bluuebunny/crossref_metadata_2025 huggingface dataset:
Is superoxide demonstration by electron-spin resonance spectroscopy really superoxide?
Authors: Nakazawa H. , Ichimori K. , Shinozaki Y. , Okino H. , Hori S.
Published: December 2017

A recent study has indicated that the generation of an oxygen radical in freeze-clamped myocardium on reperfusion can be directly demonstrated using electron-spin resonance spectroscopy (ESR). However, the results need to be analyzed with caution, since artifactual radicals are misleading problems common to this method. To test whether that reported superoxide is truly the biologically existing radical or an artifactual radical, we performed experiments using isolated, perfused rat and rabbit hearts and open-chest canine hearts subjected to ischemia/reperfusion. Radicals were freeze trapped at 77 degrees K, and ESR measurements were made. The ESR spectra exhibited four free radicals. Among these, two radicals which had been previously claimed as superoxide and a nitrogen-centered radical were shown as mechanically yielded artifactual radicals. These were produced by pulverization of the frozen sample. In artifact-free samples, superoxide could not be detected. The radicals native to the myocardium were identified as coenzyme Q10-. and another radical the species of which remains unclear.
Ionic basis of depressed automaticity and conduction by acetylcholine in rabbit AV node
Authors: Nishimura M. , Habuchi Y. , Hiromasa S. , Watanabe Y.
Published: December 2017

To investigate the ionic mechanisms underlying the negative chrono- and dromotropic effects of acetylcholine (ACh) on the atrioventricular (AV) node, experiments were carried out in rabbit AV node preparations with the use of double-microelectrode techniques. In current-clamp experiments (n = 6), 10(-6) M ACh hyperpolarized the resting membrane from -42.3 to -58.2 mV, decreased the specific membrane resistance from 2.54 to 1.27 k omega.cm2, decreased the space constant from 556 to 384 microns, and reduced the membrane time constant from 23.0 to 12.4 ms. Under voltage-clamp conditions, 10(-6) M ACh decreased the slow inward current by 11% and activated an ACh-sensitive outward K+ current (IACh). IACh possessed an inward rectifying property and exhibited a relaxation phenomenon with a time constant of 60-100 ms at a membrane potential of 0 to -80 mV. Its reversal potential varied with a slope factor of 56 mV per 10-fold increase in external K+ concentration. These results suggest that 1) IACh is selective for K+, 2) IACh inhibits phase 4 and phase 0 depolarizations and reduces the space constant for electronic current spread in the AV node, and 3) the negative chrono- and dromotropic actions caused by IACh may be augmented by the ACh-induced reduction in the slow inward current.
Quantification of regional myocardial dysfunction after acute ischemic injury
Authors: Glower D. D. , Spratt J. A. , Kabas J. S. , Davis J. W. , Rankin J. S.
Published: December 2017

Quantification of myocardial performance after regional ischemic injury is difficult because available performance indexes are markedly dependent on concurrent load changes. To develop a more load-insensitive index of myocardial function during ischemia, eight conscious dogs were instrumented to measure left ventricular pressure with micromanometers and myocardial segment length with ultrasonic dimension transducers. Preload was varied by transient vena caval occlusion during control conditions, after 15 min of coronary occlusion, and at intervals during 24 h of reperfusion. Acute ischemia shifted the linear relationship between segmental stroke work (SW) and end-diastolic segment length (EDL) rightward, diminishing the slope and increasing the chi-intercept. Preload recruitable work area (PRWA), defined as the area under the SW-EDL curve, reflected changes in both slope and intercept. During acute ischemia, conventional performance indexes and PRWA decreased significantly and required up to 24 h of reperfusion to return to control values. Of all parameters examined, PRWA was most responsive to prolonged ischemic dysfunction after reperfusion and was insensitive to concurrent load changes. Thus PRWA provides improved precision in quantifying of myocardial dysfunction after regional ischemic injury. This parameter should be especially useful in assessing the subtle effects of acute interventions designed to modify functional recovery.
THE IMPORTANCE OF EXOGENOUS FAT IN FATTY INFILTRATION OF THE LIVER OF DOGS
Authors: Li Tsan-Wen , Freeman Smith
Published: December 2017

Volume 145, page 667: The Importance of Exogenous Fat in Fatty Infiltration of the Liver of Dogs, by Tsan-wen Li and Smith Freeman.

In paragraph 2 under Summary (p. 674) the word increase should read "decrease".
Measurements on the Elasticity of the Isolated Rat Lung
Authors: Lawton Richard W. , Joslin Doyle
Published: December 2017

Page 117. Richard W. Lawton and Doyle Joslin, "Measurements on the Elasticity of the Isolated Rat Lung." Lines 11 to 7 from bottom of page, figure 7, and reference (12). Add the following statement: "At the end of a normal expiration the total lung volume is of the order of 5 cc. (12) or equivalent to the calculated V0 in this case. Tidal air should lie, therefore, between 0 and 1.0 to 1.5 cc. on the ordinate."
Pioglitazone attenuates hypertension and inhibits growth of renal arteriolar smooth muscle in rats
Authors: Dubey R. K. , Zhang H. Y. , Reddy S. R. , Boegehold M. A. , Kotchen T. A.
Published: December 2017

Hypertension is frequently associated with insulin resistance. We evaluated the effects of pioglitazone, an agent that increases insulin sensitivity, on the development of hypertension in the Dahl salt-sensitive (Dahl-S) rat and in the one-kidney, one-clip Sprague-Dawley rat. We also evaluated the effects of pioglitazone on growth of cultured preglomerular renal arteriolar smooth muscle cells. In Dahl-S rats fed a 3% NaCl diet, tail systolic blood pressures and direct arterial pressures were lower (P < 0.05) in pioglitazone-treated (20 mg/kg daily by gavage for 3 wk) than in control rats (n = 10 rats/group). In one-kidney, one-clip Sprague-Dawley rats, systolic blood pressures were also lower in pioglitazone-treated animals (P < 0.0001). In vitro, proliferation of arteriolar smooth muscle cells was stimulated (P < 0.01) by insulin, epidermal growth factor (EGF), and fetal calf serum (FCS); pioglitazone (5 microM) reversibly inhibited (P < 0.01) insulin-, EGF-, and FCS-induced proliferation. Pioglitazone (0.01-100 microM) also inhibited insulin- (1 mU/ml), EGF- (100 ng/ml), and 5% FCS-induced [3H]thymidine incorporation in a concentration-dependent manner (P < 0.01). Thus pioglitazone attenuated the development of hypertension in the Dahl-S rat and the one-kidney, one-clip rat. The ability of pioglitazone to inhibit growth of vascular smooth muscle may contribute to its hypotensive effect.
Interleukin-8 modulates feeding by direct action in the central nervous system
Authors: Plata-Salaman C. R. , Borkoski J. P.
Published: December 2017

Interleukin-8 (IL-8) is released in response to infection, inflammation, and trauma. The most important stimuli for IL-8 release during these pathological processes are IL-1, tumor necrosis factor, and bacterial lipopolysaccharide (endotoxin), factors that have been shown to suppress feeding. In the present study, the participation of IL-8 on the central regulation of feeding was investigated. Intracerebroventricular (icv) microinfusion of recombinant human IL-8 (rhIL-8, 1.0-100 ng/rat) suppressed the short-term (2-h) food intake. The most effective dose of rhIL-8, 20 ng, decreased 2-h food intake by 25% and nighttime food intake by 23%. Intracerebroventricular microinfusion of anti-rhIL-8 antibody (200 and 500 ng) blocked the effect of 20 ng rhIL-8 on 2-h and nighttime food intakes. Computerized analysis of behavioral patterns for the 2-h period demonstrated a specific reduction of meal size (by 33%), whereas meal frequency and meal duration were not affected after the icv microinfusion of 20 ng rhIL-8. This short-term food intake suppression by icv rhIL-8 was accompanied by a small, but significant, increase in cerebrospinal fluid-brain and rectal temperatures. Intraperitoneal administration of rhIL-8 in doses equivalent to those administered centrally had no effect on food intake. The results suggest that IL-8 acts directly in the central nervous system to decrease feeding. This effect of IL-8 may contribute to the food intake suppression frequently accompanying pathological processes.
Alterations in brain hexokinase activity associated with heart failure in rats
Authors: Patel K. P. , Zhang P. L. , Krukoff T. L.
Published: December 2017

This study examined the activity of discrete regions of the brain as assessed with histological localization and photodensitometric quantification of the metabolic enzyme hexokinase in a group of rats with coronary occlusion (HF) and in sham-operated control rats. Three weeks after surgery, the mean left ventricular end diastolic pressure and right atrial pressure were elevated, and left ventricular peak systolic pressure was decreased in the HF group compared with the sham group; these findings are also observed during heart failure. In addition, histological data indicated that there was a 37.6 +/- 2.8% outer and 40.8 +/- 3.1% inner infarct of the myocardium in the group of rats with HF (n = 6). Rats in the control group had no observable damage to the myocardium (n = 6). Accompanying these symptoms of heart failure were significant increases in hexokinase activity in the parvocellular (pPVN, 16.3%) and magnocellular (mPVN, 17.6%) divisions of the paraventricular nucleus of the hypothalamus, and in the locus ceruleus (LC, 17.1%). No changes in hexokinase activity were observed in the median preoptic area, supraoptic nucleus (SON), subfornical organ, or posterior hypothalamus. These results reinforce the idea that heart failure (with coronary occlusion) is associated with changes in specific areas in the brain and that metabolic alterations in the pPVN, mPVN, and LC are likely related to alterations in vasopressin production, blood volume regulation, and sympathoexcitation observed in the heart failure state.
Genetic development of an inbred rat strain with increased resistance adaptation to a hot environment
Authors: Furuyama F. , Ohara K.
Published: December 2017

The purpose of this study was to demonstrate resistance adaptation based on genotypic adaptation and to develop an inbred rat strain with genotypic resistance adaptation to a hot environment. Survival time (ST) at an ambient temperature (Ta) of 42.5 degrees C was determined without appreciable thermal damage. Rats with the longest ST were sibmated over 30 generations and designated FOK. The ST, evaporative water loss, and body water economy increased rapidly during the first 10-15 generations, followed by a more gradual increase. The FOK rat resisted a Ta of 42.5 degrees C for > 5 h; this ability was hereditary. Body size progressively decreased during the early generations. The ST was longer (P < 0.01) and evaporative water loss was significantly higher (P < 0.01) in the FOK rat compared with three other strains. Tail lengths in the FOK rat were slightly shorter than those of three controls (P < 0.01). The heat loss system in the FOK rat may depend on the ability to mobilize and evaporate body fluids efficiently. FOK rats can be used for phenotypic comparisons with other strains, as well as in molecular genetic studies on thermoregulation, osmoregulation, and resistance adaptation to heat using recombinant inbred and recombinant congenic lines.
Role of the brain stem in generating the 2- to 6-Hz oscillation in sympathetic nerve discharge
Authors: Zhong S. , Huang Z. S. , Gebber G. L. , Barman S. M.
Published: December 2017

We tested the hypothesis that brain stem circuits normally generate a 2- to 6-Hz oscillation in sympathetic nerve discharge (SND). Experiments were performed on baroreceptor-denervated decerebrate cats and urethan-anesthetized rats in which renal or splanchnic SND was recorded along with field potentials (population activity) from sites in the rostral ventrolateral medulla, medullary raphe, or medullary lateral tegmental field. Our major findings were as follows. 1) Population activity recorded from the three medullary regions contained a 2- to 6-Hz oscillation. 2) The 2- to 6-Hz oscillation in population activity recorded from some medullary sites was correlated to that in SND. Peak coherence in the 2- to 6-Hz band approached a value of 1 in some cases. 3) Whereas cervical spinal cord transection abolished or markedly reduced SND, the 2- to 6-Hz oscillation in medullary activity was essentially unchanged. These results support the view that the 2- to 6-Hz oscillation in SND can be generated in the brain stem of cats and rats.
Current-noise analysis of Na absorption in the embryonic coprodeum: stimulation by aldosterone and thyroxine
Authors: Clauss W. , Hoffmann B. , Krattenmacher R. , Van Driessche W.
Published: December 2017

The mechanism and regulation of sodium transport in the embryonic coprodeum of chicken were investigated with isolated epithelia in vitro by electrophysiological techniques. Electrogenic sodium transport (INa) was measured in Ussing chambers by the short-circuit current (Isc) technique and identified by the diuretic amiloride or by removal of sodium from the apical medium. Apical sodium channels and the kinetics of amiloride binding were investigated by current-noise analysis. Isc and INa were measured under control conditions and under the influence of in vitro incubation with aldosterone and thyroxine. At 20 days the embryonic coprodeum has an Isc of 12.6 +/- 1.4 microA/cm2 and a transepithelial resistance of 519 +/- 40 omega.cm2. Amiloride blocks 9.0 +/- 1.3 microA/cm2 of the Isc, which represents electrogenic Na+ absorption and can be inhibited by serosal ouabain. Aldosterone does not stimulate Isc or INa, whereas thyroxine increases Isc and INa about threefold. Aldosterone in combination with thyroxine increases Isc and INa further to about five- to sixfold. In both cases the hormonal stimulation can be totally blocked by spironolactone. Current-noise analysis of the apical Na+ entry step reveals amiloride-sensitive Na+ channels with a single-channel current of approximately 2.3 pA and a channel density of 9-16 million/cm2 under stimulated conditions. Half-maximal amiloride block occurs at 0.8-1 microM. The hormones stimulate Na+ absorption by increasing the Na+ channel density and not the single-channel current.(ABSTRACT TRUNCATED AT 250 WORDS)
Glucosidic pathways of glycogen breakdown and glucose production by muscle from postexercised frogs
Authors: Fournier P. A. , Guderley H.
Published: December 2017

Muscle and body glucose in frogs increases markedly during the initial hour of recovery after strenuous exercise. The liver is not the major source responsible for this accumulation. This is indicated by the stability of liver glycogen levels after exercise and by the observation that hepatectomized and normal frogs accumulate similar amounts of glucose in their muscles and body during recovery. The renal contribution cannot account for this increase in body glucose. Most of the glucose that accumulates in the body after exercise has a muscular origin, as indicated by the facts that two-thirds of the body glucose is found in muscle and that the intracellular levels of muscle glucose are much higher than those of the plasma. The glucose that accumulates outside muscle may also have a muscular origin. The glucosidic pathways of glycogen breakdown are the only metabolic avenue with sufficient capacity to account for the amount of glucose accumulated in muscle during the first hour of recovery. These results indicate that the ability of an isolated preparation of frog muscle to liberate glucose during recovery from exercise (Fournier et al. J. Biol. Chem. 267: 8234-8238, 1992) is not an artifactual metabolic curiosity but rather a metabolic reality that takes place in vivo. Glucose accumulation during recovery is thought to facilitate the metabolic transition of frog carbohydrate metabolism from a catabolic state, characteristic of exercise, to an anabolic one.
Lateral parabrachial subnucleus lesions abolish feeding induced by mercaptoacetate but not by 2-deoxy-D-glucose
Authors: Calingasan N. Y. , Ritter S.
Published: December 2017

Lesions of the area postrema/nucleus of the solitary tract (AP/NTS) region abolish feeding induced by mercaptoacetate (MA) and 2-deoxy-D-glucose (2DG), metabolic inhibitors that selectively impair fatty acid and glucose utilization, respectively. Because the AP/NTS region is important for both MA- and 2DG-induced feeding, the present experiment investigated the involvement of the lateral parabrachial nucleus (1PBN), which is innervated by AP/NTS neurons, in these feeding responses. Electrolytic and ibotenic acid lesions were directed at the entire parabrachial nucleus or at specific lateral parabrachial subnuclei. Rats with electrolytic lesions were tested for feeding in response to 0.9% NaCl (subcutaneous or intraperitoneal), MA (400, 600, and 800 mumol/kg ip), and 2DG (100 and 200 mg/kg sc). Ibotenate-lesioned rats were tested with NaCl and MA only. Lesions were verified either by cresyl violet staining or by glial fibrillary acidic protein immunohistochemistry. Bilateral destruction of the 1PBN severely impaired or abolished MA-induced feeding. Cell bodies important for MA-induced feeding appear to be localized in the dorsal-central 1PBN subnuclear area, because both electrolytic and cytotoxin microlesions centered in this area abolished feeding in response to MA. Fibers of passage important for MA-induced feeding appear to pass through the external and superior 1PBN because electrolytic but not cytotoxin lesions of these subnuclei disrupted the feeding response. In contrast, 2DG-induced feeding did not differ significantly from sham-lesioned controls in any of the 1PBN lesion groups. These results indicate that 2DG and MA stimulate feeding by activating separate central neural pathways and, perhaps, distinct metabolic controls of food intake.
Local administration of EAA antagonists blocks light-induced phase shifts and c-fos expression in hamster SCN
Authors: Rea M. A. , Buckley B. , Lutton L. M.
Published: December 2017

Syrian hamsters were fitted with guide cannulas stereotaxically aimed at the suprachiasmatic nuclei (SCN) and housed in constant darkness in cages equipped with running wheels. Animals received 300-nl injections of either vehicle, CNQX, or MK-801 into the region of the SCN 5 min before a brief (10 min at 20 lx) light exposure. Local administration of either 1 mM CNQX or 1 mM MK-801 at circadian time (CT) 18 significantly inhibited light-induced phase advances (vehicle = 52 +/- 9 min; CNQX = 12 +/- 7 min; MK-801 = 12 +/- 5 min; P < 0.05 relative to vehicle+light group). The effects of both drugs were reversible and dose related. Injection of 1 mM MK-801 at CT13.5 resulted in a 71% inhibition of light-induced phase delays (vehicle = -51 +/- 6 min; MK-801 = -15 +/- 5 min; P < 0.05), while CNQX failed to significantly inhibit light-induced phase delays (-39 +/- 10 min). Local administration of either 1 mM CNQX or MK-801 into the SCN region reduced the number of Fos-immunoreactive cells relative to vehicle-injected controls by approximately 32 and 44%, respectively (vehicle = 951 +/- 79; CNQX = 643 +/- 135, P < 0.05; MK-801 = 533 +/- 143, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Modified microdialysis probe for sampling extracellular fluid and administering drugs in vivo
Authors: Yadid G. , Pacak K. , Kopin I. J. , Goldstein D. S.
Published: December 2017

In vivo microdialysis provides an important new tool for investigating changes in extracellular fluid levels of endogenous compounds in vivo. Delivery of drugs via the microdialysis probe can be used to study local release and metabolism of neurotransmitters, but the dialysis membrane limits diffusion of substances between the perfusate and the extracellular fluid. Thus there may be considerable delay in responses, drug concentrations at the effector sites are less than those in the probe, and high-molecular-weight substances cannot traverse the membrane at all. This report describes a simple modification of commercially available microdialysis probes. A cannula is glued to the external surface of the probe. When glycine was administered via the cannula into the striatum of conscious rats, increments in microdialysate concentrations of dopamine were at least 10 times greater than when glycine was administered via the dialysis fluid in the probe. The threshold glycine dose for behavioral (turning) effects was also decreased by approximately 60-fold, and the time to the peak neurochemical and behavioral effects was markedly decreased. The modified probe did not destroy local catecholaminergic cells, as indicated by tyrosine hydroxylase immunofluorescence. Use of the modified microdialysis probe should facilitate pharmacological and neuroendocrine studies in behaving animals.
Influence of the renal medullary circulation on the control of sodium excretion
Authors: Roman R. J. , Zou A. P.
Published: December 2017

Although the role of the renal medullary circulation in the control of urinary concentrating ability is well established, its potential influence on tubular sodium reabsorption is not generally recognized. Nearly 30 years ago, changes in the intrarenal distribution of blood flow were first proposed to contribute to the natriuretic response to volume expansion. However, the lack of reliable methods for studying medullary blood flow limited progress in this area. The recent development of laser-Doppler flowmetry and videomicroscopic techniques for the study of the vasa recta circulation has renewed interest in the role of medullary hemodynamics in the control of sodium reabsorption. Results of these studies indicate that changes in renal medullary hemodynamics alter renal interstitial pressure and the medullary solute gradient and play an important role in the natriuretic response to elevations in renal perfusion pressure, intravenous infusion of saline, and changes in tubular sodium reabsorption produced by vasoactive compounds. What is emerging from these studies is the view that changes in renal medullary hemodynamics represent an important but misunderstood and long-ignored factor in the control of tubular sodium reabsorption.
Impairment of osmotically stimulated AVP release in patients with primary polydipsia
Authors: Moses A. M. , Clayton B.
Published: December 2017

The secretion of arginine vasopressin (AVP) from the posterior pituitary is primarily and finely regulated by the osmolality of plasma. Even though a number of factors alter osmolality-induced release of AVP, there are no published data in humans that have addressed the role of chronic overhydration on this phenomenon. To address this problem we have identified eight patients with primary polydipsia using criteria not involving measurement of AVP, and have subjected them to standardized infusions of hypertonic saline. These patients had less AVP in both plasma and urine in relation to plasma osmolality than was found in normal subjects. In addition, their rate of rise of plasma and urine AVP was less than in normal subjects. Their osmotic threshold for AVP release may have been higher than normal. These data demonstrate that chronic overhydration in humans downregulates the release of AVP in response to hypertonicity. This phenomenon may explain the impairment of urine concentration in patients with primary polydipsia and emphasizes the basis of the difficulty that may occur clinically in differentiating between patients with primary polydipsia and partial central diabetes insipidus.
Basic fibroblast growth factor may mediate proliferation in the compensatory adrenal growth response
Authors: Basile D. P. , Holzwarth M. A.
Published: December 2017

We have investigated the role of basic fibroblast growth factor (bFGF) in the neurally mediated compensatory adrenal growth response. Unilateral adrenalectomy resulted in a 13, 6, and 22% increase in adrenal weight, protein, and DNA content, respectively, and 33-40% increases in the rate of cell proliferation measured by [3H]thymidine incorporation in vitro. Three forms of bFGF, approximately 18.6, 21, and 22.5 kDa, were identified in rat adrenals by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot. bFGF was localized immunocytochemically in cells of the glomerulosa and the medulla. bFGF stimulated a 68-80% increase in the rate of DNA synthesis in adrenal capsule-glomerulosa preparations in vitro. Suramin (0.1 mM), a growth factor antagonist, blocked bFGF receptor interaction in vitro and, at 200 mg/kg given 5-7 days before adrenal surgery, blocked compensatory growth. Conversely, at 2.0 mg/kg, suramin significantly enhanced the compensatory growth response, perhaps caused by suramin-induced bFGF receptor upregulation, since suramin pretreatment also enhanced DNA synthesis in response to exogenous bFGF in vitro. These results suggest that bFGF may mediate proliferation in the compensatory adrenal growth response.
Total autonomic blockade eliminates the attenuated pressor response to angiotensin II in pregnant rats
Authors: Hines T. , Lindheimer M. D. , Barron W. M.
Published: December 2017

Pressor responses to angiotensin II (ANG II) are markedly attenuated in reflex-intact pregnant animals, a phenomenon widely attributed to intrinsic changes in vascular reactivity. To test the hypothesis that gestational augmentation of neural reflex activity contributes importantly to this phenomenon, changes in mean arterial pressure (MAP), cardiac output (CO), and total peripheral resistance (TPR) were compared during constant infusion (25-400 ng.kg-1.min-1) of ANG II in conscious virgin and pregnant rats, using a model of total autonomic blockade (chlorisondamine chloride and methscopolamine bromide), with restoration of baseline hemodynamics by infusion of norepinephrine. Basal CO was higher and TPR lower in pregnant (CO 121.8 +/- 3.8 ml/min; TPR 0.78 +/- 0.04 mmHg.ml-1.min) compared with virgin (CO 95.9 +/- 3.9 ml/min; TPR 1.05 +/- 0.08 mmHg.ml-1.min) rats (P < 0.005). Pressor responses to ANG II were similar in both groups of reflex-blocked animals due to comparable changes in TPR and CO (not significant by repeated-measures analysis of variance). Other experiments demonstrated that changes in MAP after bolus administration of ANG II did not differ in areflexic virgin and gravid rats. Thus in the absence of autonomic control ANG II has similar effects on systemic resistance in pregnant and nonpregnant rats, suggesting that reflex neural mechanisms contribute significantly to gestational changes in pressor responsiveness. These data further suggest that pregnancy is not accompanied by a generalized decrease in vascular reactivity to all pressor agents.
Sex difference in the antidiuretic activity of vasopressin in the rat
Authors: Wang Y. X. , Edwards R. M. , Nambi P. , Stack E. J. , Pullen M. , Share L. , Crofton J. T. , Brooks D. P.
Published: December 2017

A possible gender difference in the antidiuretic activity of vasopressin was studied in male and female Sprague-Dawley rats. Infusion of vasopressin (3-100 pg.kg-1.min) into conscious, chronically instrumented water-loaded rats resulted in a dose-dependent antidiuresis in both male and female rats. Male rats, however, were more than three times more sensitive to vasopressin than female rats. Thus the effective doses of vasopressin (pg.kg-1.min-1) to decrease urine flow to 30 microliters.min-1.100 g-1 (18 +/- 5 in males; 58 +/- 12 in females), to increase urine osmolality to 600 mosmol/kgH2O (35 +/- 5 in males; 119 +/- 15 in females), and to decrease free water clearance to 30 microliters.min-1.100 g-1 (8 +/- 3 in males; 28 +/- 7 in females) were significantly (P < 0.05) lower in males. Furthermore, in vitro studies in papillary collecting duct cells demonstrated a significantly higher density of vasopressin V2 receptors and a greater ability of vasopressin to stimulate adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in males than in females. Vasopressin V2-receptor density (maximum binding) was 359 +/- 47 and 238 +/- 22 fmol/mg in male and female rats, respectively (P < 0.05). There was no difference in apparent dissociation constants (Kd). Vasopressin resulted in a dose-dependent increase in cAMP accumulation in papillary collecting duct cells, and at the highest concentration of vasopressin used (10(-8) M) cAMP increased from 44 +/- 10 to 182 +/- 51 fmol/micrograms protein in males and from 30 +/- 4 to 91 +/- 18 fmol/micrograms protein in females (P < 0.05). (ABSTRACT TRUNCATED AT 250 WORDS)
The stomach is the etiologic organ for immobilization-induced hypocalcemia in rats
Authors: Aou S. , Ma J. , Shiramine K. , Hori T.
Published: December 2017

Our previous study revealed that the gastric vagus nerve plays an etiologic role in immobilization (IMB) stress-induced hypocalcemia. The purpose of the present study is to identify exactly what parts of the stomach are involved in the development of IBM-induced hypocalcemia and to determine whether or not gastric acid secretion is involved. A total gastrectomy, but not a resection of the upper intestine, eliminated the hypocalcemic effect of IMB. In addition, either an antrectomy (removal of the source of gastrin) or a fundectomy (depriving the origin of gastric histamine and gastric acid) was sufficient for eliminating IMB-induced hypocalcemia, while a partial (50%) fundectomy failed to suppress it. An intraperitoneal injection of galanin (an inhibitor of gastrin release) or ranitidine (a blocker of histamine H2-receptor) also suppressed the calcium-lowering effect of IBM, whereas omeprazole (an inhibitor of the proton pump) had no effect. These findings suggest that the antrum and the fundus of the stomach play essential roles in IMB-induced hypocalcemia through the vagus-induced release of gastrin and histamine but not through the secretion of gastric acid per se.
Meal initiation occurs after experimental induction of transient declines in blood glucose
Authors: Smith F. J. , Campfield L. A.
Published: December 2017

Previous studies have shown that a brief rise in plasma insulin followed by a transient fall and rise in blood glucose precede the initiation of feeding in nondeprived rats. In this study, a cholinergic agonist, bethanechol chloride, which is known to induce a brief spike in plasma insulin, was infused intravenously in an attempt to induce transient declines in blood glucose and meal initiation in free-feeding rats. When the blood glucose response to bethanechol chloride administration met the criteria for a transient decline in blood glucose, meal initiation occurred within 20 min in nine out of ten trials. However, if the blood glucose response to bethanechol chloride administration failed to meet the criteria for a transient decline in blood glucose, meal initiation did not occur. The frequency of successful induction of feeding was higher in the late light cycle (80%) compared with the early light cycle (14%) of the photoperiod. These results suggest that cholinergic stimulation can induce feeding only after a brief fall and rise in blood glucose. The blood glucose and behavioral responses to the cholinergic stimulus appear to be strongly dependent on the metabolic state of the animal. These results further strengthen the evidence for a causal relationship between transient declines in blood glucose and meal initiation in free-feeding rats.
Effect of competitive antagonism of NO synthetase on weight and food intake in obese and diabetic mice
Authors: Morley J. E. , Flood J. F.
Published: December 2017

Recent studies have suggested a role for nitric oxide (NO) in the regulation of food intake. The present studies were undertaken to examine the effects of the administration of a nitric oxide synthetase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on food intake and weight loss. Two genetically obese mice, the ob/ob and db/db strains, and their lean heterozygote littermate controls, ob/c and db/c, served as subjects. In the first experiment, we demonstrated that L-NAME (100 micrograms/kg) given twice over a feeding period of 7 h/day produced a small but significant weight loss in ob/ob mice but not in their lean-genotype controls (P < 0.05). In the second experiment, a higher dose of L-NAME (100 mg/kg), given twice daily, produced a marked effect on body weight, with the ob/ob mice losing approximately 10% of their body weight in 9 days. The ob/c mice showed a lesser decrease in body weight. Food intake was decreased on all 9 days in the ob/ob mice (P < 0.01). A small decrease in body weight and food intake was seen in db/db and db/c mice receiving L-NAME. These studies provide further evidence for a role of nitric oxide in the modulation of food intake and weight gain.
Hypoxia selectively excites vasomotor neurons of rostral ventrolateral medulla in rats
Authors: Sun M. K. , Reis D. J.
Published: December 2017

Systemic hypoxia [PaO2 27.3 +/- 1.8 (SE) mmHg] in anesthetized paralyzed rats reversibly increased within seconds the arterial pressure and activities of the sympathetic nerves and the reticulospinal vasomotor neurons of the rostral ventrolateral medulla (RVL). After peripheral chemodenervation, hypoxia also increased activity of the sympathetic nerves and doubled discharges of the vasomotor neurons while inhibiting a majority of the RVL respiratory neurons. Systemic hypercapnia was not effective in eliciting sympathoexcitatory responses. Iontophoresis of sodium cyanide stimulated the vasomotor and inhibited the respiratory neurons. In contrast, iontophoreses of H+, HCO3-, and lactate were without effects on activity of the vasomotor neurons. We conclude 1) hypoxia excites the vasomotor neurons by activating the arterial chemoreceptors and by activating intrinsic cellular mechanisms probably unrelated to accumulation of metabolic byproducts; 2) hypoxia may be the adequate stimulus exciting the RVL-spinal vasomotor and inhibiting the respiratory neurons during the cerebral ischemic response; and 3) these vasomotor neurons may be central oxygen detectors.
High-flow microinfusion: tissue penetration and pharmacodynamics
Authors: Morrison P. F. , Laske D. W. , Bobo H. , Oldfield E. H. , Dedrick R. L.
Published: December 2017

High-flow microinfusion provides a means for delivering macromolecules to large volumes of brain in easily obtainable time intervals. Slowly degraded approximately 180-kDa macromolecules, delivered at a constant volumetric flow rate of 3 microliters/min into homogeneous brain tissue (e.g., gray matter), would penetrate to a 1.5-cm radius in 12 h. The predicted concentration profile is relatively flat until it declines precipitously at the flow front. Hence, tissues are dosed rather uniformly, providing control over the undesired toxicity that may occur with alternative methods that depend on large concentration gradients for tissue transport. The penetration advantage of high-flow (convective) over low-flow (diffusive) microinfusion has been assessed at fixed pharmacodynamic effect. A 12-h high-flow microinfusion of a macromolecule degraded with a characteristic time of 33.5 h would provide 5- to 10-fold increases in volume over low-flow infusion and total treatment volumes > 10 cm3. Slower degradation rates would result in larger treatment volumes; more rapid degradation rates would reduce the volume but still favor convective over diffusive administration. This technique may be applicable to a variety of diagnostic and therapeutic agents such as radioimmunoconjugates, immunotoxins, enzymes, growth factors, and oligonucleotides.
Metabolic influences on satiety in rats receiving parenteral nutrition
Authors: Beverly J. L. , Meguid M. M. , Yang Z. J. , Yue M. X. , Fetterman B. L.
Published: December 2017

Food intake is reduced during parenteral nutrition (PN) proportionally to the amount of calories or composition of the solution infused. The relative importance of infused glucose and lipid, 50 and 30% of PN kilocalories, respectively, in reducing food intake during PN was examined. Glycolysis, fatty acid oxidation, or both were acutely disrupted with 2-deoxy-D-glucose (2-DG) and mercaptoacetate (MA). Rats receiving intravenous infusions of saline or a PN solution providing 100% of total daily calories (PN-100) received a single intraperitoneal injection of saline, 2-DG, and/or MA during the early light phase. 2-DG (1.4 or 2.2 mmol/kg) did not initiate feeding in PN-100 rats, although hyperglycemia was evident in all rats 1 h after 2-DG. Food intake of PN-100 rats after MA (0.4 mmol/kg) was approximately 50% that of control rats. When 2-DG (1.4 mmol/kg) and MA (0.4 mmol/kg) were administered concomitantly, PN-100 and control rats consumed the same amount of food. During PN-100, rats appeared to be more sensitive to losing metabolic energy derived from lipid than from glucose.
Kinetics of active efflux via choroid plexus of beta-lactam antibiotics from the CSF into the circulation
Authors: Ogawa M. , Suzuki H. , Sawada Y. , Hanano M. , Sugiyama Y.
Published: December 2017

To examine the role of the choroid plexus in eliminating organic anions from the cerebrospinal fluid (CSF), a kinetic study was performed both in in vivo and in vitro experiments using [3H]benzylpenicillin (PCG) as a model compound. In vivo, after intracerebroventricular administration, [3H]PCG was eliminated from the CSF much more rapidly than [14C]mannitol. Analysis of the elimination clearance from the CSF revealed that 12 and 24% of the disappearance of [3H]PCG can be accounted for by convective loss at a rate equivalent to CSF turnover, and by diffusional loss across the ependymal surface into the brain extracellular space, respectively. Approximately two-thirds of [3H]PCG elimination was due to a saturable process [Michaelis constant (Km) = 43.0 +/- 17.8 microM, maximum velocity (Vmax) = 619 +/- 286 pmol.min-1 x rat-1]. These kinetic parameters obtained in vivo were comparable to those determined previously in vitro, i.e., [3H]PCG was accumulated by the isolated rat choroid plexus via an active transport mechanism (Km = 58 microM, Vmax = 504 pmol.min-1 x rat-1; H. Suzuki, Y. Sawada, Y. Sugiyama, T. Iga, and H. Hanano, J. Pharmacol. Exp. Ther. 242: 660-665, 1987). Furthermore, other organic anions (probenecid, ampicillin, cefodizime, cefotaxime, and ceftriaxone) reduced the transport of [3H]PCG in a dose-dependent manner both in vivo and in vitro. A good correlation was observed between the log inhibition constant (Ki) values obtained for these ligands in vivo and in vitro (r = 0.94, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Abnormalities in the renal and vascular responses to LBNP in humans with early diabetes
Authors: Miller J. A. , Floras J. S. , Zinman B. , Skorecki K. L. , Logan A. G.
Published: December 2017

Plasma atrial natriuretic factor (ANF) concentrations are increased in subjects with insulin-dependent diabetes mellitus (IDDM). A potential contribution of ANF to the maintenance of abnormalities in renal hemodynamic function has been considered but not proven in human diabetic subjects. The aim of these experiments was to determine the response of renal blood flow (RBF), glomerular filtration rate (GFR), filtration fraction (FF), and urinary sodium excretion (UNaV) to a reduction of plasma ANF concentrations induced by application of nonhypotensive lower body negative pressure (LBNP) in a group of subjects with early, uncomplicated, well-controlled IDDM compared with control subjects. Baseline supine measurements before LBNP revealed the diabetic subjects to have a significantly higher plasma ANF (31 +/- 2 vs. 24 +/- 2 pg/ml, P = 0.05). GFR tended to be higher (118 +/- 11 vs. 104 +/- 9 ml/min) and UNaV tended to be depressed (188 +/- 25 vs. 240 +/- 25 mumol/min) despite equal sodium intake, but not significantly so. In addition IDDM subjects exhibited significantly lower baseline plasma norepinephrine (PNE) concentrations (0.91 +/- 0.20 vs. 1.60 +/- 0.2 nmol/l, P = 0.03). Forearm vascular resistance (FVR) was not significantly different between the two groups (29 +/- 5 vs. 33 +/- 5 units). LBNP induced comparable decreases in ANF and central venous pressure (CVP) in both groups. The anticipated renal response to ANF reduction (declines in GFR, FF, and UNaV) occurred only in the normal control group. The percent decline in GFR (11% vs. 34.5%, P = 0.01) was markedly attenuated in IDDM subjects. The expected reflexive increase in PNE and FVR also did not occur in IDDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of lateral hypothalamus on fluid, electrolyte, and cardiovascular responses to activation of the MSA
Authors: Haibara A. S. , Saad W. A. , Menani J. V. , Camargo L. A. , Renzi A.
Published: December 2017

In this study we investigated the influence of electrolytic lesion or of opioid agonist injections into the lateral hypothalamus (LH) on the dipsogenic, natriuretic, kaliuretic, antidiuretic, pressor, and bradycardiac effects of cholinergic stimulation of the medial septal area (MSA) in rats. Sham- and LH-lesioned male Holtzman rats received a stainless steel cannula implanted into the LH. Other groups of rats had cannulas implanted simultaneously into the MSA and LH. Carbachol (2 nmol) injection into the MSA induced water intake, pressor, and bradycardic responses. LH lesion reduced all of these effects (1-3 and 15-18 days). Previous injection of synthetic opiate agonist, FK-33824 (100 ng), into the LH reduced the water intake, natriuresis, kaliuresis, and pressor responses induced by carbachol injected into the MSA. These data show that both electrolytic lesion or injection of an opiate agonist in the LH reduces the fluid-electrolyte and cardiovascular responses to cholinergic activation of the MSA. The involvement of LH with central excitatory and inhibitory mechanisms related to fluid-electrolytic and cardiovascular control is suggested.
Blunted effect of ANP on hematocrit and plasma volume in streptozotocin-induced diabetes mellitus in rats
Authors: Valentin J. P. , Sechi L. A. , Humphreys M. H.
Published: December 2017

Atrial natriuretic peptide (ANP) infusion increases hematocrit and decreases plasma volume by inducing a transfer of plasma fluid from the vascular to the interstitial compartment. Diabetes mellitus is associated with resistance to the renal actions of ANP. We explored the possibility that the extrarenal responses to ANP may also be altered in the diabetic state by measuring changes in arterial pressure and hematocrit during infusion of ANP (1 microgram.kg-1 x min-1 for 45 min) into anesthetized, acutely nephrectomized rats 2-3 wk after induction of diabetes from intravenous streptozotocin (STZ) injection (60 mg/kg). Blood glucose was significantly elevated in diabetic rats when compared with control and insulin-treated diabetic rats. Arterial pressure during ANP infusion decreased similarly in control; diabetic, and insulin-treated diabetic rats (by 7.6 +/- 1.6, 9.6 +/- 1.9, and 8.2 +/- 2% respectively; all P < 0.002). In control rats, hematocrit increased progressively to a maximum value of 9.5 +/- 0.9% as a result of the infusion, corresponding to a decrease in plasma volume of 16.3 +/- 1.3%. In contrast, the ANP-induced increase in hematocrit was markedly blunted in diabetic rats (1.6 +/- 0.8%; P < 0.0001 vs. ANP infusion in control rats). Reducing the hyperglycemia in diabetic rats by insulin therapy restored the increase in hematocrit in response to ANP (8.5 +/- 1.1%; P < 0.0001 vs. ANP infusion in diabetic rats and P = NS vs. control rats). ANP infusion increased plasma ANP levels to the same extent in the three groups, whereas plasma guanosine 3',5'-cyclic monophosphate (cGMP) was significantly less in diabetic as compared with control and insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Antipyresis caused by stimulation of vasopressinergic neurons and intraseptal or systemic infusions of gamma-MSH
Authors: Bock M. , Roth J. , Kluger M. J. , Zeisberger E.
Published: December 2017

Antipyretic properties have been ascribed to arginine vasopressin (AVP), and the site where its antipyretic effects are mediated in the brain was identified as the ventrolateral septum of the limbic system. In guinea pigs, the majority of AVP projections to the septum originate from parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). Electrical stimulation of the PVN with 10-s trains of current pulses (duration 1 ms, frequency 20 Hz, amplitude 8 V, current 0.205 +/- 0.017 mA) reduced the febrile response to an intramuscular injection of 20 micrograms/kg lipopolysaccharide (LPS from Escherichia coli, 0111: B4) by 54% compared with unstimulated animals. This reduction in fever by electrical PVN stimulation was partly reversed by a simultaneous intraseptal microinfusion of the vasopressinergic V1-receptor antagonist d(CH2)5[Tyr(Met)2]AVP at a concentration of 10(-5) mol for 6 h with an infusion speed of 0.1 microliter/min. We further investigated the effects of intraseptal microinfusions or systemic infusions of the gamma-melanocyte-stimulating hormone (gamma-MSH), a derivative of the proopiomelanocortin, on LPS-induced fever. Intraseptal microinfusions of gamma-MSH at a concentration of 10(-5) mol/l for 6 h with an infusion speed of 0.1 microliter/min caused a 38% reduction in fever. A significantly greater 57% reduction in fever was observed when the intraseptal microinfusion of gamma-MSH was combined with electrical stimulation of the PVN (for parameters see above). A systemic infusion of 0.261 mumol gamma-MSH for 6 h reduced LPS fever to approximately 50% compared with animals infused with vehicle (0.9% saline).(ABSTRACT TRUNCATED AT 250 WORDS)
An electrophysiological and morphological study of esophageal motoneurons in rats
Authors: Kruszewska B. , Lipski J. , Kanjhan R.
Published: December 2017

Previous anatomic studies have shown that motoneurons supplying the striated musculature of the esophagus form a tightly grouped cluster in the rostral portion of the nucleus ambiguus, known as the compact formation. This study, conducted in anesthetized rats, presents the first in vivo intracellular and extracellular recordings from this group of motoneurons, which were identified by antidromic stimulation directly from the esophagus (latency 7-68 ms). The motoneurons were silent at rest, and those impaled intracellularly (n = 44) showed no respiratory modulation of their membrane potential. Intracellular labelling with Lucifer Yellow (n = 3) or Neurobiotin (n = 15) revealed multipolar somas with longitudinally oriented dendritic trees mainly confined to the compact formation. No axon collaterals were found. When swallowing-like activity was induced by muscarine applied to the dorsal medullary surface, the motoneurons displayed bursting activity, with the majority of bursts occurring during expiration. These results show that antidromic stimulation of esophageal motoneurons with an electrode inserted into the esophagus provides a simple way of identifying these motoneurons. In the absence of pharmacological stimulation, these motoneurons receive no respiratory-modulated synaptic input, in contrast to adjacent motoneurons in the semicompact formation (supplying the upper airways), which are known to display respiratory activity. However, some synchronization of respiratory and swallowing-like activity was observed after pharmacological activation of the swallowing pattern generator in the dorsal medulla.