but did not change tau. The inconsistency between the dose-tau response and the dose-thyroid hormone response suggest that PTU may affect circadian rhythmicity independent of its action on the thyroid neuroendocrine axis.
Angiotensin II attenuates baroreflexes at nucleus tractus solitarius of rats
Authors: Casto R. , Phillips M. I.
Published: December 2017

Microinjection of angiotensin II (ANG II) into the nucleus tractus solitarius (NTS) has been shown to produce a dose-dependent increase in blood pressure and heart rate. We have tested the effect of subpressor infusions of ANG II (10 ng . kg-1 . min-1) in the NTS on reflex bradycardia after intravenous administration of the vasoconstrictor phenylephrine (1-12 micrograms) in normotensive urethan-anesthetized rats. ANG II within the brain is thought to contribute to the decreased baroreflex sensitivity in spontaneously hypertensive rats (SHR). The sensitivity of the baroreflex was significantly decreased by the infusion of ANG II (1.01 +/- 0.08) compared with control (2.41 +/- 0.51) in the normotensive animals. Baroreflex sensitivity was significantly decreased in SHR (0.40 +/- 0.21) compared with normotensive animals. We conclude that ANG II within the NTS can inhibit the function of baroreceptor reflexes in normotensive animals, suggesting that the endogenous peptide may perform an inhibitory role in the baroreflex arc, and this is further evidence that central ANG II is involved in blood pressure of SHR.
Effects of ovarian hormones on energy balance and brown adipose tissue thermogenesis
Authors: Richard D.
Published: December 2017

This study was carried out to investigate the nutritional energetics of ovariectomized rats with or without ovarian hormone replacement. Rats were divided into five groups: 1) sham operated, 2) ovariectomized, 3) ovariectomized and treated with progesterone, 4) ovariectomized and treated with estradiol, or 5) ovariectomized and treated with estradiol and progesterone. After 36 days of treatment, energy contents of all five groups were determined together with energy content of food and feces. Brown adipose tissue thermogenesis was assessed through mitochondrial GDP binding assay. Results show that ovariectomy leads to a 16% increase in metabolizable energy intake. This increase was accompanied by a twofold increase in body energy gain. Progesterone did not further affect energy intake and gain in ovariectomized rats. However, increases in both food intake and energy gain were prevented by the estradiol replacement therapy. There was no difference in energy expenditure between sham-operated and ovariectomized rats in the absence of estradiol. In estradiol-treated animals, energy expenditure (kJ.kg body wt-0.75 . day-1) showed a slight increase. There was no difference in protein content of interscapular brown adipose tissue between all five groups. GDP binding was slightly reduced in ovariectomized estradiol-treated rats. It is concluded from this study that ovarian hormones produce their effects on energy balance mainly by altering food intake.
Food restriction and reproductive development: male and female mice and male rats
Authors: Hamilton G. D. , Bronson F. H.
Published: December 2017

The effect of food restriction on reproductive development was compared in male and female mice. This was accomplished using an experimental design that allowed us to assess the amount of reproductive development that could occur in the total absence of body growth, when growth was stopped at each of three different body weights. Our results demonstrate that reproductive development has much more inertia in males than in females. Specifically, the final stages of reproductive development can proceed largely independently of body growth in males but not in females. This same design was also employed in an abbreviated study of male rats. When its results are coupled with the existing literature for female rats, it appears as though the sex differences noted above are characteristic of both species.
Body temperature and rate of O2 consumption in Chinese pangolins
Authors: Heath M. E. , Hammel H. T.
Published: December 2017

Body temperatures and rates of O2 consumption and CO2 production were measured in four Chinese pangolins (Manis pentadactyla) during short-term exposures (2-4 h) to ambient temperatures (Ta) of 10-34 degrees C. At Ta less than 27 degrees C the pangolins curled into a sphere. At Ta greater than 28 degrees C the animals laid on their backs with their soft abdominal skin exposed. Rectal temperatures between 33.4 and 35.5 degrees C were recorded from animals exposed to Ta of 10-32 degrees C. At Ta greater than or equal to 32 degrees C the animals appeared to be markedly heat stressed, rate of breathing was elevated, and core temperature rose somewhat. Resting metabolic rates averaged 3.06 ml O2 X kg-1 X min-1. This is significantly lower than would be predicted from the relationship between body mass and metabolic rate established by Kleiber (The Fire of Life: an Introduction to Animal Energetics. New York: Wiley, 1975) for other eutherian mammals. The magnitude of the metabolic response to Ta below the lower critical temperature was inversely correlated to the mass of the pangolin, the slope being greatest for the smallest animals. Respiratory quotients of 0.85-1.0 were observed.
Regional circulatory responses to hypocapnia and hypercapnia in bar-headed geese
Authors: Faraci F. M. , Fedde M. R.
Published: December 2017

To investigate mechanisms that may allow birds to tolerate extreme high altitude (hypocapnic hypoxia), we examined the effects of severe hypocapnia and moderate hypercapnia on regional blood flow in bar-headed geese (Anser indicus), a species that flies at altitudes up to 9,000 m. Cerebral, coronary, and pectoral muscle blood flows were measured using radioactive microspheres, while arterial CO2 tension (PaCO2) was varied from 7 to 62 Torr in awake normoxic birds. Arterial blood pressure was not affected by hypocapnia but increased slightly during hypercapnia. Heart rate did not change during alterations in PaCO2. Severe hypocapnia did not significantly alter cerebral, coronary, or pectoral muscle blood flow. Hypercapnia markedly increased cerebral and coronary blood flow, but pectoral muscle blood flow was unaffected. The lack of a blood flow reduction during severe hypocapnia may represent an important adaptation in these birds, enabling them to increase O2 delivery to the heart and brain at extreme altitude despite the presence of a very low PaCO2.
Effect of amine on temperature-responsive neuron in slice preparation of rat brain stem
Authors: Watanabe T. , Morimoto A. , Murakami N.
Published: December 2017

Using slice preparations we investigated the effect of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) on thermoresponsive neurons in the hypothalamus, midbrain, and the medulla oblongata. NE inhibits the activities of most of the warm-responsive neurons (11 out of 13 neurons) but 5-HT activates the warm-responsive neurons (10 out of 11 neurons) in the hypothalamus. However, the direction of neuronal response of the midbrain was opposite of that in the hypothalamus when 5-HT was applied. In the medulla oblongata, 5-HT facilitates both warm- and cold-responsive neurons and NE facilitates or inhibits these neurons in equal proportions. Furthermore, the dose-response relationships were determined using slice preparations. In the hypothalamus and the midbrain, NE and 5-HT started to effect the warm-responsive neurons at the minimum concentration of 5 X 10(-6) M, whereas the maximum responses were obtained at the concentration of 5 X 10(-5) M. In the medulla oblongata, NE or 5-HT changed the activities of the warm-responsive neurons in the range of 5 X 10(-5) to 10(-3) M or 10(-6) to 10(-5) M, respectively. It is concluded that the thermoresponsive neurons respond to 5-HT and NE in different ways, at both various levels in the central nervous system and the applied concentration of amines.
Suppression of renin release by antagonism of endogenous opiates in the dog
Authors: Szilagyi J. E. , Chelly J. , Doursout M. F.
Published: December 2017

The influence of blockade of endogenous opioids on the release of renin due to partial renal arterial constriction was determined acutely and chronically in unilaterally nephrectomized dogs. In acute preparations changes in plasma renin activity, arterial blood pressure, and heart rate were determined after 15 min of 60% renal arterial constriction before and after administration of either a saline vehicle, the opiate antagonist naloxone (0.05 mg/kg), or morphine (2 mg/kg). Acute antagonism of endogenous opiates abolished the increase in plasma renin activity and mean arterial pressure associated with renal arterial constriction. Repeated renal arterial constrictions in saline- or morphine-treated animals did not alter the humoral or hemodynamic responses. In chronic preparations long-term naloxone infusion attenuated the development of renovascular hypertension and diminished the increase in plasma renin activity. These data suggest that endogenous opioid peptides are modulators in the control of renin release and may be important participants in the pathogenesis of hypertension.
Physiology of the circadian timing system: predictive versus reactive homeostasis
Authors: Moore-Ede M. C.
Published: December 2017

Since Cannon first formulated the concept of homeostasis 60 years ago, attention has been focused on the corrective responses initiated after the steady state of the organism is perturbed. In this lecture it is argued that the concept of homeostasis should be extended to include the precisely timed mechanisms of the circadian (and circannual) timing system which enables organisms to predict when environmental challenges are most likely to occur. A mature understanding of homeostasis should encompass both "reactive" responses to changes in physiological variables which have already occurred and the "predictive" responses initiated in anticipation of predictably timed challenges. Such predictive responses have particular value because they enable physiological mechanisms to be utilized immediately, even if they involve a delay of several hours, by activating them at a suitable time in advance of a probable challenge. However, conflicts may often occur between predictions and reality. Examples from sleep-wake behavior, thermoregulation, blood volume homeostasis, and the regulation of potassium balance show that predictive responses often compromise the effectiveness of reactive homeostatic mechanisms even to the point of risking the survival of the organism. It must be concluded that the day-night cycle of the natural environment has played a fundamental role in shaping the evolutionary development of homeostatic mechanisms because of the dominating predictability of diurnal changes in illumination, temperature, food availability, and predator activity.
Cardiac and splenic norepinephrine turnover during septic peritonitis
Authors: Jones S. B. , Kovarik M. F. , Romano F. D.
Published: December 2017

Postganglionic sympathetic activity was assessed in heart and spleen tissue in conscious rats under conditions of developing septic shock by quantitating norepinephrine (NE) turnover. Fasted male rats were subjected to cecal ligation and puncture and allowed to recover for 12-14 h. NE turnovers were measured by following the rate of [3H]NE decay, and measurements were made between 12 and 24 h after surgery. Plasma glucose and lactate were determined at times throughout the turnover protocol. NE turnover in cardiac tissue of septic animals was increased (0.134 micrograms X g-1 X h-1) in comparison with both surgical sham (0.052 micrograms X g-1 X h-1) and unoperated controls (0.051 micrograms X g-1 X h-1). NE turnover rates were also elevated in spleen tissue of septic rats (0.152 micrograms X g-1 X h-1) in comparison with both surgical sham (0.094 micrograms X g-1 X h-1) and unoperated controls (0.087 micrograms X g-1 X h-1). Plasma glucose levels suggest that septic rats are in the hyperglycemic phase of sepsis. These experiments support the concept of increased peripheral sympathetic outflow during the development of septic shock that would support hypermetabolic and subsequent hyperdynamic alterations which are well-recognized characteristics of the early stages of sepsis leading to septic shock.
Neurons of C1 area mediate cardiovascular responses initiated from ventral medullary surface
Authors: Benarroch E. E. , Granata A. R. , Ruggiero D. A. , Park D. H. , Reis D. J.
Published: December 2017

We sought to establish whether neurons of the C1 area of the rostral ventrolateral medulla (RVL) mediate changes in arterial pressure and heart rate evoked by topical application of drugs to the ventral medullary surface of the rat. Animals were anesthetized, paralyzed, and ventilated. The ventral surface was mapped with L-glutamate, and a restricted zone was identified from which L-glutamate, as well as kainic acid, bicuculline, strychnine, carbachol, or physostigmine, increased arterial pressure and heart rate. The hypertensive effects of carbachol and physostigmine were blocked by previous local application of atropine but not hexamethonium. Application of gamma-aminobutyric acid (GABA) or glycine to this area produced hypotension and bradycardia. Located caudal to the trapezoid bodies and lateral to the pyramids, this area corresponded to points with lowest threshold for pressor responses evoked by electrical stimulation and overlapped the distribution of epinephrine-synthesizing cells of the RVL. Processes arising from these neurons were identified reaching and contacting the ventral surface. Unilateral lesions involving the C1 area or phenylethanolamine-N-methyltransferase-labeled descending axons derived from this area imparied by greater than 70% the response to ipsilateral application of L-glutamate, GABA, or glycine to the ventral surface. We suggest that neurons within the C1 area of RVL adjacent to or including epinephrine cells may mediate cardiovascular changes elicited from a restricted chemosensitive zone of the ventral medullary surface of the rat.
Angiotensin-stimulated drinking in marine fish
Authors: Beasley D. , Shier D. N. , Malvin R. L. , Smith G.
Published: December 2017

Drinking rates in both marine and freshwater stenohaline fish were studied by measuring the ingestion of polyethylene glycol that had been added to the aquarium water. Two marine species, the long-horned sculpin and the flounder, and three freshwater species, the common goldfish, the mottled sculpin, and the common shiner, were used. Control drinking rates in freshwater fish averaged 0.03-0.1% body wt/h and in marine fish varied between 0.06 and 0.24% body wt/h. Intramuscular injections of angiotensin II (ANG II) stimulated drinking two- to threefold in the two marine species but had no effect on the drinking rate of the freshwater species. Hemorrhage (1-2% of body wt) also stimulated drinking in the two marine species (6- to 10-fold) but did not affect the drinking rate of two freshwater species. Thus exogenous ANG II and hemorrhage stimulate drinking in two marine stenohaline fish as they do in mammals. These responses were absent in the three freshwater fishes studied. However, injection of converting enzyme inhibitor (SQ 20881) or saralasin in order to block endogenous ANG II did not attenuate either basal or hemorrhage-stimulated drinking in the marine fish.
Effects of aging on prostate growth in beagles
Authors: Berry S. J. , Coffey D. S. , Ewing L. L.
Published: December 2017

Statistical analysis of 82 variables was completed to determine the effects of aging in the male beagle on prostatic growth and function. The results indicate that prostate weight increased to 4 yr and then reached a plateau. Prostatic secretory function (measured as ejaculate volume) followed a course different than the growth of the gland. Prostatic function increased and reached a peak at 4 yr and then declined abruptly. Therefore, there is a separation of the growth and secretory function of the canine prostate after 4 yr of age. Multiple linear regression analysis was performed to determine the mathematical relationship of these variables in predicting prostate weight and therefore benign prostatic hyperplasia, which is correlated with weight. The testicular secretion of testosterone and aging were paramount factors in predicting prostate weight. There appears to be an increased sensitivity of the prostate to testosterone secretion with advancing age.
Nucleus paragigantocellularis lateralis and lumbar sympathetic discharge in the rat
Authors: Guyenet P. G. , Brown D. L.
Published: December 2017

Two classes of medullospinal units with inhibitory baroreceptor inputs [nucleus paragigantocellularis lateralis (PGCL) units] were recorded in PGCL (conduction velocity 3.1 and 0.67 m/s, respectively). Single-pulse stimulation of PGCL produced two peaks of activation of the lumbar sympathetic chain [sympathetic nerve discharge (SND)] with latencies of 98 and 206 ms. After substracting the delay due to impulse propagation between cord and sympathetic chain (64 ms), a conduction velocity of 2.8 and 0.67 m/s could be estimated for the medullospinal portion of the two sympathoexcitatory pathways stimulated in the PGCL. R wave-triggered activity histograms of PGCL unit discharge and lumbar SND exhibited a similar pattern with one major trough, occurring 108 ms later at the level of the sympathetic chain. It is concluded that PGCL contains two classes of medullospinal neurons with sympathoexcitatory function, the fast-conducting type being predominantly responsible for the cardiac-related rhythm of lumbar SND. Finally, averaging techniques revealed a large respiratory rhythm of lumbar SND in spontaneously breathing rats, but little or no such rhythm could be detected at the level of most PGCL sympathoexcitatory cells.
Temporal evolution of altered islet neurotransmitter sensitivity after VMH lesion
Authors: Campfield L. A. , Smith F. J. , Larue-Achagiotis C.
Published: December 2017

It has been suggested that increased insulin secretion after ventromedial hypothalamic (VMH) obesity is mediated by decreased sympathetic and increased parasympathetic neural input. The evolution of pancreatic islet adaptation was studied from 1 to 130 days after VMH lesion in rats by assessing the sensitivity of insulin secretion from incubated isolated islets to 10 mM glucose and selected acetylcholine and norepinephrine concentrations. Insulin secretion in response to glucose increased by 1 day, reaching a twofold plateau from 7 to 130 days. Sensitivity to norepinephrine increased by 1 day, whereas sensitivity to acetylcholine decreased by 2 days, and both remained altered up to 130 days. These data suggest that elevated plasma insulin concentrations characteristic of VMH obesity were associated with increased insulin secretion in response to glucose before decreased sensitivity to acetylcholine and concurrent with increased sensitivity to norepinephrine. We conclude that these compensatory responses, which shift the islet to a new operating point secondary to altered neural input, are essential to pancreatic adaptation in VMH obesity.
Protons, osmolytes, and fitness of internal milieu for protein function
Authors: Somero G. N.
Published: December 2017

The composition of the intracellular milieu shows striking similarities among widely different species. Only certain values of intracellular pH, values that generally reflect alphastat regulation, and only narrow ranges of inorganic ion concentrations are found in the cytoplasm of the cells of most animals, plants, and microorganisms. In water-stressed organisms only a few types of low-molecular-weight organic molecules (osmolytes) are accumulated. These highly conserved characteristics of the intracellular fluids reflect the need to maintain critical features of macromolecules within narrow ranges optimal for life. For proteins these features include maintaining adequate rates of catalysis, a high level of regulatory responsiveness, and a precise balance between stability and lability of structure (tertiary conformation, subunit assembly, and multiprotein complexes). The optimal values for these functional and structural features of proteins often lie near the midrange of possible values for these properties, and only under specific conditions of intracellular pH, ionic strength, and osmolyte composition are these optimal midrange values conserved. In dormant cells the departure of solution conditions from values that are optimal for protein function and structure may be instrumental in reducing or shutting down metabolic functions. Seen from a broad evolutionary perspective, the evolution of the intracellular milieu is an important complement to macromolecular evolution. In certain instances appropriate modifications of the internal milieu may reduce the need for adaptive amino acid replacements in proteins.
Sympathetic control of adrenal secretion of enkephalins after hemorrhage in awake dogs
Authors: Engeland W. C. , Bereiter D. F. , Gann D. S.
Published: December 2017

Adrenomedullary secretion of methionine (Met)-enkephalin and of leucine (Leu)-enkephalin was measured in awake trained dogs subjected to 10 or 20% hemorrhage. Enkephalin secretory rates increased in proportion to the magnitude of hemorrhage with the ratio of Met-enkephalin to Leu-enkephalin being approximately 4:1. Arterial concentrations of enkephalins reflected adrenal secretion only in dogs exhibiting the largest secretory responses to hemorrhage. Cross-correlation analysis of 12 individual experiments showed that Met-enkephalin and epinephrine secretory rates were maximally correlated at 0-min delay, suggesting that enkephalins are cosecreted with catecholamines. The molar ratio in adrenal venous blood of epinephrine to Met-enkephalin ranges from 480 +/- 50 to 570 +/- 60. Chronic denervation of the adrenal by removing thoracic and lumbar splanchnic nerves prevented the Met-enkephalin and catecholamine secretory responses to hemorrhage. These data show that the adrenal medulla secretes enkephalins in response to stimuli activated by hemorrhage. These findings suggest that secretion of opiate-like peptides into the peripheral circulation may be a component of the sympathetic response to trauma.
Kinetic analysis of zinc metabolism and its regulation in normal humans
Authors: Wastney M. E. , Aamodt R. L. , Rumble W. F. , Henkin R. I.
Published: December 2017

Zinc metabolism was studied in 32 normal volunteers after oral (n = 25) or intravenous (n = 7) administration of 65Zn. Data were collected from the blood, urine, feces, whole body, and over the liver and thigh regions for 9 mo while the subjects consumed their regular diets (containing 10 mg Zn ion/day) and for an additional 9 mo while the subjects received an exogenous oral supplement of 100 mg Zn ion/day. Data from each subject were fitted by a compartmental model for zinc metabolism that was developed previously for patients with taste and smell dysfunction. These data from normal subjects were used to determine the absorption, distribution, and excretion of zinc and the mass of zinc in erythrocytes, liver, thigh, and whole body. By use of additional data obtained from the present study, the model was refined further such that a large compartment, which was previously determined to contain 90% of the body zinc, was subdivided into two compartments to represent zinc in muscle and bone. When oral zinc intake was increased 11-fold three new sites of regulation of zinc metabolism were identified in addition to the two sites previously defined in patients with taste and smell dysfunction (absorption of zinc from gut and excretion of zinc in urine). The three new sites are exchange of zinc with erythrocytes, release of zinc by muscle, and secretion of zinc into gut. Regulation at these five sites appears to maintain some tissue concentrations of zinc when dietary zinc increases.
Relating left ventricular dimension to maximum elastance by fiber mechanics
Authors: Beyar R. , Sideman S.
Published: December 2017

The dependence of the pressure-volume slope, which defines the maximum elastance (Emax) and the zero pressure-volume intercept (Vd) on the size and dimensions of the left ventricle (LV), is theoretically studied, and a normalizing parameter for Emax is suggested for normal and hypertrophied hearts. The study is based on our earlier model of the mechanics of the LV contraction, which assumes a nested-shell spheroidal shape, Streeter's fiber angle distribution, given stress-length and stress-strain rate functions of the sarcomeres, a radial propagation of the electrical activation front, and a windkessel arterial model. The study shows that Emax is linearly related to the maximum force that the optimal length sarcomeres can develop (sigma o), which is a characteristic measure of the contractility. Emax decreases and Vd increases with an increase in ventricular size, at a constant end-diastolic ratio (h/b)ed, where h is the wall thickness, and b is the semiminor axis of the prolate spheroidal LV. When the reference unstressed volume (V0) is held constant and the wall thickness increases, as in pure concentric hypertrophy, Emax decreases slightly and shifts to the left to a lower Vd value. In pure eccentric hypertrophy, wherein chamber size increases while the wall thickness remains constant, Emax decreases and Vd increases. A good index for myocardial function at constant configuration ratio (h/b)ed is obtained by multiplying Emax with the LV muscle volume (Vm). (h/b)ed is constant (= 0.45) for the normal heart but increases for concentric hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Clearance and tissue distribution of fibronectin in septic rats: relationship to synthetic rate
Authors: Kiener J. L. , Saba T. M. , Cho E. , Blumenstock F. A.
Published: December 2017

Fibronectin is a glycoprotein found in a soluble form in plasma and in an insoluble form in many tissues. We evaluated the influence of postoperative intraperitoneal sepsis on the clearance, tissue distribution, and synthesis of plasma fibronectin in rats (300-400 g). Experimental sepsis was induced by cecal ligation following laparotomy, whereas control animals underwent laparotomy (5 cm) alone. At 24 and 48 h after laparotomy, plasma fibronectin levels were normal. After laparotomy plus cecal ligation, plasma fibronectin increased by 47% at 24 h and remained elevated (52% above 0 time) at 48 h. At 24 h postsurgery the disappearance and tissue distribution of 75Se-plasma fibronectin and 75Se-plasma albumin was evaluated. Tissue distribution was quantified at 2 and 24 h after intravenous injection of both tracer proteins in separate groups. Both fibronectin and albumin demonstrated an initial distribution between vascular and extravascular sites and then a progressive decrease in plasma. In control (laparotomy) rats the half-life (t1/2) for plasma clearance of 75Se-plasma fibronectin was 25.33 +/- 2.53 h compared with 13.21 +/- 0.78 h in the septic rats. Septic rats manifested decreased sequestration of 75Se-fibronectin at the area of surgical incision (laparotomy), increased sequestration at the focus of intraperitoneal infection, and increased uptake in the nonviable portion of the cecum. The synthetic rate for plasma fibronectin in laparotomized control rats was 3.03 +/- 0.29 mg X 100 g-1 X 24 h-1, whereas after laparotomy plus cecal ligation the synthetic rate increased to 4.58 +/- 0.35 mg X 100 g-1 X 24 h-1. In contrast the synthetic rate for albumin decreased from 84.70 +/- 1.66 mg X 100 g-1 X 24 h-1 in controls to 52.38 +/- 1.77 mg X 100 g-1 X 24 h-1 in the septic animals. Thus intraperitoneal sepsis in the rat will enhance the vascular clearance, alter the distribution, and increase the synthetic rate for plasma fibronectin.