bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptations to chloride-depletion alkalosis
Authors: Galla J. H. , Gifford J. D. , Luke R. G. , Rome L.
Published: December 2017

The systemic and renal adaptations for the maintenance and correction of metabolic alkalosis generated by chloride depletion (CDA) are the focus of this review. The hypothesis that extracellular fluid (ECF) volume expansion is essential for the correction of CDA is refuted, while the concept that Cl- repletion is necessary and sufficient for correction is developed. Contraction of ECF volume probably can occur as a consequence of CDA. The principal mechanisms by which the kidney corrects CDA appear to reside primarily in the collecting duct, which is endowed with the anion exchange mechanisms and the capacity to effect the necessary changes in body anion composition. Although the remainder of the collecting duct is undoubtedly important in this response, the cortical segment appears to have the paramount role since it can either absorb or secrete HCO3-. Alterations in the delivery of Cl- or HCO3- to the collecting duct may also be important but changes in glomerular filtration rate appear to have a minor role. Major unanswered questions in the pathophysiology of CDA are the manner in which exogenous Cl- repletion is detected and the kidney is signaled to excrete HCO3- and the cellular mechanisms by which this is accomplished in the various nephron segments.
Defective cerebral glucose utilization in diet-induced obese rats
Authors: Levin B. E.
Published: December 2017

A neural mechanism may underlie the divergent weight gain patterns of rats fed a high-energy diet; half develop diet-induced obesity (DIO), whereas the rest are diet resistant (DR). Male rats were fed chow (n = 14) or a high-energy diet for 3 mo with the development of DIO (n = 11) or DR (n = 12). DIO rats had 159-219% heavier retroperitoneal fat pads and 158% higher plasma insulin levels than chow-fed and DR rats, but plasma glucose levels were equal. Rats were trained to drink glucose after an overnight fast and were tested for local cerebral glucose utilization using 2-deoxy-D-[14C]glucose autoradiography in the presence or absence of 0.15% saccharin substituted for glucose. Saccharin intake increased 2-deoxyglucose uptake in the rostral nucleus tractus solitarius of DR but not DIO or chow-fed rats. Also, DIO rats had reduced basal 2-deoxyglucose uptake in the central amygdaloid nucleus. High-energy diet intake was associated with saccharin-induced depression of 2-deoxyglucose uptake in the inferior olive and increased utilization in the medial amygdaloid nucleus of both DR and DIO rats. Thus DIO rats have diminished basal and food-related neuronal activity in certain brain areas involved in food intake and autonomic function. Furthermore, dietary content affects glucose utilization in areas not usually associated with these functions.
Atrial natriuretic peptide and renal cGMP in rats with experimental heart failure
Authors: Abassi Z. , Burnett J. C. , Grushka E. , Hoffman A. , Haramati A. , Winaver J.
Published: December 2017

Rats with chronic aortocaval (AV) fistula, an experimental model of congestive heart failure, display high plasma levels of atrial natriuretic factor (ANF) and a blunted natriuretic response to ANF infusion. We previously reported that rats with AV fistula either develop progressive sodium retention (urinary sodium excretion, UNaV less than 100 microeq/24 h) or compensate (UNaV greater than 1,200 microeq/24 h). To gain further insight into the mechanism of renal hyporesponsiveness to ANF, we evaluated the effect of ANF on renal guanosine 3',5'-cyclic monophosphate (cGMP) production in sham-operated control rats and in the two groups of rats with AV fistula. Infusion of synthetic ANF-(99-126) (at either 10 or 50 micrograms.kg-1.h-1) resulted in a reduced fractional sodium excretion (P less than 0.05) in both compensated rats (0.7 +/- 0.2 and 7.9 +/- 1.6%) and sodium-retaining rats (0.3 +/- 0.1 and 0.5 +/- 0.1%) compared with controls (8.5 +/- 1.2 and 13.7 +/- 2.3% for low and high doses, respectively). Similarly, urinary cGMP excretion corrected by glomerular filtration rate (UcGMPV/GFR) during low-dose ANF infusion was significantly reduced (P less than 0.05) in both groups with AV fistula (compensated: 39 +/- 10 pmol/ml; sodium-retaining: 55 +/- 13 pmol/ml) compared with controls (115 +/- 16 pmol/ml). During high-dose ANF infusion, compensated rats, but not sodium-retaining rats, displayed a significant increase in UcGMPV/GFR. The differences in UcGMPV/GFR are probably not due to variations in urine flow because furosemide infusion to a separate group of rats with AV fistula increased urine flow approximately eightfold but did not increase UcGMPV/GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of carotid baroreflex control of plasma AVP concentration in conscious and anesthetized dogs
Authors: Wehberg K. E. , Gala G. J. , Brunner M. J.
Published: December 2017

We compared carotid sinus baroreflex control of endogenous plasma arginine vasopressin (AVP) in chronically prepared conscious and acutely prepared anesthetized dogs. The carotid sinuses of both conscious and pentobarbital-anesthetized dogs were isolated bilaterally and perfused at constant pressures. Carotid sinus pressure (CSP) was changed between 200 and 50 mmHg in 25-mmHg steps in intact conscious and anesthetized dogs. Similar runs were repeated after vagotomy. Mean arterial pressure (MAP) and heart rate (HR) were monitored. At each interval of CSP, blood was withdrawn for AVP analysis by radioimmunoassay. MAP responses to changes in CSP were not different in the four experimental groups. Both anesthesia and vagotomy increased the HR responses to changes in CSP. With vagi intact, AVP increased at high CSP in conscious but not in anesthetized dogs. After vagotomy, low CSP led to an increase in plasma AVP that did not differ between conscious and anesthetized dogs. The results suggest that the release of AVP is modulated by the action of the carotid baroreflex as a normal component of an integrated efferent response. The response is similar in conscious and pentobarbital-anesthetized dogs and is normally buffered by reflexes with vagal afferents.
Sympathoadrenal-circulatory regulation during sustained isometric exercise in young and older men
Authors: Taylor J. A. , Hand G. A. , Johnson D. G. , Seals D. R.
Published: December 2017

The aim of this study was to test the hypothesis that the arterial blood pressure, vasoconstrictor, and sympathoadrenal adjustments to sustained submaximal isometric exercise become augmented with advancing age in humans. Fourteen young (26 +/- 1 yr) and 14 older (66 +/- 1 yr) healthy males performed isometric handgrip exercise at 30% of maximal voluntary force until exhaustion (inability to maintain target force). Maximal handgrip force was quite similar in the young and older subjects (402 +/- 20 vs. 392 +/- 20 N, respectively). The two groups did not differ significantly on any variable at rest. During sustained handgrip to exhaustion, peak levels of both perceived exertion and contracting forearm electromyographic activity were similar in the young and older men, suggesting equivalent voluntary efforts. Exercise time was not different in the two groups (315 +/- 27 s in young vs. 339 +/- 17 s in older men). Throughout exercise the increases in arterial blood pressure were very similar in the young and older subjects. Heart rate increased less (P less than 0.05), but stroke volume (impedance cardiography) tended to decrease less (not significant) in the older men; thus the increases in cardiac output were not different in the two groups. During the latter portion of exercise, systemic vascular resistance tended to increase in both the young and older men, with no significant group differences. The blood flow responses in the whole calf (venous occlusion plethysmography) and the calf skin (laser-Doppler velocimetry) were similar in the young and older subjects, as were the corresponding increases in vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic anemia in pregnant ewes: maternal and fetal effects
Authors: Mostello D. , Chalk C. , Khoury J. , Mack C. E. , Siddiqi T. A. , Clark K. E.
Published: December 2017

To examine maternal and fetal responses to a sustained reduction in maternal hematocrit during days 110-138 of ovine gestation, 22 ewes and their singleton fetuses were instrumented. By repetitive exchange transfusions, the hematocrit in 12 ewes was decreased from 28.1 +/- 0.8 (baseline, day 110) to 14.0 +/- 0.7% (day 117) and maintained at that level. Anemic ewes demonstrated a transient increase in heart rate from 99 +/- 4 to 116 +/- 4 beats/min and a sustained increase in cardiac output from 117 +/- 8 to 153 +/- 11 ml.min-1.kg-1 compared with control animals. Uterine blood flow steadily increased in control animals from 868 +/- 100 (day 110) to 1,410 +/- 177 ml/min (day 138) but failed to increase in the anemic ewes. Uterine oxygen delivery fell from 83 +/- 10 to 39 +/- 4 ml/min with production of anemia and remained low in the anemic ewes. Arterial PO2 and oxygen content in the fetuses of anemic ewes fell transiently below control values (19.9 +/- 0.8 vs. 23.4 +/- 1.0 mmHg and 5.3 +/- 0.3 vs. 6.8 +/- 0.4 ml/dl, respectively) but did not persist. Fetal weights at 138 days gestation were lower in the anemic group (2,596 +/- 329 vs. 4,313 +/- 132 g). We conclude that chronic maternal anemia results in a decreased uterine blood flow as well as decreased uterine oxygen delivery. The fetus responds with decreased growth but does not develop sustained hypoxia or acidosis.
Enhanced acceptance and metabolism of fats by rats fed a high-fat diet
Authors: Reed D. R. , Tordoff M. G. , Friedman M. I.
Published: December 2017

Rats fed a high-fat diet show greater acceptance of and preference for pure fats than do rats fed a high-carbohydrate diet. We tested the hypothesis that this differential intake of fat was due to diet-induced modifications of lipid absorption and oxidation. After an intragastric load of corn oil, rats adapted to a high-fat diet had greater increases in plasma triglyceride and ketone levels and a lower percentage of fecal fat than did rats adapted to an isocaloric high-carbohydrate diet. High-fat-fed rats given corn oil containing [14C]palmitic acid expired 14CO2 more rapidly and to a greater extent than did rats maintained on a high-carbohydrate diet. These results show that the greater acceptance of fat by rats fed a high-fat diet is associated with an increased capacity to absorb and oxidize fat.
Differential effects of cytokines on thermosensitive neurons in guinea pig preoptic area slices
Authors: Shibata M. , Blatteis C. M.
Published: December 2017

This study was undertaken to determine whether the reported different courses of the febrile responses to the cytokines interleukin-1 beta (IL-1), interferon-alpha 2 (IFN), and tumor necrosis factor-alpha (TNF) might have neuroelectrophysiological correlates. The reactions of individual thermosensitive neurons in the preoptic area (POA) were evaluated by recording their extracellular single-unit firing rates (FR) in slices of guinea pig POA perfused with artificial cerebrospinal fluid (aCSF), human recombinant IL-1 (50-500 ng), IFN (1,000-8,000 U), and TNF (400-5,000 ng) (all doses per min/ml aCSF); thermosensitivity was assessed by FR responses to changes of perfusate temperature (32-42 degrees C). Overall, these cytokines depressed the FR of warm-sensitive units and excited those of cold-sensitive units, in agreement with expectations. However, the responses of individual neurons treated with two or all three cytokines were dissimilar: 61% of the units tested reacted differentially to two or three cytokines, 32% exhibited identical responses, and 7% had no response to any cytokine. These results support the possibility that IL-1, IFN, and TNF may affect not the same but rather distinct neurons functionally connected to common pyrogenic effectors. Thus they suggest that differential neuronal substrates may be utilized by each cytokine to exert its pyrogenic effect.
Effects of vasopressin on arterial blood pressure and cardiac output in male and female rats
Authors: Toba K. , Crofton J. T. , Inoue M. , Share L.
Published: December 2017

This study was performed to investigate further the mechanisms underlying the sexual dimorphism of the pressor responses to vasopressin. We have confirmed our earlier findings that the pressor response to graded infusions of vasopressin in conscious unrestrained male rats is similar to that in estrous females and greater than in diestrus, proestrus, and metestrus. This difference was due primarily to greater increases in total peripheral resistance (TPR) in males and estrous females, since there were no sex- or cycle-related differences in the vasopressin-induced reductions in cardiac output. Gonadectomy was without effect in males but, in females, increased blood pressure responses to vasopressin to levels found in males. Chronic treatment of ovariectomized rats with estradiol reduced pressor responsiveness to vasopressin; treatment with progesterone was without effect. These differences were also due to differences in TPR. It is concluded that the sex- and cycle-dependent differences in vasopressin-induced increases in blood pressure are due largely to attenuation of increases in TPR by estrogen.
Is fetal acidosis in the human fetus maternogenic during labor? A reanalysis
Authors: Piquard F. , Schaefer A. , Dellenbach P. , Haberey P.
Published: December 2017

The purpose of this study was to investigate whether maternogenic fetal acidosis can occur at the time of labor and delivery and to evaluate the extent of the possible maternal contribution to fetal acidosis. We have therefore determined fetal and maternal lactate concentrations and acid-base status under various conditions in 589 women at the end of gestation and during labor. The results show that metabolic acidosis develops in all fetuses because of increased production of lactic acidosis is primarily of fetal origin: 1) the umbilical arteriovenous lactate differences were positive and large in steady-state conditions as well as in depressed newborns; 2) the conditions that could produce a net transfer of lactate from the mother to the fetus, namely a positive maternofetal gradient of lactate and proton, were rarely observed; and 3) the correlation between fetal and maternal lactate levels was very weak, with regression coefficients decreasing from near steady-state conditions to acute stress conditions, indicating that the increase in lactate in the fetus and mother occurs independently. This correlation indicates also that increased maternal lactate production under conditions of labor and delivery can make a contribution by affecting the rate of net transfer from fetus to mother. This is possible in approximately 6% of the fetuses.
Response of muscle protein synthesis to fasting in suckling and weaned rats
Authors: Davis T. A. , Fiorotto M. L. , Nguyen H. V. , Burrin D. G. , Reeds P. J.
Published: December 2017

Protein synthetic efficiency (KRNA) is low in immature skeletal muscle of suckling rats and increases toward the end of the suckling period. To determine whether immature skeletal muscle is able to further reduce KRNA in response to fasting, suckling (5, 10, and 16 days of age) and weaned (28 days of age) rats were fed, fasted for 10 h, or fasted for 18 h and injected with a flooding dose of L-[4-3H]phenylalanine for measurement of muscle protein synthesis in vivo. In fed rats, fractional rates of protein synthesis (KS) and protein synthetic capacity decreased during the suckling period. KRNA increased toward the end of the suckling period. In 5-day-old rats, fasting for 10 h produced a 50% decline in KS of extensor digitorum longus and plantaris muscles, but KS did not change further after 18 h of fasting. In older suckled and weaned rats, 10 h of fasting decreased KS of extensor digitorum longus and plantaris muscles 30%; after 18 h of fasting, values had declined to 50% of those in fed animals. The reductions in KS in soleus muscles with 10 and 18 h of fasting were similar to those in other muscles at 5 and 10 days but were less than those in other muscles at 16 and 28 days. Changes in KRNA were similar to those for KS in all muscles from all age groups fasted for 10 and 18 h. Protein synthetic capacity decreased approximately 12% after 18 h of fasting, but this effect did not differ between age groups or muscle types.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of food intake and body weight in rats by the synthetic heme analogue cobalt protoporphyrin
Authors: Galbraith R. A. , Kappas A.
Published: December 2017

Cobalt protoporphyrin (CoPP) in single subcutaneous doses produces prolonged weight loss in adult and aged male rats. The altered body weight level in treated animals is actively defended against starvation or overfeeding over prolonged time periods (greater than 50-100 days). The actions of CoPP on appetite and body weight regulation are biphasic, comprising an initial period of hypophagia, probably mediated centrally, until a particular body weight level is attained. Resumption of normal calorie intake follows, although lowered body weight levels are sustained, suggesting an additional action of the compound on peripheral substrate metabolism. Controlled decrements in body weight can be produced by repetitive low-dose CoPP treatment (e.g., 1 mumol/kg body wt weekly); low-dose regimens do not elicit altered hormonal homeostasis or aberrations in heme/cytochrome P-450 regulation that have been observed following larger doses (25-50 mumol/kg body wt) of the compound. CoPP may be a valuable probe with which to explore the role of heme-related molecules in the regulation of appetite and body weight.
Gene expression of tyrosine hydroxylase and neuropeptide Y in prevertebral ganglia of renal hypertensive rats
Authors: Krukoff T. L. , Zheng Y.
Published: December 2017

The gene expression of tyrosine hydroxylase (TH) and neuropeptide Y (NPY) was studied in prevertebral ganglia and adrenal glands of adult male rats during the development of renal hypertension (removal of 1 kidney/constriction of other kidney). Only tissues from rats with arterial pressures significantly elevated by day 3 were compared with those from controls. At 4 or 5 days after renal surgery, superior cervical ganglia, celiac-mesenteric plexus, adrenal glands, and stellate ganglia were surgically removed from nonfixed rats for Northern blot analysis or from perfusion-fixed rats for in situ hybridization. In all tissues, levels of TH mRNA were decreased in hypertensive rats; cells with decreased levels were scattered throughout each tissue. In contrast, levels of NPY mRNA were unchanged in hypertensive rats compared with controls. Changes in TH mRNA levels suggest that the developing phase of renal hypertension is associated with a decrease in sympathetic outflow to the periphery. In contrast, the failure of NPY mRNA levels to change suggests a different regulatory mechanism for NPY expression or a different role for NPY in sympathetic neurotransmission.
Intracellular pH rises and astrocytes swell after portacaval anastomosis in rats
Authors: Swain M. S. , Blei A. T. , Butterworth R. F. , Kraig R. P.
Published: December 2017

The basis for astrocytic swelling after the early period after portacaval anastomosis (PCA) is poorly defined. In other eukaryotic cells intracellular pH (pHi) and volume are determined, in part, by the same general mechanisms, yet how astrocytic pHi varies with enlargement of these cells after PCA is unknown. Therefore, direct measurements of pHi in astrocytes were made and compared with pericapillary astrocytic area as determined from electron micrographs in rats 5-8 days after PCA. Astrocytic area (n = 14 measurements for each group) was found to be significantly (P less than 0.0009) greater in PCA animals (n = 3) than in sham-operated control animals. (n = 3). Double-barrel pH-sensitive microelectrodes were used to measure pHi in neocortical cells defined by electrophysiological criteria to be astrocytic. Astrocytes (n = 25) from PCA animals (n = 5) had a resting membrane potential of 72 +/- 5 mV (mean +/- SD) and an pHi of 7.11 +/- 0.11 while comparable cells (n = 12) from sham-operated controls (n = 2) had a membrane potential of 81 +/- 6 mV and an pHi of 7.00 +/- 0.10. Astrocytes from PCA animals were significantly more depolarized (P less than 0.001) and alkaline (P less than 0.009), at a time when they were also significantly larger than those from sham-operated controls. Astrocytes are known to become more alkaline when they are activated by brief depolarizing stimuli. However, this is the first demonstration that such an interrelationship can also exist for steady-state conditions of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Increase in hepatic blood flow during early sepsis is due to increased portal blood flow
Authors: Wang P. , Ba Z. F. , Chaudry I. H.
Published: December 2017

Although hepatic blood flow increases significantly during early sepsis [as produced by cecal ligation and puncture (CLP)], it is not known whether this is due to the increase in portal or hepatic arterial blood flows. To study this, rats were subjected to CLP, after which they and sham-operated rats received either 3 or 6 ml normal saline/100 g body wt subcutaneously (i.e., all rats received crystalloid therapy). Blood flow in various organs was determined by using a radioactive microsphere technique at 5 and 20 h after CLP or sham operation. Portal blood flow was calculated as the sum of blood flows to the spleen, pancreas, gastrointestinal tract, and mesentery. Total hepatic blood flow was the sum of portal blood flow and hepatic arterial blood flow. A significant increase in portal blood flow and in total hepatic blood flow was observed at 5 h after CLP (i.e., early sepsis), and this was not altered by doubling the volume of crystalloid resuscitation after the induction of sepsis. In contrast, hepatic arterial blood flow during early sepsis was found to be similar to control; however, it was significantly reduced in late sepsis (i.e., 20 h after CLP). Cardiac output was significantly higher than the control in early sepsis. However, even in late sepsis, cardiac output and total hepatic blood flow were not significantly different from controls. These results indicate that the increased total hepatic blood flow during early hyperdynamic sepsis is solely due to the increased portal blood flow.
Glucose loading prevents freezing injury in rapidly cooled wood frogs
Authors: Costanzo J. P. , Lee R. E. , Wright M. F.
Published: December 2017

The wood frog (Rana sylvatica) is the most commonly studied of ten species of freeze-tolerant vertebrates. Under natural (i.e., slow) rates of cooling, freezing initiates the production of the cryoprotectant glucose, which is mobilized from the liver and distributed to tissues throughout the body. Rapid cooling during freezing is injurious to wood frogs, probably because cryoprotectant production and mobilization are inhibited. To test this hypothesis, we investigated whether rapid-cooling injury is reduced if exogenous glucose is experimentally introduced to tissues before freezing. Glucose-loaded and control (saline-injected) wood frogs were rapidly cooled during freezing to -2.5 degrees C and subsequently assayed for injury at both cellular (erythrocyte) and neuromuscular (behavioral reflex) levels. Rapid cooling produced substantial hemolysis in control frogs, but erythrocyte injury was significantly reduced in glucose-loaded frogs. Similarly neuromuscular injury was significantly higher in control frogs than in glucose-loaded frogs. These findings suggest that rapid-cooling injury results from an inadequate production and distribution of endogenous glucose during freezing. Furthermore, the inverse relationship between the degree of freezing injury and the quantity of exogenous glucose present strongly implicates glucose as a cryoprotectant in R. sylvatica.
Seasonal changes in hormone-sensitive and lipoprotein lipase mRNA concentrations in marmot white adipose tissue
Authors: Wilson B. E. , Deeb S. , Florant G. L.
Published: December 2017

White adipose tissue (WAT) and plasma samples were obtained from yellow-bellied marmots (Marmota flaviventris) throughout the year. Mean plasma triacylglycerol (TG), free fatty acids (FFAs), and glycerol were determined. There was a clear increase in FFAs and decrease in mean TG and glycerol during the hibernation period when animals were fasting, suggesting increased lipolysis. RNA was isolated from WAT biopsies at four times in the year: spring, summer, fall, and winter. There were significant changes in the relative levels of mRNA for lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) during the body mass cycle of the marmot. The relative levels of LPL mRNA are high during the mass gain phase of the year and that of HSL mRNA are high during the fasting period when endogenous lipid is utilized. These results suggest that the genes for LPL and HSL are regulated seasonally to control the adipose mass depot in marmots.
Cyanide excites medullary sympathoexcitatory neurons in rats
Authors: Sun M. K. , Jeske I. T. , Reis D. J.
Published: December 2017

Microinjections of cyanide (300 pmol) into the cardiovascular portion of the rostral ventrolateral reticular nucleus (RVL) of anesthetized rats (paralyzed and ventilated) produced a pressor response (26.5 +/- 1.6 mmHg, n = 7) and a transient depression of phrenic nerve discharge (90 +/- 8%, n = 5). Microiontophoretic applications of cyanide (less than or equal to 100 nA, 5-40 s) excited the RVL-spinal sympathoexcitatory neurons (31 out of 31). The response was dose dependent, reversible, independent of the baroreflex input to these neurons, and different from the responses of units with spontaneous discharge synchronized with the lung inflation or with unidentified function. The cyanide-induced excitation of the RVL-spinal sympathoexcitatory neurons was reversibly abolished by CO2+, applied iontophoretically at a dose at which the baroreflex inhibition of these neurons was not markedly affected whereas iontophoretic applications of kynurenic acid, a glutamate receptor antagonist, did not alter the response of the RVL-spinal sympathoexcitatory neurons to cyanide. It was concluded that cyanide induces a rapid Ca(2+)-dependent response of the RVL-spinal sympathoexcitatory neurons, which may underlie the cellular mechanism of these neurons in responding to ischemia-hypoxia.
Electrogenic H(+)-regulated sulfate-chloride exchange in lobster hepatopancreatic brush-border membrane vesicles
Authors: Cattey M. A. , Gerencser G. A. , Ahearn G. A.
Published: December 2017

Transport of [35S]sulfate by brush-border membrane vesicles (BBMV) of lobster (Homarus americanus) hepatopancreas was stimulated by an outwardly directed chloride gradient. In contrast, sulfate uptake was not enhanced by inwardly directed Na+ or K+ transmembrane gradients. An inside-positive membrane potential (valinomycin and K+) stimulated SO4(2-)-Cl- exchange, whereas an inside-negative membrane potential was inhibitory. Sulfate-sulfate exchange was not affected by alterations of transmembrane potential. An inwardly directed proton gradient, or the presence of low bilateral pH, enhanced SO4(2-)-Cl- exchange, but the H+ gradient alone did not stimulate sulfate uptake in chloride-equilibrated BBMV or in vesicles lacking internal Cl-. The stilbenes 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) strongly inhibited SO4(2-)-Cl- exchange. Sulfate influx occurred by a combination of carrier-mediated transfer, exhibiting Michaelis-Menten kinetics, and nonsaturable "apparent diffusion." 36Cl- influx into sulfate-loaded BBMV was stimulated by an inside-negative transmembrane potential compared with short-circuited vesicles. These results suggest that sulfate-chloride exchange in hepatopancreatic BBMV occurred by an electrogenic carrier mechanism exhibiting a 1:1 flux ratio that was modulated by internal and external H(+)-sensitive regulatory sites. The role of this antiport process in anion secretion is discussed.
Reversibility of load-induced changes in myosin heavy chain gene expression
Authors: Gupta M. , Zak R.
Published: December 2017

Changes in myosin expression were studied after the removal of functional overload of skeletal and cardiac muscles. In the first set of experiments the chicken slow tonic anterior latissimus dorsi muscle was overloaded by placing a lead band over the wing. In the overloaded muscles the normal developmental progression toward elimination of slow myosin SM-1 was accelerated. No reexpression of SM-1 took place after weight removal. In the second set of experiments rat heart was overloaded by constriction of abdominal aorta. Isomyosin composition and the abundance of mRNA coding for alpha- and beta-myosin heavy chain (MHC) was determined. The overload resulted in downregulation of the alpha-MHC with corresponding upregulation of beta-MHC expression. Debanding resulted in the regression of hypertrophy and rapid return of alpha-MHC to normal values. In contrast, the recovery in beta-MHC expression was much slower and at 7 wk of debanding still remained substantially elevated.
Adrenergic presynaptic antagonists and their mechanism of action in smooth muscle
Authors: Kalsner S.
Published: December 2017

The effects of veratridine and of yohimbine on the efflux of norepinephrine from guinea pig ureters was examined to gain insight into presynaptic receptor function. Ureter segments were stimulated at 1 and 2 Hz with 100 pulses in the absence and presence of yohimbine, veratridine, or the combination. Veratridine (4.5 or 6 x 10(-7) M) increased transmitter release. The enhancements of release by the adrenergic antagonist yohimbine and by veratridine were not additive, suggesting a common site of action. The lack of additivity was not linked to a ceiling effect since tetraethylammonium, which increases release by block of potassium channels, had an additive effect with veratridine. Protection experiments, done with veratridine as the protecting agent against phenoxybenzamine blockade, supported the interpretation that adrenergic antagonists and veratridine act at a common locus to enhance transmitter efflux. Although veratridine enhanced transmitter efflux like yohimbine, it only slightly reduced the inhibitory capacity of norepinephrine, confirming the likelihood of discrete sites of agonist and antagonist action. Veratridine and alpha-receptor antagonists might combine presynaptically with sites on the sodium channels of sympathetic nerve terminals to alter channel gating, namely the shifting of sodium channel activation to more negative potentials, and in this way increase the liberation of norepinephrine.
Subcellular enzyme binding and the regulation of glycolysis in anoxic turtle brain
Authors: Duncan J. A. , Storey K. B.
Published: December 2017

The association of glycolytic enzymes with the particulate fraction of the cell was assessed in the brain of the freshwater turtle, Pseudemys scripta elegans, using three different methodologies. Each method showed that a large percentage of each of eight enzymes was bound in brain. The effect of environmental anoxia (5 or 20 h submergence in N2-bubbled water at 7 degrees C) on the distribution of enzymes between free and bound states was analyzed. All three techniques showed a significant increase in the percentages of brain aldolase and glyceraldehyde-3-phosphate dehydrogenase bound during anoxia and no change in lactate dehydrogenase or creatine kinase binding. Two methodologies also showed an increase in the percent bound during anoxia for hexokinase, phosphofructokinase, and phosphoglycerate kinase. An increased association of glycolytic enzymes with structural elements of the cell during anoxia may physically position the glycolytic pathway to facilitate coupling between this ATP-generating pathway and ATP-utilizing processes, such as membrane ion pumps.
Renal nerves contribute to salt-induced hypertension in sinoaortic-denervated uninephrectomized rabbits
Authors: Ryuzaki M. , Suzuki H. , Kumagai K. , Kumagai H. , Ichikawa M. , Matsukawa S. , Matsumura Y. , Saruta T.
Published: December 2017

The objective of this study was to investigate the role of the renal nerves in the pathogenesis of salt-induced hypertension in sinoaortic-denervated uninephrectomized rabbits. Twelve rabbits were divided into two groups. Sinoaortic-denervated uninephrectomized rabbits with intact renal nerves (sham group: n = 6) and without renal nerves (RDN group; n = 6). In both groups, 2 days of 154 meq/l NaCl loading was followed by 10 days of 1,700 meq/l NaCl loading. We administered 154 meq/l or 1,700 meq/l NaCl intravenously at every 8 h. Serial changes in mean arterial pressure (MAP) and heart rate (HR) were recorded using a microcomputer system. We chronologically measured hematocrit, serum osmolality, serum sodium, potassium, and chloride concentration, serum creatinine, plasma renin activity, plasma aldosterone, plasma norepinephrine, plasma arginine vasopressin, and plasma atrial natriuretic peptide. Urine volume and body weight were recorded every day, as were urinary concentrations of sodium, potassium, and chloride. The basal value of MAP in the sham group was significantly higher than that in the RDN group (on day -2, 111 +/- 1 mmHg for sham, 99 +/- 2 for RDN, P less than 0.001). Hypertonic saline loading induced an elevation of blood pressure in the sham group (126 +/- 2 mmHg on day 4, 127 +/- 2 on day 7, 124 +/- 4 on day 10). There were no significant changes in the response to salt loading in the RDN group. In the sham group, the retention of sodium was significant compared with that in the RDN group on day 5, and this difference was maintained until the end of the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
Fluid-regulating hormones during exercise when central blood volume is increased by water immersion
Authors: Sheldahl L. M. , Tristani F. E. , Connelly T. P. , Levandoski S. G. , Skelton M. M. , Cowley A. W.
Published: December 2017

To examine the influence of an increase in central blood volume with head-out water immersion (WI) on fluid-regulating hormones during exercise, 10 healthy men underwent upright leg cycle exercise on land and with WI. Venous plasma renin activity and plasma venous concentrations of atrial natriuretic peptide, plasma aldosterone, and arginine vasopressin were determined at exercise intensities corresponding to approximately 40, 60, 80, and 100% peak oxygen consumption (VO2) and at minutes 1 and 5 of seated rest recovery within each environment. Peak VO2 did not differ on land and with WI. Atrial natriuretic peptide concentration was higher (P less than 0.05) and plasma renin activity was lower (P less than 0.05) in water than on land at 40% peak VO2 through minute 5 of recovery. Plasma aldosterone and arginine vasopressin concentrations were lower (P less than 0.05) in water at peak exercise and at minutes 1 and 5 of recovery. Osmolality and plasma sodium and potassium concentrations during exercise were similar in water and on land. The results indicate that WI alters the circulating levels of several hormones involved in fluid and electrolyte regulation during exercise. These hormonal alterations can best be explained by stimulation of low-pressure baroreceptors and atrial stretch due to increased central blood volume with head-out WI.
Regulation of calbindin mRNA and calbindin turnover in intestine and shell gland of the chicken
Authors: Bar A. , Striem S. , Vax E. , Talpaz H. , Hurwitz S.
Published: December 2017

A synthetic oligonucleotide was used as a probe for measurement of calbindin mRNA in the shell gland and intestine of chickens. The half time of calbindin mRNA in the duodenum and shell gland was estimated at 2 and 3.6 h and that of calbindin at 13.9 and 32.6 h, respectively. The formation rates of calbindin mRNA were 0.37 and 0.17 pmol.h-1.g-1 and the rate of calbindin formation was 0.099 and 0.031 microgram.pmol mRNA-1.h-1 in the duodenum and shell gland, respectively. In the shell gland, calbindin mRNA and calbindin appeared at the time of sexual maturation during calcification of the first egg shell. Calbindin mRNA fluctuated markedly during the daily egg cycle, in close temporal association with egg shell calcification. When Ca2+ deposition was eliminated by expulsion of the ovum, the rise in calbindin mRNA was prevented. An indirect suppression of Ca2+ deposition by administration of the carbonic anhydrase inhibitor acetazolamide also resulted in a decrease in calbindin mRNA. The results are consistent with a possible role of Ca2+ flux in the regulation of calbindin mRNA appearance in the shell gland of chickens.
Intermittent exercise alters endurance in an eight-legged ectotherm
Authors: Weinstein R. B. , Full R. J.
Published: December 2017

Most animals move intermittently, yet many proposed performance limitations of terrestrial locomotion are based on steady-state measurements and assumptions. We examined the effect of work-rest transitions by exercising the ghost crab, Ocypode quadrata (28.1 +/- 8.1 g), intermittently on a treadmill at 0.30 m/s, a supramaximal speed [i.e., greater than the speed that elicits the maximal rate of oxygen consumption (VO2)]. Duration of the exercise and pause periods, ratio of exercise to pause, and speed during the exercise period were varied to determine the effect on performance. Crabs fatigued after 7.5 min of continuous running, a distance capacity (i.e., total distance traveled before fatigue) of 135 m. When the task was done intermittently with 2-min exercise and 2-min pause periods, the crabs fatigued after 87 min (a total distance of 787 m), representing an 5.8-fold increase in distance capacity compared with continuous exercise at the same absolute speed (0.30 m/s) and a 2.2-fold increase in distance capacity compared with continuous exercise at the same average speed (0.15 m/s). Pause periods less than 30 s did not result in greater distance capacity compared with continuous exercise at the same average speed. Longer (3-5 min) and shorter exercise periods (less than or equal to 30 s) decreased distance capacity. Leg muscle lactate increased 10-fold to 15 mumol/g leg during intermittent exercise. However, significant amounts of lactate were cleared from the leg during the brief pause periods.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal blood flow varies during normal activity in conscious unrestrained rats
Authors: Grady H. C. , Bullivant E. M.
Published: December 2017

The extent to which renal blood flow (RBF) varied during normal daily activity and its dependence on renal nerve activity were studied in unrestrained rats. RBF (measured with a pulsed Doppler flow probe) and behavior pattern (observed with a video camera) were recorded during both phases of the light-dark cycle (n = 11). RBF was highest (100%) when the rat was fully relaxed and apparently asleep (9% time) but was significantly lower (P less than 0.01) during the remainder of the time. When quiescent but not fully relaxed, RBF was 89.7 +/- 0.3% of the maximum; when alert and completely still, it was 74.1 +/- 0.8%; and when grooming, it was 63.7 +/- 0.9%. Mean daily RBF was 80% of maximum flow. During saline infusion into cuffs around the renal arteries, RBF was reduced to 38.4 +/- 0.7% of maximum flow by gentle handling. When the infusion was changed to Xylocaine (5%), which blocked transmission in the renal nerve, similar treatment reduced RBF to 80.2 +/- 0.7% with ipsilateral and to 94.7 +/- 0.7% with bilateral infusions. We conclude that RBF varies considerably in unrestrained animals under normal conditions and that the variations largely result from changes in renal nerve activity.
Mifepristone (RU 486), a blocker of type II glucocorticoid and progestin receptors, reverses a dietary form of obesity
Authors: Okada S. , York D. A. , Bray G. A.
Published: December 2017

The effect of mifepristone (RU 486), a blocker of type II glucocorticoid receptors on the development of obesity that follows the feeding of a high-fat (HF) diet to Osborne-Mendel (OM) rats, has been investigated. OM rats fed a HF diet gained more weight and had larger retroperitoneal and parametrial fat pads than OM rats fed a high-carbohydrate low-fat (LF) diet. RU 486 (30 mg.kg-1.day-1) for 14 days completely reversed the body weight gain and the increase in fat pad size of OM rats fed a HF diet. RU 486 had no effect on body weight of OM rats fed a LF diet, but did reduce fat pad weights. The data suggest that type II glucocorticoid receptor activity modulates body fat deposition and is essential for the development of obesity, although a minor role for progestin receptor activity cannot be ruled out.
Effects of intravenous saline infusion on fetal ovine lung liquid secretion
Authors: Davis T. A. , Gause G. , Perks A. M. , Cassin S.
Published: December 2017

These studies were designed to investigate the relationship between body fluid volume expansion and secretion of lung liquid in fetal sheep. Twelve fetal animals were used for saline infusion studies after providing them with indwelling vascular catheters and an exteriorized tracheal loop. An additional 10 animals were used as controls. Lung liquid production was measured using an impermeant tracer technique (Blue Dye Dextran). Saline infusion at 1.6, 4.0, 15.6, and 19.2 ml.kg-1.h-1 did not alter significantly lung liquid secretion rates. These results demonstrate that 1) intravenous infusion of saline at relatively high rates in the ovine fetus does not affect net fetal lung liquid formation rate, and 2) the lungs of chronically catheterized, unanesthetized fetal sheep probably do not participate in regulation of excess fluid and electrolytes.
Models of neurohypophyseal homeostasis
Authors: Fitzsimmons M. D. , Roberts M. M. , Sherman T. G. , Robinson A. G.
Published: December 2017

Rats subject to prolonged (3-6 days) hypernatremia show significantly decreased pituitary vasopressin content as well as increased levels of hypothalamic vasopressin mRNA; these values return to baseline levels after the stimulus is removed. In this paper, we tested whether a single cellular mechanism for regulation of synthesis could account for the experimental observations of both pituitary hormone depletion-repletion and hypothalamic mRNA content. We developed several “minimal” models of vasopressin synthesis in which control of hormone synthesis was regulated exclusively by transcription, translation, or mRNA decay and tested each model to see which best emulated the dynamics of neuro-hypophyseal vasopressin content and hypothalamic vasopressin mRNA. Experimental data provided parameters for pituitary content, baseline and stimulated release rates, mRNA decay, transcription, and translation. Models based exclusively on translation and mRNA decay failed to produce predictions similar to experimental observations. Of the models tested, the transcription model provided predictions most consistent with laboratory data, although some quantitative differences remain. The results of the computer modeling strongly suggest that transcription represents the predominant means by which magnocellular neurons regulate vasopressin synthesis.
Verapamil prevents insulin antinatriuresis in euglycemic rats
Authors: Gupta A. K. , Clark R. , Kirchner K. A.
Published: December 2017

To determine whether calcium entry is necessary for insulin antinatriuresis, urinary sodium excretion was determined before and during euglycemic insulin administration in rats receiving verapamil (10 micrograms.kg-1.min-1) or vehicle. In vehicle rats, insulin reduced sodium excretion from 2.7 +/- 0.5 to 0.98 +/- 0.2 mu eq/min (P less than 0.05) without altering arterial pressure or inulin clearance. Insulin did not reduce sodium excretion in rats receiving verapamil. Baseline mean arterial pressure was lower in verapamil rats than in vehicle rats. To exclude the possibility that lower baseline arterial pressures prevented insulin antinatriuresis, insulin's effect on sodium excretion was determined in rats receiving captopril at a dose that reduced arterial pressure to the level observed in verapamil rats, and in verapamil rats with angiotensin II levels fixed to maintain arterial pressure equivalent to vehicle rats. In captopril rats, insulin reduced (P less than 0.05) sodium excretion from 1.07 +/- 0.3 to 0.3 +/- 0.01 mu eq/min, even though arterial pressure was not different from that in verapamil rats. Insulin failed to reduce sodium excretion in verapamil rats receiving angiotensin II. Thus verapamil prevents insulin antinatriuresis by renal mechanisms related to inhibition of calcium entry. Additionally, insulin antinatriuresis is independent of angiotensin II.
Human placental vitamin B6 (pyridoxal) transport: normal characteristics and effects of ethanol
Authors: Schenker S. , Johnson R. F. , Mahuren J. D. , Henderson G. I. , Coburn S. P.
Published: December 2017

The aims of this study were to define normal human placental transport of pyridoxal, an important form of vitamin B6 in pregnancy, and to determine the effect of short-term alcohol on this process. Our studies used the isolated single cotyledon from the term placenta. Pyridoxal crossed the human placenta readily in both directions, but the transfer was a little less than half that of antipyrine and was significantly greater in the direction of the fetus. Pyridoxine appeared to have a similar clearance from the maternal compartment as pyridoxal, but transport of intact pyridoxal 5'-phosphate was much smaller. There was no saturable transfer of pyridoxal, and it was not transferred from the maternal to fetal compartments against a concentration gradient. Placental concentration of pyridoxal exceeded both maternal and fetal perfusate pyridoxal concentrations, but this concentration was equal for both perfusion directions. These composite data are most suggestive of passive transport of pyridoxal across the placenta, binding of the vitamin in the placenta as an explanation for its concentration there, and greater phosphorylation of pyridoxal in the placenta when the compound is transferred in the fetal direction, possibly displacing pyridoxal from its binding sites and permitting its greater release into the fetal compartment. Alcohol, 400-250 mg/dl over 2.5 h, inhibited the transport of pyridoxal from the maternal to fetal compartments by approximately 42% (P = 0.03) and resulted in a lower transfer of pyridoxal 5'-phosphate into the fetal perfusate (P = 0.02).
Renal nerve activity in rats with spontaneous hypertension: effect of converting enzyme inhibitor
Authors: Kumagai H. , Averill D. B. , Ferrario C. M.
Published: December 2017

We studied the effects of chronic oral inhibition of angiotensin-converting enzyme on the baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) in 14-wk-old conscious spontaneously hypertensive rats (SHR; n = 12) and age-matched Wistar-Kyoto rats (WKY; n = 11). Rats were treated with lisinopril (10 mg.kg-1.day-1 in tap water) or vehicle for 7 days. We evaluated the baroreflex control of efferent RSNA and HR in awake rats 2 days after implantation of electrodes around the renal sympathetic nerves. The relation between mean arterial pressure (MAP) and either RSNA or HR was analyzed by a logistic function curve during intravenous infusions of phenylephrine and nitroglycerin. The maximum gain of the curve was considered as the sensitivity of the baroreflex. MAP in lisinopril-treated SHR averaged 93 +/- 3 mmHg, a value lower than that obtained in vehicle-treated SHR (147 +/- 5 mmHg) but not in WKY (96 +/- 4 mmHg). In vehicle-treated SHR baroreflex sensitivity (-4.3 +/- 0.5% change nerve activity/mmHg) was significantly (P less than 0.005) smaller than that of WKY (-15.8 +/- 1.5%/mmHg). Seven days of oral treatment of lisinopril caused significant improvement of the baroreflex sensitivity in SHR (-10.5 +/- 0.7%/mmHg, P less than 0.01). The maximum gain of MAP and HR relation of lisinopril-treated SHR was also larger (P less than 0.05) than that of vehicle-treated SHR.(ABSTRACT TRUNCATED AT 250 WORDS)