bluuebunny/crossref_metadata_2025 huggingface dataset:
Sympathetic nerve function and vascular reactivity in Doca-salt hypertensive rats
Authors: Ekas R. D. , Lokhandwala M. F.
Published: December 2017

The present study was conducted to measure norepinephrine release during sympathetic nerve stimulation and to evaluate vascular reactivity in the isolated perfused mesenteric vasculature of normotensive and Doca-salt hypertensive rats. Significantly greater vasoconstrictor responses to periarterial nerve stimulation, norepinephrine, and vasopressin, but not to barium chloride, were observed in the mesenteric vasculature of the hypertensive rats in comparison with the control normotensive group. Norepinephrine release, measured as total tritium overflow, during periarterial nerve stimulation at 4 Hz for 2 min, was identical in both normotensive and hypertensive animals. Phentolamine (5.3 micro M) significantly increased tritium overflow, but to the same extent in the normotensive and the hypertensive mesenteric vasculature, suggesting that the negative feedback presynaptic alpha-adrenoceptor mechanism, which has been proposed to modulate transmitter release, was unaltered in this form of hypertension. These results indicate that hyperresponsiveness of the mesenteric vasculature to periarterial nerve stimulation in the hypertensive rats is due to increased sensitivity of the vascular alpha-adrenoceptor and not facilitation of the transmitter release. The increased vascular reactivity to norepinephrine and vasopressin may be involved in the maintenance of Doca-salt hypertension.
Optoelectronic transducer for in vivo recording of oviductal contractile activity
Authors: Halbert S. A. , Bourdage R. J. , Boling J. L. , Ringo J. A. , Blandau R. J.
Published: December 2017

An optoelectronic instrument to record oviductal muscular activity in chronically instrumented animals was evaluated in in vitro and in vivo experiments. The intensity of red light transmitted through the oviduct was modulated by contractions of the oviductal wall producing an optical analog of the mechanical events. Accuracy of the analog was tested by Fourier analysis of signals from mechanical and optoelectronic transducers placed at the same site on the oviduct; the results validated the use of the optical device as a contraction event sensor. Contractions of the tubal mesenteries had less effect on the optical signal than on signals from extraluminal mechanical transducers. Optical and photographic recordings of luminal transport in exposed oviducts showed a correspondence of intraluminal movements to events in the optical contraction signal. This instrument does not alter tubal function, and thus it is an especially useful experimental tool to investigate the role of oviductal muscular activity in fertility.
Glucose homeostasis in a carnivorous animal (cat) and in rats fed a high-protein diet
Authors: Kettelhut I. C. , Foss M. C. , Migliorini R. H.
Published: December 2017

Glucose homeostasis in a carnivorous (cat) and in an omnivorous (rat) animal fed a high-protein, low-carbohydrate (HP) diet followed a pattern similar to that previously found in carnivorous birds [Am. J. Physiol. 234 (Regulatory Integrative Comp. Physiol. 3): R115-R121, 1978]. Thus, compared to controls given carbohydrate-rich (HC) diets. HP-fed animals had, in the fed state, lower levels of blood sugar, lower concentrations of liver glycogen, and a tendency to reduced body glucose mass. During fasting, their liver glycogen was little mobilized and their glycemia remained remarkably constant. Accordingly, their body glucose mass remained unchanged. Gluconeogenic capacity, already high in the fed state, was not further activated by fasting. Phosphoenolpyruvate carboxykinase activity actually decreased in rat liver cytosol, remaining unchanged in cat liver cytosol and mitochondria. [3H]glucose turnover studies revealed that in HP-fed cats and rats glucose replacement rates in the fed state were as high as in HC-fed animals and that the resistance of their glycemia to fasting depended on the high gluconeogenic capacity and not on a more efficient reduction of glucose utilization.
Physiological and pharmacologic effects on TH activity in rabbit and cat carotid body
Authors: Gonzalez C. , Kwok Y. , Gibb J. , Fidone S.
Published: December 2017

The carotid bodies, along with the superior cervical ganglia and the adrenal glands, were removed from rabbits and cats and the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, was assayed by the method of Nagatsu (Anal. Biochem. 9: 122-126, 1964). The activities of the enzyme, in nmols tyrosine hydroxylated x h-1 x mg tissue-1, were: carotid body, rabbit 1.29, cat 0.84; superior cervical ganglion, rabbit 8.66, cat 4.97; adrenal gland, rabbit 0.95, cat 2.25. With respect to the carotid body, each of the following experimental procedures resulted in a long-term increase in TH activity in the rabbit but not in the cat: 1) severe hypoxia (5% O2 in N2 for 1 h, assay of TH 48 h later); 2) chronic transection of the carotid sinus nerve (assay of TH at 12-15 days); or 3) administration of reserpine (10 mg/kg at 0 and 24 h, assay of TH at 48 h). These observations are compared with our previous findings for rat carotid body and are discussed in relation to the role of catecholamines in chemoreception, and, in particular, to the reported differences in dopamine action in the carotid bodies of these different species. Our results also suggest species differences with respect to the participation of the sympathoadrenal system in response to reserpine and hypoxic stress.
Modeling and identification of metabolic systems
Authors: Carson E. R. , Cobelli C. , Finkelstein L.
Published: December 2017

Introductory principles of physiological systems analysis by computer simulation or computation are introduced. The problems of model formulation, identification, and validation are examined. Selected guidelines for successful modeling are suggested, and examples of such applications in the field of endocrinology and metabolism are given.
Cerebral carbohydrate and energy metabolism during hypoglycemia in newborn dogs
Authors: Vannucci R. C. , Nardis E. E. , Vannucci S. J. , Campbell P. A.
Published: December 2017

The metabolic responses of the perinatal brain to hypoglycemia were studied in newborn dogs. Hypoglycemia, induced by the intravenous injection of regular insulin (0.2-0.3 U/g body wt), resulted in final blood glucose concentrations ranging from 0.1 to 1.5 mmol/l; blood lactate levels were little changed from normoglycemic values. Righting, sucking, and nociceptive withdrawal reflexes were progressively lost during the course of hypoglycemia. Slowing of the electroencephalogram was apparent at or below 1.5 mmol/l blood glucose and advanced to paroxysmal discharges and convulsive activity as glucose approached 0.5 mmol/l. In lightly anesthetized, paralyzed, and artificially ventilated puppies, blood glucose concentrations approximating 1.0 mmol/l were associated with a 91% reduction in cerebral glucose; the concentrations of other glycolytic intermediates (glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-diphosphate, pyruvate, lactate) were unchanged from control. Further declines in blood glucose resulted in cerebral glucose levels below 0.1 mmol/kg as well as in partial depletions of all measured glycolytic intermediates including lactate. These changes reflect reduced cerebral glucose consumption and glycolytic flux. Despite the alterations in carbohydrate metabolism, both lactate/pyruvate ratios and high-energy phosphate reserves (phosphocreatine, ATP, ADP) in brain were well preserved even at the extreme of hypoglycemia. The present data, coupled with previous findings of enhanced lactic acid entry into and consumption by newborn dog brain, suggest that this metabolite serves as an important, if not the predominant, substitute fuel for cerebral oxidative metabolism during perinatal hypoglycemia.
Plasma iron, copper, and zinc in lizard Dipsosaurus dorsalis: effects of bacteria injection
Authors: Hacker M. R. , Rothenburg B. A. , Kluger M. J.
Published: December 2017

The effects of inoculation of desert iguanas (Dipsosaurus dorsalis) with heat-killed Aeromonas hydrophila on the plasma concentrations of iron, copper, and zinc, and the total iron-binding capacity have been determined. Plasma iron concentration and total iron-binding capacity fell significantly in inoculated lizards maintained at temperatures corresponding to those selected during fever. Plasma copper concentration did not change in response to inoculation (as determined at 24 h postinjection). Plasma zinc concentration fell in inoculated lizards regardless of whether the lizards were maintained at temperatures corresponding to those selected by afebrile or febrile lizards. There were no effects of varying the zinc concentration (corresponding to those observed in noninfected lizards, infected lizards, or at subnormal levels) on the in vitro growth rate of A. hydrophila. We hypothesize that the reduction in plasma zinc observed in infected mammals, and now in infected lizards, may have an effect (perhaps by some indirect pathway) on the in vivo growth rate of A. hydrophila.
Thoracic duct lymph flow and protein flux dynamics: responses to intravascular saline
Authors: Brace R. A. , Power G. G.
Published: December 2017

Fluid and protein flux responses in the left thoracic duct and vasculature were measured in pentobarbital-anesthetized, nephrectomized, adult dogs before and after four successive intravascular saline infusions of 2% of body weight each. We found three main characteristics of the thoracic lymph flow and protein flux responses to the intravenous saline: 1) lymph flow reached a peak and then decreased by approximately 40% after each infusion; 2) the maximum lymph flow occurred 5-7 min after terminating each infusion; and 3) the lymph-to-plasma protein concentration ratio fell more than may be expected from the distribution of the infused saline. We were unable to explain these experimental data with a simple two-compartment mathematical model representing the vascular and interstitial spaces. To adequately explain the data, the model had to be expanded to four compartments representing a vascular compartment, two interstitial compartments each with different capillary protein permeabilities, and a lymphatic compartment. We also found it necessary to include interstitial stress relaxation, a nonlinear function curve for lymph flow versus interstitial fluid pressure, and a complaint lymphatic system.
Behavioral responses to pyrogen in cold-stressed and starved newborn rabbits
Authors: Kleitman N. , Satinoff E.
Published: December 2017

Starvation for 2 days and a chronic mild cold stress prevented the rises in body temperature that normally occur in newborn rabbits that have been injected with pyrogen (Piromen, 5 mg/kg). Nevertheless, the stressed pups selected significantly warmer positions in a thermal gradient than did saline-injected littermates and thereby raised their body temperatures. Enhanced heat seeking and subsequent fever were also observed in normally fed pups that were incubated at 24 degrees C and had become hypothermic after pyrogen injection. The responses of the pups before they were allowed to thermoregulate behaviorally resemble the types of thermal responses to infection seen in human newborns. The temperature selection of these pups, and others, indicates that pyrogen elevates the set points of newborn rabbits when endothermic fever is attenuated or even absent.
Nonshivering thermogenesis in skeletal muscle of seasonally acclimatized mice, Peromyscus
Authors: Wickler S. J.
Published: December 2017

Nonshivering thermogenesis (NST) is a major contributor to total heat production capabilities of Peromyscus and the magnitude of the NST response increases dramatically in winter-acclimatized animals. To directly assess the contribution from skeletal muscle to this NST, a hindlimb perfusion system was developed for Peromyscus. Oxygen consumption was then measured with and without norepinephrine (the mediator of NST) in freshly captured animals in summer and winter. Norepinephrine (NE) was infused at 0.001, 0.01, and 0.1 micrograms . g hindlimb muscle-1 . min-1. Vascular resistance (VR), calculated as arterial pressure divided by flow rate, increased during all NE infusions. At doses of 0.001 and 0.01, VR stabilized after approximately 10 min, but at 0.1 VR continued to rise. Resting oxygen consumption was 0.817 +/- 0.037 and 0.805 +/- 0.049 mumol O2 . g-1 . min-1 in summer (n = 8) and winter (n = 7) animals, respectively. There was no apparent increase in oxygen consumption with any dosage of NE. It appears that the increase in NST in winter animals is not due to an increased NST in skeletal muscle.
Capillary supply of skeletal muscles from acclimatized white-footed mice Peromyscus
Authors: Wickler S. J.
Published: December 2017

Winter-acclimatized white-footed mice (Peromyscus leucopus) can increase their aerobic heat production under cold stress by 70%. The possibility that changes in microvascular supply might account, in part, for some of this increased thermogenic capacity was examined in one of the primary thermogenic tissues, skeletal muscle. Capillaries were stained histochemically in four hindlimb muscles of freshly captured Peromyscus in summer and winter. Capillary density, mean fiber area, and mean capillaries in contact per muscle fiber were obtained from the soleus, plantaris, gastrocnemius, and semitendinosus. If results from all individual muscles are combined, mean fiber area is significantly smaller (8%) and mean capillary density is significantly greater (40%) in winter muscles. The mean number of capillaries in contact is not different, but the mean ratio of capillaries in contact per mean fiber area (index of potential perfusion) is significantly greater (25%) in winter muscles.
Multiple-coupled pacemaker system in renal pelvis of the unicalyceal kidney
Authors: Constantinou C. E. , Yamaguchi O.
Published: December 2017

The characteristics of spontaneous contractility in the renal pelvis were examined in the unicalyceal kidney of the rabbit. In vitro isometric studies were done on whole as well as renal pelvic segments dissected longitudinally and radially. The results show that the contractile frequency of isolated segments was highest in the proximal region (4.188 +/- 0.162 min-1) and decreased distally to (2.178 +/- 0.330 min-1). There was no significant frequency gradient in the circumferential direction. A modulation of wave form (waxing and waning phenomena) was observed in both the proximal and middle regions of the pelvis. Based on these results, a simulation of the renal pelvic activity was made by using a chain of coupled linear oscillators. At high values of coupling a pacemaker contraction of the renal pelvis was reproduced by the coupled oscillator model. The modulation of wave form was observed when the coupling of the circumferential direction was weak. These results are discussed in the context of the hierarchically organized multiple-coupled pacemaker system, which characterizes an integrative activity of the unicalyceal renal pelvis.
Absence of endotoxin fever but not prostaglandin E2 fever in the Brattleboro rat
Authors: Eagan P. C. , Kasting N. W. , Veale W. L. , Cooper K. E.
Published: December 2017

Changes in colonic temperature following intracerebroventricular injection (icv) of bacterial endotoxin or prostaglandin E2 (PGE2) were measured in Long-Evans (LE) and Brattleboro (DI) rats. Indwelling cannulas were implanted into the brains of rats for subsequent microinjection into a lateral cerebral ventricle. Microinjection of 1 microgram of bacterial endotoxin into a lateral cerebral ventricle produced a fever in the LE rat but not in the DI rat. Daily injections of 1 microgram of endotoxin icv in the DI rat did not result in a fever. Intraperitoneal injections of 50 micrograms of bacterial endotoxin resulted in a fever in the LE rat, but the DI rat showed no such response. Both groups of animals did produce a fever in response to icv administration of 200 ng of PGE2. The lack of arginine vasopressin in the DI rat may be related to the animal's failure to show a febrile response to endotoxin.
Metabolic and acid-base changes during selection of warmer water by cold-acclimated fish
Authors: Crawshaw L. I. , Ackerman R. A. , White F. N. , Heath M. E.
Published: December 2017

Largemouth bass (Micropterus salmoides) acclimated to 3 degrees C were placed in a thermal gradient. The bass selected the final thermal preferendum of 28 degrees C in about 18 h. The movement into warmer water was initially rapid but became progressively slower. 2) Other bass were acclimated to 8 degrees C, cannulated in the dorsal aorta, and placed in a temperature-controlled chamber. Oxygen uptake, blood pH, and total CO2 were measured as the chamber temperature was increased to 28 degrees C following a time course similar to that followed by bass in the gradient. 3) Oxygen uptake was always elevated above the resting level, and this elevation increased as higher temperatures were encountered. 4) Just prior to placement in the chamber the pH of the arterial blood was 7.98 +/- 0.05 (mean +/- SE). As the temperature was increased neither the pH nor the total CO2 content of the blood exhibited major changes. At temperatures between 26 and 28 degrees C, the pH (8.01 +/- 0.03) was about 0.3 pH units above predicted normal values. 5) During the return to the final thermal preferendum fish experience overall metabolic rates and extracellular acid-base levels that deviate progressively farther from normal resting levels. Neither factor appears likely to be the major determinant of the behavioral response.
Models' limits suggest reflexivity in nature
Authors: Fethe H.
Published: December 2017

A pattern may be seen among models from the physical, natural, and social sciences. The pattern derives from the hierarchical level of complexity of the phenomenon modeled, relative to the human modeler. Rigor decreases as models treat natural events progressively closer to the full complexity of the human. "Rigor" here is determined entirely by the conventional indicators of the scientific community; "complexity" refers to hierarchical level. This pattern of decreasing rigor is analogized to a limiting feature of formal systems: reflexivity. The scientific method of inquiry is observed to assume lawfulness in nature; lawfulness without reflexivity is suggested to be a dilemma. The gradient of rigor observed among models is suggested to be necessary, stable, and homeostatic. Consequently, reflexivity in nature is adopted as the most satisfactory metadisciplinary null hypothesis.
Peripheral neural input to neurons of the stellate ganglion in dog
Authors: Bosnjak Z. J. , Seagard J. L. , Kampine J. P.
Published: December 2017

In vitro and in vivo studies were conducted on the stellate ganglion (SG) of the dog by recording action potentials from its nerves and its neurons. For in vitro preparations, the SG and its nerve trunks were dissected from the animal and secured in an organ bath. Peripheral input to the SG was produced by electrical stimulation of the ventral ansa subclavia (VA), dorsal ansa subclavia (DA), and stellate cardiac nerve (SC) in 15 ganglion preparations studied in vitro. Electrical stimulation of the VA elicited action potentials recorded at the DA. This conducting pathway did not involve direct anatomic continuity, since the evoked potentials were blocked by injection of hexamethonium chloride into the SG. Most neurons in the SG received synaptic input from fibers of both central and peripheral origin. In 12 in vivo preparations, all nerves to the SG except the VA were cut. When peripheral sympathetic afferent input to the SG was increased, some of the postganglionic fibers of the dissected DA exhibited an increase in efferent nerve discharge. This response was also blocked by hexamethonium chloride. These results indicate that some of the functions of the SG might be independent of the central nervous system.
Phylogenesis of the Bainbridge reflex
Authors: Boettcher D. H. , Zimpfer M. , Vatner S. F.
Published: December 2017

The effects of volume loading were examined on measurements of left ventricular (LV) pressure and heart rate in patients undergoing cardiac catheterization. These data were compared to those collected in conscious dogs and subhuman primates (baboons). In man acute volume loading increased LV end-diastolic pressure by 14 mmHg, but did not increase LV systolic pressure significantly. Similar increases in LV end-diastolic pressure were observed in conscious dogs and baboons. LV systolic pressure also did not rise in baboons, but did increase (+32 mmHg) with volume loading in dogs. In man volume loading increased heart rate by 15 beats/min, significantly less (P less than 0.01) than observed in baboons (+37 beats/min), and which in turn was significantly less than that observed in dogs (+88 beats/min). Thus, the Bainbridge reflex, i.e., the tachycardia that occurs with volume loading, appears to exist in primates including man. However, the extent of utilization of this reflex decreases significantly from nonprimate mammals (dogs) to subhuman primates (baboons) to man.
L-leucine transport in liver of Antarctic fish in vivo at 0 degrees C
Authors: Haschemeyer A. E.
Published: December 2017

Uptake of L-[14C]leucine by liver of an endemic Antarctic fish, Trematomus hansoni, was studied by a single injection technique with [3H]inulin as a reference. Rate constants for leucine influx and efflux and incorporation into liver protein were determined by analysis of isotope distribution in the free and protein-bound compartments of liver and in blood draining the liver at various times after injection. Transport rates were slower than in temperate fish at 20 degrees C, but saturation properties and ability to accumulate leucine in liver were comparable. Kinetic analysis indicated that 30% of uptake at 0 degrees C was due to active transport, similar to that in toadfish at 20 degrees C. This contrasts with the absence of this component in toadfish cooled to 10 degrees C. Average polypeptide chain assembly time was 19 min at 0 degrees C. Transport functions were maintained in fish warmed to 10 degrees C; however, protein synthesis declined at temperatures above 5 degrees C. The results indicate this system is adapted to function at extremely low temperatures in a manner qualitatively similar to organisms adapted to much higher temperatures. Transport and synthetic rates, however, were low, consistent with a normal temperature dependency (Q10 about 2.5) for biological reaction rates.
Water regulation in weanling hypodipsic dorsomedial hypothalamic-lesioned rats
Authors: Bellinger L. L. , Bernardis L. L.
Published: December 2017

Weanling rats with dorsomedial hypothalamic nuclei lesions (DMN-L) are hypodipsic and hypophagic when compared to sham-operated rats. When tested for interdependence of food and water intake (WI) the DMN-L rats drank in the absence of food and ate in the absence of water. The data suggest DMN-L rats are not prandial drinkers. On testing for intracellular thirst (5.8 or 5.4% NaCl, 1 ml/100 g body wt), extracellular thirst [polyethylene glycol (PG), 25% wt/vol, 0.5 ml/35 g body wt], or a combination of both thirsts, the DMN-L rats responded as well or better than the control animals when the test data were expressed as a percentage of the rat's base-line WI. Both groups were more responsive to PG when tested in the light phase. When injected with angiotensin II (200 micrograms/100 g body wt) both groups responded similarly. Therefore, whereas the DMN-L rats were hypodipsic in comparison to controls, they respond as well or better than control animals when classical thirst testing procedures are utilized. It is suggested that DMN-L may have "reset" WI similarly to the previously proposed reset for body weight and food intake.
Role of macula densa in renal nerve modulation of renin secretion
Authors: Osborn J. L. , Thames M. D. , DiBona G. F.
Published: December 2017

Low-frequency renal nerve stimulation (0.25 Hz) augments the renin secretion response to reduction of renal perfusion pressure to 50 mmHg by aortic constriction. The present experiments determined whether this modulating influence could be demonstrated when the macula densa receptor was inoperative. In 10 anesthetized dogs with a nonfiltering kidney and sectioned renal nerves, aortic constriction to 52 mmHg decreased renal blood flow and increased renin secretion from 126 +/- 94 to 192 +/- 55 ng/min. During low-frequency renal nerve stimulation and aortic constriction to 50 mmHg, renin secretion was not augmented (37 +/- 13 to 81 +/- 42 ng/min). In four anesthetized dogs with nonfiltering kidneys, aortic constriction to 52 mmHg increased renin secretion similarly before (16 +/- 8 to 68 +/- 17 ng/min) and after renal denervation (14 +/- 14 to 78 +/- 18 ng/min). Therefore, the augmentation of the renin secretion response to aortic constriction to 50 mmHg by low-frequency renal nerve stimulation in filtering kidneys does not result from an interaction with the renal vascular baroreceptor or the juxtaglomerular granular cells. Since neural augmentation of renin secretion during aortic constriction was not observed in the nonfiltering kidney where the macula densa is inoperative, we conclude that the macula densa is the probable site for the neural modulation of renin secretion.
Comment on "Parameter and structural identifiability concepts and ambiguities: a critical review and analysis"
Authors: Godfrey K. R.
Published: December 2017

Identifiability of a model for the glucose tolerance test, considered by Cobelli and DiStefano [Am. J. Physiol. 239 (Regulatory Integrative Comp. Physiol. 8): R7-R24, 1980], is shown to depend on the shape of the external perturbation. For systems with two or more inputs applied simultaneously, it is essential in Laplace transform identifiability analysis to examine the Laplace transform(s) of the observation(s) rather than the individual transfer functions, which are not measurable separately.
Glucose and lactate kinetics and interrelations in an antarctic bird (emperor penguin)
Authors: Groscolas R. , Rodriguez A.
Published: December 2017

The isotope single-injection method was used to investigate the glucose and lactate kinetics and the interrelationships between the glucose and lactate pools in fasting emperor penguins. In these remarkably fast-resistant birds, mean lactate concentration, replacement rate, pool, space, and transit time were 1.5 mmol.1-1,53 mumol.min-1.kg-1, 900 mumol.kg-1, 60% of body mass, and 17 min, respectively. Mean glucose concentration, replacement rate, pool, space, and transit time were 20 mmol.1-1, 23 mumol.min-1.kg-1, 4,300 mumol.kg-1, 24% of body mass, and 196 min, respectively. Maximum conversions of lactate into glucose and of glucose into lactate were 29 +/- 2.9% and 75.5 +/- 4.2%, respectively, which indicates that lactate is an effective gluconeogenic precursor and a major fate of glucose metabolism in fasting penguins. The lactate replacement rate and incorporation into glucose were related to the plasma lactate concentration, which suggests that the rate of formation of glucose from lactate is dependent on the availability of lactate. The glucose replacement rate and reduction into lactate were related with the plasma glucose concentration, suggesting that the rate of lactate formation from glucose is dependent on the plasma glucose concentration. These data suggest that in the fasting emperor penguin glucose and lactate availability is capable of regulating the rate at which these substrates are utilized and interconverted. To our knowledge, this is the first evidence for such regulatory capacities in birds.
Noncompartmental vs. compartmental analysis: some bases for choice
Authors: DiStefano J. J.
Published: December 2017

The physical conditions that govern the applicability of noncompartmental analysis methods apparently are not all completely appreciated in the user community. This increasingly popular approach to kinetic analysis is not "model independent," as it is often called, and if it is used, for example, for substances synthesized in pools not accessible to direct test-input probes, or substances metabolized in pools inaccessible to direct measurement, results will be more or less in error. STrictly speaking, all endogenous sources (e.g., secretions) and all sinks (e.g., catabolism) each must be uniquely associated with the same (central) pool(s) into which test inputs are introduced, the same pool(s) where all measurements must be made. The consequences of not meeting these conditions are explored by evaluating the errors committed in estimating distribution volumes VD, plasma (metabolic) clearance rates PCR, and mean residence or transit times t, in mammillary-connected systems of arbitrary size (as an example), in which sources and sinks exist in one or more noncentral pools. It is shown that noncompartmental analysis always underestimates VD and t under any such conditions, and PCR is underestimated if there are noncentral sources. Formulas for the errors are given, which could be large or small depending on several complex factors not easy to discern without additional information about the system.
Increased heat loss in ovariectomized hypothyroid rats treated with estradiol
Authors: Laudenslager M. L. , Carlisle H. J. , Calvano S. E.
Published: December 2017

The role of the thyroid in the mediation of an estrogen-associated change in thermal balance was studied in thyroidectomized and in propylthiouracil-treated ovariectomized rats. Prior to propylthiouracil treatment, estrogen-treated ovariectomized rats and intact female rats had higher rates of heat production and dry heat loss at -5 degrees C than ovariectomized rats. Heat production of estrogen-treated and intact female rats was well below their rates of dry heat loss without an alteration in the absolute rate of heat loss in the hypothyroid condition. Heat production exceeded heat loss only in the hypothyroid ovariectomized group not receiving estrogen. Ovariectomized rats without estrogen maintained thermal balance, whereas rectal temperatures fell in both intact and estrogen-treated ovariectomized rats during cold exposure. Increased heat loss unbalanced by heat production was also observed in surgically thyroidectomized estrogen-treated ovariectomized rats tested at -5 degrees C. These results suggest that an estrogen-induced increase in heat loss, which is compensated by an increase in heat production in the euthyroid but not the hypothyroid condition, is one mechanism responsible for estrogen-associated changes in thermal balance during cold exposure.
Metabolic and hormonal changes following endotoxin administration to diabetic rats
Authors: Kelleher D. L. , Fong B. C. , Bagby G. J. , Spitzer J. J.
Published: December 2017

The aim of these investigations was to study the time course and cause of the altered metabolic response of diabetic rats to endotoxin administration. Escherichia coli endotoxin was administered to streptozotocin-diabetic and control normoglycemic rats. At 1, 2, 5, 8, and 24 h following endotoxin, animals were decapitated. Plasma samples were analyzed for glucose, lactate, insulin, glucagon, and corticosteroids. In addition, tissue glycogen content of liver and skeletal muscle was determined. Endotoxin caused an elevation of plasma glucose in both diabetic and normoglycemic rats by 1 h postinjection. The elevation was prolonged in diabetic rats for 8 h but lasted only 2 h in nondiabetic rats. Both endotoxin-treated groups demonstrated hyperlactacidemia following endotoxin. Endotoxin led to liver glycogen depletion in both diabetic and normoglycemic rats, whereas muscle glycogen content was only slightly affected. Plasma glucagon and corticosteroids rose immediately and remained elevated in both endotoxin-treated groups. A significant insulin response to rising plasma glucose was observed in nondiabetic but not in diabetic rats following endotoxin. These results suggest that the exaggerated and prolonged hyperglycemia observed in diabetic endotoxin-treated rats is due to hypersecretion of glucose-mobilizing hormones and elevated gluconeogenesis, unmatched by an adequate secretion of insulin to promote glucose uptake and utilization.
Oral antidiuretic therapy: studies in the diabetes insipidus rat
Authors: Kinter L. B. , Beeuwkes R.
Published: December 2017

In hypothalamic diabetes insipidus, water balance is achieved primarily through the thirst mechanism. The administration of an antidiuretic agent in the drinking water should restore the antidiuretic response to volume and osmoregulatory drive. To test this hypothesis, homozygous Brattleboro strain rats were given arginine vasopressin (AVP) or 1-desamino-8-D-arginine vasopressin (dDAVP) in the drinking water in concentrations of 10–10,000 micrograms/l (AVP) and 5–10,000 micrograms/l (dDAVP). Oral AVP was found to be ineffective. Oral dDAVP resulted in 1) a progressive increase in dDAVP dose, from 2.3 to 2,559 micrograms.day-1.kg-1; 2) a dose-dependent increase in urine osmolality from 306 to 1,796 mosmol/kg; and 3) a dose-dependent decrease in urinary solute excretion. At each dDAVP dose level, stable physiological states were achieved within 24 h. Similar antidiuretic states were achieved when dDAVP was administered in increasing doses or when therapy was initiated at a high dose. These findings demonstrate that inclusion of an appropriate antidiuretic agent in the drinking water can restore the renal response to volume-osmoregulatory drive.
Mechanism and control of salt absorption in locust rectum
Authors: Hanrahan J. , Phillips J. E.
Published: December 2017

The rectum is the main reabsorptive site in the excretory system of locusts. The primary urine entering this organ from the Malpighian tubules is rich in K+ (140 mM) and Cl- (90 mM), and most of this fluid is normally reabsorbed. Fluid and active Cl- reabsorption in the rectum are regulated by neuropeptide hormones from the corpus cardiacum. We have studied the mechanism of KCl reabsorption using voltage clamp, tracers, double-barreled ion-sensitive microelectrodes, and ion substitutions. Locust Cl- absorption differs from vertebrate systems in that it is not dependent on Na+ or HCO-3/CO2, and it is insensitive to normal inhibitors of Cl- transport. Entry of Cl- into rectal cells is active, electrogenic, and stimulated by luminal K+. This cation substantially increases the electrochemical gradient across the apical membrane against which Cl- is pumped; therefore K+ does not act solely and indirectly by electrical coupling. Kinetic studies also suggest that K+ activates the Cl- pump. Consequently at least two levels of control are exerted during cAMP stimulation; K+ permeability of the epithelium and the transepithelial potential generated by active Cl- transport both increase. The enhanced net K+ absorption from the lumen side after stimulation is largely passive, being electrically coupled to Cl- transport. However, this general increase in KCl absorption is "fine tuned" by K+ itself, through its direct effect on the Cl- pump.
Electrophysiology of chloride transport in Aplysia (mollusk) intestine
Authors: Gerencser G. A.
Published: December 2017

This investigation was principally undertaken to examine the mechanism of Cl- transport across the Aplysia californica intestinal epithelium. Previous results have shown: 1) the transmural potential difference (psi m leads to s) and the mucosal membrane potential difference (psi m) to be negative relative to the mucosal solution, 2) mucosal D-glucose hyperpolarized psi m leads to s and depolarized psi m, 3) mucosal D-glucose significantly increased intracellular Cl- activity (aiCl), however the electrochemical potential (-mu i) for intracellular Cl- was significantly less in both cases, than the -muCl in the mucosal solution, 4) replacing Cl- in the bathing medium with SO-4(2) significantly reduced both psi m and psi m leads to s, and 5) the energy within the electrochemical potential difference for Na+ (delta -mu Na) directed from mucosa to cytosol was energetically adequate so that intracellular Cl- accumulation could occur. New results showed: 1) psi m and psi m leads to s to significantly hyperpolarize when Na+ was replaced with Tris+ in the bathing medium, 2) aiCl decreased from 13.9 +/- 0.5 to 9.1 +/- 0.3 mM when Na+ was replaced with Tris+ in the bathing medium. The intracellular -muCl, both in the presence and absence of Na+, was significantly less than -muCl in the mucosal medium. These results suggest that Na+ and Cl- transport across the mucosal membrane are not mechanistically coupled and that an active extrusion mechanism for Cl- exists in the lateral-serosal membrane of the surface epithelial cells of A. californica intestine.
Thermoregulatory heat production in cold-reared and warm-reared pigs
Authors: Heath M. , Ingram D. L.
Published: December 2017

Pigs were reared from 2 wk of age in either 10 or 35 degrees C and fed ad libitum. At 8 wk of age they were tested for the presence of regulatory nonshivering thermogenesis by administration of norepinephrine (NE) and propranolol. In addition, an electromyogram and carotid temperature, as well as a heat flow and skin temperature from one site, were monitored while the pigs were at ambient temperatures of 10, 15, 20, 25, and 30 degrees C. Cold-reared pigs showed a heightened response to NE in cold compared to thermally neutral environments. This was not observed in warm-reared pigs. Propranolol depressed O2 consumption more in cold-reared than in warm-reared pigs. Pigs reared in the cold also showed a higher intensity of shivering, tissue conductance, and skin temperature than warm-reared littermates. The shivering response of cold-reared pigs was more sensitive to changes in skin temperature than in warm-reared pigs.
Na+ absorption in Aplysia intestine: Na+ fluxes and intracellular Na+ and K+ activities
Authors: Gerencser G. A.
Published: December 2017

Microelectrodes were used to measure the potential difference (psi m) across the mucosal membrane of epithelial cells lining the villi of isolated Aplysia californica intestine. In substrate-free NaCl seawater medium psi m was -55.1 +/- 1.2 mV. The cell interior was negative relative to the mucosal bathing solution. Intracellular K+ activity, determined in the absorptive cells with single-barreled liquid ion-exchanger microelectrodes, was 383 +/- 15 mM. Since the calculated K+ equilibrium potential exceeds the membrane potential, K+ is accumulated by the intestinal absorptive cell. Intracellular Na+ activity (aiNa) was also determined in the intestinal cells of Aplysia with single-barreled liquid ion-exchanger microelectrodes and was 17.2 +/- 2.5 mM. aiNa was much less than that predicted by the electrochemical equilibrium value for Na+ across the mucosal membrane. From these data the steady-state transapical Na+ and K+ electrochemical potential differences were calculated. Serosal ouabain abolished net sodium absorption as determined by flux measurements. These results are consistent with the operation of a basolateral Na+ - K+ pump.
Regulation of angiotensinogen in cerebrospinal fluid and plasma of rats
Authors: Schelling P. , Muller S. , Clauser E.
Published: December 2017

The origin and regulation of angiotensinogen in cerebrospinal fluid (CSF) was investigated in rats by measuring renin substrate in plasma and CSF under different experimental conditions. Nephrectomy (NX) increased the circulating and the central angiotensinogen levels. There was no correlation between the individual values of plasma and CSF. Adrenalectomy (ADX) diminished and hydrocortisone treatment augmented the angiotensinogen levels in plasma and CSF. The combination of ADX and NX caused a dissociation between peripheral and central angiotensinogen, since the values were elevated in plasma but unchanged in CSF. After the application of the converting-enzyme inhibitor captopril a significant decrease of angiotensinogen was observed in plasma only. A specific radioimmunoassay for renin substrate of rat plasma also recognized CSF angiotensinogen. There was a linear correlation between the CSF substrate levels obtained by direct and indirect measurement. In conclusion, CSF angiotensinogen appears to be immunologically similar to the plasma molecule. The angiotensinogen levels in CSF and plasma may be affected in parallel but can nevertheless be dissociated from each other.
Drinking and pressor responses after acetylcholine injection into subfornical organ
Authors: Mangiapane M. L. , Simpson J. B.
Published: December 2017

Mean arterial pressure and drinking were measured in rats before and after intracranial injection of acetylcholine (ACh) into the subfornical organ (SFO), the circumventricular organ of the dorsal third ventricle. Arterial pressure was recorded in unanesthetized unrestrained animals by means of an abdominal aortic catheter. Maximal increases in arterial pressure and drinking followed the application of ACh to SFO, while significantly smaller effects were obtained after ACh injections into near-SFO control sites. Inasmuch as the effects also occurred with the shortest latencies after SFO injections, the possibility of ACh diffusing to act at other than SFO sites seems unlikely. The pressor and drinking responses to ACh were blocked by SFO pretreatment with atropine, indicating muscarinic receptor involvement. The SFO-mediated pressor response to ACh was reduced after systemic injection of phentolamine, suggesting at least a partial role for the sympathetic nervous system in the response. The present experiments suggest that ACh acts at the SFO to generate not only drinking but also increases in arterial pressure.
Ketone-glucose interaction in fed, fasted, and fasted-infected sheep
Authors: Radcliffe A. G. , Wolfe R. R. , Colpoys M. F. , Muhlbacher F. , Wilmore D. W.
Published: December 2017

Ketosis following starvation was suppressed by hindlimb infection in seven fasted sheep. Glucose production determined following the primed constant infusion of [6-3H(N)]glucose was elevated in the fasted-infected animals (9.50 +/- 1.11 mmol X kg-1 X min-1 (mean +/- SE) versus fasted controls (5.56 +/- 2.2). To determine if the ketonemia following sepsis contributed to the increased glucogenesis associated with catabolic disorder, glucose production and arterial substrates were measured before and after infusion of sodium-DL-beta-hydroxybutyrate (beta-OHB, 20 mumol X kg-1 X min-1) in fed, fasted, and fasted-infected animals. Following 3 h of beta-OHB infusion in the awake conditioned animals, beta-OHB and acetoacetate blood concentrations more than doubled. With infusion, blood glucose and alanine concentrations decreased in the fed and fasted sheep but not in the fasted-infected group. Glucose production fell significantly from 10.11 +/- 1.33 to 8.44 +/- 1.05 in the fed animals and from 5.05 +/- 0.28 to 4.11 +/- 0.33 in the fasted group. Glucose production was unaffected by beta-OHB infusion in the fasted-infected animals (9.50 +/- 1.83 vs. 9.11 +/- 1.44). The accelerated rate of glucose production in sheep following infection is not a consequence of the hypoketonemic state associated with sepsis.
Sodium excretion following lesions of preoptic recess periventricular tissue in the rat
Authors: Bealer S. L.
Published: December 2017

Electrolytic lesions of periventricular tissue surrounding the anteroventral third ventricle (AV3V) results in chronic hypernatremia and attenuates natriuresis following several experimental treatments. The present investigation was designed to determine if AV3V periventricular ablation results in acute postlesion alterations in sodium metabolism. Urinary sodium excretion was measured during 2-h periods for 6 h, and then daily for 7 days following either electrolytic ablation of AV3V periventricular tissue or control surgery. Similar measurements were carried out on unoperated control animals, and rats which had received either renal denervations or subcutaneous injections of deoxycorticosterone (DOC) prior to surgery. Lesions of the tissue surrounding the AV3V resulted in a natriuresis and polyuria that was not prevented by renal denervation or DOC treatment and was accompanied by a pressor response and decreased glomerular filtration rate. The initial natriuresis was followed by 2 days of sodium retention, which exceeded the amount necessary to restore sodium balance. These data demonstrate that ablation of AV3V periventricular tissue results in acute alterations in sodium metabolism, and support the hypothesis that tissue surrounding the AV3V contains neural elements critical for normal sodium regulation.
Effect of nutrient density and composition of liquid meals on gastric emptying in feeding rats
Authors: Kalogeris T. J. , Reidelberger R. D. , Mendel V. E.
Published: December 2017

Rats were fitted with gastric cannulas to determine gastric emptying rates of liquid test meals after a 16-h fast. They were allowed to drink [14C]polyethylene glycol (PEG) Vivonex High Nitrogen elemental diet (VHN) or Intralipid Fat Emulsion (IL) at 0.25, 0.50, and 1.00 kcal/ml under two conditions: drinking to satiety (VHN) or drinking to a constant volume of 15 ml (VHN and IL). Recovery of stomach contents through the cannula at the end of the drinking period allowed determination of rate of emptying. Average gastric emptying rate (ml/min) during a meal was found to vary inversely with the nutrient density of the test meal. However, the caloric emptying rate (kcal/min), as well as the total caloric load delivered to the intestine by the end of the meal, remained constant over the range of nutrient densities tested. The constancy of caloric emptying rate as diet caloric density increased was independent of diet composition, supporting the hypothesis that rate of gastric emptying is determined by caloric density of the diet. When rats were allowed to drink to satiety, caloric intake was not regulated but increased with increasing diet nutrient density, suggesting that control of meal size was independent of regulation of gastric emptying.
Umbilical glucose and lactate extractions during maternal hyperglycemia in sheep
Authors: Crandell S. S. , Palma P. A. , Morriss F. H.
Published: December 2017

Umbilical glucose and lactate extractions were determined in previously instrumented pregnant ewes into some of which D-glucose was infused to produce graded levels of maternal hyperglycemia as great as 20 mM. While fetal arterial glucose concentration continued to increase linearly as a function of maternal arterial glucose concentration during maternal hyperglycemia, the umbilical venoarterial difference in blood glucose concentration did not, and umbilical glucose extraction approached a plateau at approximately 0.063 mmol X min-1 X kg fetus-1 at maternal glucose concentrations greater than approximately 8 mM. The observed plateau in glucose extraction is consistent with saturation at high maternal glucose concentrations of the carrier mechanism for transport of glucose from the maternal to the fetal aspects of the trophoblast. The observed value of the plateau in umbilical extraction of glucose is slightly less than the maximum extraction predicted from previously published equations for this species, but the maternal blood glucose concentration at which the observed maximum occurred agrees closely with the value predicted by those equations. Umbilical lactate extraction, 0.031 +/- 0.021 mmol X min-1 X kg fetus-1, was independent of maternal arterial blood glucose and lactate concentrations and was independent of umbilical glucose extraction.