bluuebunny/crossref_metadata_2025 huggingface dataset:
Abdominal vagal mediation of the satiety effects of exogenous and endogenous cholecystokinin in rats
Authors: Reidelberger R. D.
Published: December 2017

The hypothesis that peripherally administered cholecystokinin C-terminal octapeptide (CCK-8) and endogenous CCK act by the same abdominal vagal mechanism to produce satiety was tested by injecting rats with CCK-8 or the type A CCK receptor antagonist MK-329 after they had received bilateral subdiaphragmatic vagotomies. CCK-8 (8 nmol/kg ip) inhibited 1-h food intake by 60%; vagotomy and MK-329 (0.5 mg/kg sc) each completely blocked this effect. In contrast, vagotomy did not alter the stimulatory effect of MK-329 (0.5 mg/kg sc) on feeding; 3-h cumulative intake in control and vagotomized animals was increased by 25 and 34%, respectively. These results suggest that satiety is mediated in part by an endogenous CCK action that is independent of abdominal vagal innervation.
Effects of arterial pressure on drinking and urinary responses to intracerebroventricular angiotensin II
Authors: Thunhorst R. L. , Johnson A. K.
Published: December 2017

These experiments examined the dipsogenic responses of rats to intracerebroventricularly administered angiotensin II (ANG II) under normotensive and hypotensive conditions. Intravenous infusion of the vasodilator drug minoxidil (25 micrograms.kg-1.min-1), combined with the angiotensin converting enzyme inhibitor captopril (0.33 mg/min), both reduced blood pressure and prevented endogenous ANG II formation. Central infusions with ANG II (4 or 16 ng/h) began 60 min later, and the intravenous and intracerebroventricular infusions ran concurrently for another 90 min. Mean arterial pressure (MAP), water intake, urine volume (UV) and electrolyte excretion were measured throughout. Water intakes to both doses of intracerebroventricular ANG II were increased, and UV and electrolyte excretion were reduced during hypotensive conditions compared with normotensive conditions. Thus the increased water intakes occurred despite increased fluid retention. It is concluded that arterial hypotension enhances the dipsogenic effects of centrally administered ANG II, possibly through baroreceptor-mediated mechanisms.
Fourth ventricular injection of selective bombesin receptor antagonists facilitates feeding in rats
Authors: Flynn F. W.
Published: December 2017

Exogenous bombesin (BN)-like peptides exert their effects on feeding through caudal brain stem BN-like peptides and their receptors. To determine if endogenous BN-like peptides are involved in the control of feeding and exert their actions on caudal brain stem neurons, nondeprived rats were administered fourth ventricular injections of either saline or BN receptor antagonists in the following doses: 5 and 25 ng [D-Phe12,Leu14]BN or 5 ng [D-Phe6]BN(6-13)methyl ester. Milk intake was measured every 5 min and each animal's behavior (eating, grooming, exploring, resting) was monitored every 1 min for 60 min. Compared with saline injections, fourth ventricular injections of 25 ng [D-Phe12,Leu14]BN and 5 ng [D-Phe6]BN(6-13)methyl ester reliably facilitated milk intake. The enhanced milk intake was evident within 5 min after the injection and persisted throughout the 1-h intake test. The behavioral sequence following fourth ventricular injections of saline and the antagonists that facilitated feeding were similar. Injections of [D-Phe12,Leu14]BN and [D-Phe6]BN(6-13)methyl ester did not produce a generalized arousal. The results indicate that food-contingent, endogenous BN-like peptides contribute to the termination of feeding and exert their behavior-controlling actions on BN-like peptide receptors in the vicinity of the fourth ventricle.
Relationship between dietary sodium intake, hemodynamics, and cardiac mass in SHR and WKY rats
Authors: Frohlich E. D. , Chien Y. , Sesoko S. , Pegram B. L.
Published: December 2017

To study the effects of sodium intake on circulatory homeostasis and cardiac structure, changes in cardiac mass, systemic hemodynamics, and organ blood flows were determined in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats after 10 wk of controlled dietary intake of low sodium (0.01%), standard sodium (0.44%), and high sodium (2 levels: 1.44 and 4%). Systemic and regional hemodynamics were measured in conscious rats using the radioactive microsphere reference method. The various dietary sodium manipulations did not cause any changes in systemic and regional hemodynamics in the WKY rats. In contrast, the high-sodium diets increased arterial pressure and total peripheral resistance progressively in the SHR rats while decreasing cardiac index, heart rate, and organ blood flows to heart, kidneys, and splanchnic area. The higher sodium intake (4%) increased total and left ventricular mass index in both the SHR and the WKY rats even though hemodynamics of the WKY rats remained unchanged. These data indicate that the high-sodium diet, in addition to producing general vasoconstriction and exacerbation of hypertension, increased cardiac mass further in SHR rats; it also increased cardiac mass in the WKY rats independent of arterial pressure changes, suggesting that high sodium intake may be an independent pathogenetic factor for the development of cardiac hypertrophy.
Lick rate analysis of sodium taste-state combinations
Authors: Breslin P. A. , Kaplan J. M. , Spector A. C. , Zambito C. M. , Grill H. J.
Published: December 2017

The combined effects of taste and physiological state on lick rate for NaCl were systematically evaluated in two experiments. In experiment 1 the lick rates of six groups of rats (Sprague-Dawley) were recorded during the first 3 min of a NaCl drinking bout, where each group received a different concentration. Half of the rats were depleted by injections of the diuretic-natriuretic furosemide (10 mg ip), whereas the other half were not. The inverted U-shaped concentration-response functions for sodium-replete rats peaked approximately at isotonicity. The replete lick rate function was uniformly elevated for rats examined in the sodium-depleted state. In experiment 2 each rat received access to all six solutions within a 40-min test session. Rats were tested twice, once in positive and once in negative sodium balance. The solutions were repeatedly presented in counterbalanced order in a series of 10-s exposures. The replete and deplete functions of the within-group study closely resembled those of the between-group study. When the deplete rats' function was divided into three segments coinciding with the beginning, middle, and end of the 40-min session, the functions were shifted down vertically but retained their shape. In general, sodium-state level dramatically affected the absolute lick rates but did not appear to shift the location of the concentration-response function along the horizontal (i.e., concentration) axis. The form of the function appears to have been determined by oral factors alone.
Nutritional and metabolic adaptations to prolonged sleep deprivation in the rat
Authors: Everson C. A. , Wehr T. A.
Published: December 2017

To understand how and why sleep deprivation is physically harmful, we explored the possible causal relationship between its two main effects, 1) negative energy balance and 2) a composite of symptoms that resemble protein malnutrition, both of which occur despite increased food consumption. We provided balanced diets augmented with either protein or calories (by increased fat content) to freely moving rats. Interactions between sleep deprivation symptoms and energy and protein supplies were assessed from measurements of body weight regulation, consumption of macronutrients, clinical chemistry and hematology profiles, and physical appearance. The results indicate that sleep deprivation causes malnutrition, which is secondary to increased energy expenditure. Even though food consumption remained normal in sleep-deprived rats fed a diet of high protein-to-calorie ratio, body weight loss was more than 16% of baseline, development of skin lesions was hastened, and longevity was shortened by 40% compared with sleep-deprived rats fed the calorie-augmented diet. Food consumption of the calorie-fed rats was lower during baseline than that of the protein-fed group but during sleep deprivation increased to amounts 250% of normal without net body weight gain. Despite a fat-laden diet the calorie-fed hyperphagic group did not have abnormal levels of plasma cholesterol, triglycerides, or glucose, indicating accelerated turnover of nutrients. As would be consistent with calorie malnutrition, pronounced clinical chemistry or hematological abnormalities were not found in any group. Beneficial effects of the calorie-augmented diet are attributed to 1) caloric density of fat, 2) induction of hyperphagia, and 3) efficiency of utilization of fat. We conclude that diet composition interacts strongly with sleep deprivation, affecting the time course and development of pathologies, whereas it exerted negligible influence on body weight regulation under normal conditions.
Ventrolateral medulla in spontaneously hypertensive rats: role of angiotensin II
Authors: Muratani H. , Ferrario C. M. , Averill D. B.
Published: December 2017

We investigated whether angiotensin II (ANG II), endogenous to the ventrolateral medulla (VLM), contributes to cardiovascular regulation in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The action of ANG II endogenous to the VLM was examined by microinjection of 100 pmol of [Sar1,Thr8]ANG II into either the rostral (R) or caudal (C) VLM. This ANG II antagonist caused depressor and bradycardic responses in the RVLM and pressor and tachycardic responses in the CVLM. The magnitude of the blood pressure responses was significantly greater (P < 0.01 in RVLM and P < 0.05 in CVLM) in SHRs (-27 +/- 3 mmHg in RVLM and 29 +/- 4 mmHg in CVLM) than in WKY rats (-17 +/- 1 and 17 +/- 2 mmHg, respectively). Suppression of tonic activity of RVLM neurons by bilateral injection of muscimol in the RVLM showed that the pressor response produced by ANG II antagonist injection in the CVLM required the integrity of rostral pressor neurons. The present data suggest that ANG II endogenous to RVLM and CVLM acts as a tonic excitatory agent on vasomotor neurons of the VLM. The contribution of ANG II in the RVLM and CVLM to the prevailing level of blood pressure was significantly (P < 0.01) larger in SHRs vs. WKY rats when the effect of ANG II blockade was measured as the change in blood pressure. Blockade of gamma-aminobutyric acid (GABA)A receptors in the RVLM showed that inhibitory GABAergic input to the RVLM was not diminished in this strain.(ABSTRACT TRUNCATED AT 250 WORDS)
Microcirculatory effects of hypoxic and hypercapnic vasoconstriction in frog skin
Authors: Malvin G.
Published: December 2017

The effects in frog (albino Xenopus laevis) skin of hypoxic and hypercapnic vasoconstriction on the following microcirculatory parameters were determined: capillary red blood cell flux, capillary red blood cell velocity, perfused capillary density, lineal red blood cell density, and the temporal heterogeneity of capillary red blood cell velocities. All of these parameters affect the gas exchange characteristics of respiratory organs. Measurements were made by fluorescent video microscopy of a 1.5-cm2 region of skin exposed to different gas mixtures (air, O2, N2, 5% CO2-95% air, 5% CO2-95% N2). N2 caused red blood cell flux and velocity to fall to 52 +/- 10% (P < 0.05) and 47 +/- 10% (P < 0.01), respectively, of those values during air exposure. Five percent CO2 caused capillary red blood cell flux and velocity to decrease by 51 +/- 11% (P < 0.05) and 43 +/- 11% (P < 0.01), respectively. Fluxes (P < 0.01) and velocities (P < 0.01) were also less with 5% CO2-95% N2 than with air. There were no significant differences in flux and velocity between N2, 5% CO2-95% air and 5% CO2-95% N2 (P > 0.1). There was no significant difference in flux or in velocity between O2 and air (P > 0.1). Gas composition had no significant effect on lineal red blood cell density (P > 0.35) or the density of perfused capillaries (P > 0.22). The heterogeneity of cell velocities was significantly greater with N2 than with the other gases (P < 0.01). There was no significant difference in red blood cell velocity heterogeneity between the other gases (P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)
Glucoprivation induces anestrus and lipoprivation may induce hibernation in Syrian hamsters
Authors: Schneider J. E. , Friedenson D. G. , Hall A. J. , Wade G. N.
Published: December 2017

Previous results supported the notion that estrous cycles in Syrian hamsters are responsive to the general availability of metabolic fuels, rather than to either fatty acid or glucose availability per se. To test this idea, we monitored estrous cycles in hamsters that were fed ad libitum and treated with a range of doses of 2-deoxy-D-glucose (2-DG), an inhibitor of glucose utilization. Hamsters treated with 2-DG at doses ranging from 750-1,250 mg/kg showed normal estrous cycles, but higher doses (1,750 or 2,000 mg/kg) induced anestrus. While it is clear from these data that estrous cycles are affected by glucoprivation, it is not clear whether they are responsive to decreased fatty acid availability. Groups of hamsters were fed ad libitum and treated with a range of doses of methyl palmoxirate (MP), an inhibitor of fatty acid utilization. Some of the hamsters that received the highest doses became torpid and thus were not tested for lordosis. None of the euthermic, MP-treated hamsters became anestrous. Other experiments examined the role of glucose availability in fasted hamsters. Hamsters with a high body fat content were protected from fasting-induced anestrus. In contrast, fat food-deprived hamsters treated with low doses of 2-DG (750 mg/kg) became anestrous. Thus fatty acids mobilized from adipose tissue did not prevent fasting-induced anestrus when glucose utilization was blocked. One interpretation is that during fasting fatty acid utilization spares glucose for other tissues involved in the control of estrous cycles.(ABSTRACT TRUNCATED AT 250 WORDS)
Relationship between renal perfusion pressure and blood flow in different regions of the kidney
Authors: Mattson D. L. , Lu S. , Roman R. J. , Cowley A. W.
Published: December 2017

The present study examined the autoregulation of blood flow in different regions of the renal cortex and medulla in volume-expanded or hydropenic anesthetized rats. Blood flow was measured in the whole kidney by electromagnetic flowmetry, in the superficial cortex with implanted fibers and external probes for laser-Doppler flowmetry, and in the deep cortex and inner and outer medulla with implanted fibers for laser-Doppler flowmetry. At renal perfusion pressure > 100 mmHg, renal blood flow, superficial cortical blood flow, and deep cortical blood flow were all very well autoregulated in both volume-expanded and hydropenic rats. Inner and outer medullary blood flow were also well autoregulated in hydropenia, but blood flow in these regions was very poorly autoregulated in volume-expanded animals. As renal perfusion pressure was decreased below 100 mmHg in volume-expanded and hydropenic animals, renal blood flow, superficial and deep cortical blood flow, and inner and outer medullary blood flow all decreased. The results of these experiments demonstrate that blood flow in both the inner and outer portions of the renal medulla of the kidney is poorly autoregulated in volume-expanded rats but well autoregulated in hydropenic animals. In contrast, blood flow in all regions of the renal cortex is well autoregulated in both volume-expanded and hydropenic animals. These results suggest that changes in resistance in the postglomerular circulation of deep nephrons are responsible for the poor autoregulation of medullary blood flow in volume expansion despite well autoregulated cortical blood flow.
Prevention of secondary cardiovascular instability after intestinal ischemia and reperfusion improves survival
Authors: O'Neill P. J. , Cobb L. M. , Steigman C. K. , Chaudry I. H.
Published: December 2017

Previous studies of small intestinal ischemia and reperfusion (I/R) in immature rats report secondary systemic organ injury and low survival rates; however, in these studies the cardiovascular stability of the rat was not established. To prevent the secondary hemodynamic deterioration accompanying intestinal I/R, we have developed a model that utilizes aggressive fluid resuscitation. Under anesthesia, 4-wk-old male Sprague-Dawley rats (n = 189) underwent 90 min of I/R (superior mesenteric artery occlusion) or sham (SH) operation while receiving lactated Ringer with 5% dextrose at 15 (IR15, SH15) or 65 (IR65, SH65) ml.kg-1 x h-1 i.v. The results indicate that aggressive fluid resuscitation in the IR65 group significantly attenuated the hypotension, hemoconcentration, metabolic acidosis, and amount of gross bowel injury observed in the IR15 group, while increasing postreperfusion renal and intestinal blood flow, prolonging survival time of nonsurvivors, and improving overall group survival. These findings suggest that maintenance of hemodynamic stability is necessary in models of bowel I/R. Furthermore, this model allows for selective study of the isolated effects of intestinal I/R without the additional complications resulting from secondary cardiovascular instability.
Gastric branch vagotomy blocks nutrient and cholecystokinin-induced suppression of gastric emptying
Authors: Schwartz G. J. , Berkow G. , McHugh P. R. , Moran T. H.
Published: December 2017

A role for the vagus nerve in the emptying of intragastric nutrients and the gastric inhibitory actions of the brain-gut peptide cholecystokinin (CCK) has been proposed. To directly assess the role of the gastric vagal branches in these actions, we compared the emptying of 5-ml nutrient and nonnutrient gastric loads in male rats in which both branches of the gastric vagus nerves were cut (GVX, n = 7) with emptying in surgical control (n = 8) rats. Gastric emptying of saline was also examined in both groups after intraperitoneal administration of 8 micrograms/kg CCK. In control rats, high osmolarity, low pH, and caloric density all significantly decreased gastric emptying compared with the emptying of physiological saline. In addition, fat (oleic acid) and protein (peptone) loads emptied significantly more slowly than isocaloric carbohydrate (glucose) loads. Gastric branch vagotomy completely blocked the suppression of emptying produced by fat, protein, carbohydrate, and acid loads. In addition, GVX attenuated the ability of hyperosmotic nutrient and nonnutrient loads to inhibit emptying to the same degree, irrespective of their caloric content. Finally, in intact rats, CCK significantly inhibited the emptying of physiological saline, and gastric vagotomy abolished this suppression. Taken together, these results are consistent with the proposals that 1) the controlled emptying of caloric, hyperosmotic, and acidic solutions is dependent on gastric vagal branches, and 2) exogenous CCK relies on an intact vagal pathway in the control of gastric emptying.
Restricted food access and light-dark: impact of conflicting zeitgebers on circadian rhythms of the rabbit
Authors: Jilge B. , Stahle H.
Published: December 2017

Free-running circadian rhythms of rabbits were exposed to a 11:55-11:55-h light-dark (LD) schedule. After complete entrainment (63 +/- 22 days), the predominantly nocturnally active rabbits were exposed to an additional zeitgeber, restricted food access (RF), which was imposed during the light period. In five animals RF had the same period (T) as the LD cycle (23:50 h), and in five other animals TRF was 24:10 h. At a period of 23:50 h for both zeitgebers, the rhythms of four animals were stably entrained to RF, while in one animal a component of the rhythm broke away from RF and entrained to the LD zeitgeber. In animals exposed to zeitgebers of different periods most of the activity rhythm also entrained to RF, but 20 +/- 7% of the activity entrained to the LD zeitgeber. The light-entrained activity component merged with the RF component when the zeitgebers crossed, and decomposition occurred when the phase difference exceeded 4-6 h. The results indicate that two circadian oscillator systems exist in the rabbit, one entrained by light-dark cycles and the other by feeding-fasting cycles. Both exert common control over a number of overt behavioral rhythms.
Functional adaptation of different rat skeletal muscles to weightlessness
Authors: Stevens L. , Mounier Y. , Holy X.
Published: December 2017

The adaptation to weightlessness of two postural muscles, the slow soleus (SOL) and the fast gastrocnemius lateralis (GL), and a fast muscle used in movements, the extensor digitorum longus (EDL), was studied on five adult Wistar rats. The animals exposed to 14-day spaceflight aboard COSMOS 2044, designated as flight (F), were compared with synchronous (S) animals. The experiments were performed on single skinned fibers whose functional properties were studied. After weightlessness, the SOL exhibited two populations of fibers according to their Sr2+ affinities: 40% remained slow (Fs) and 60% acquired fast-type properties (Ff). Both S and F GL and EDL showed a single distributed population of fast fibers. SOL fibers atrophied insofar as they showed a significant reduction in fiber diameter and absolute maximal tension Po (mg) but not in Po expressed in kg/cm2. GL fibers showed no change in fiber diameter but a decrease in Po in mg and kg/cm2. EDL fibers were not atrophied by weightlessness. The tension/Ca concentration relationships of the Ff SOL and F GL fibers were shifted to the right, indicating a decrease in their Ca2+ affinity. An increase in the contraction kinetics was described for the SOL fibers after weightlessness, whereas no significant modification was found for the GL and EDL. Collectively, the data suggested that the adaptive changes subsequent to weightlessness were more dependent on the muscle function than on the fiber type, since both postural SOL and GL were modified.
Cardiac but not pulmonary receptors mediate depressor response to IV phenyl biguanide in conscious rabbits
Authors: Bell L. B. , O'Hagan K. P. , Clifford P. S.
Published: December 2017

Phenyl biguanide (PBG) stimulates pulmonary and cardiac receptors in the cat and rabbit. Previous reports have suggested that pulmonary receptors mediate the reflex respiratory responses and cardiac receptors mediate the reflex hypotension and bradycardia. Using selective denervation of the lung (LDX) and intrapericardial procaine to block cardiac nerves (CDX), we investigated the specific role of pulmonary and cardiac receptors in the reflex response to PBG infusion (60 micrograms/kg iv) in the conscious rabbit. Breathing frequency, arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were recorded before and after LDX and CDX. Before LDX and CDX, PBG infusion produced tachypnea, hypotension, and bradycardia. This was accompanied by a withdrawal of RSNA to a level not different from that evoked by ganglionic blockade. These responses were preserved after LDX but were abolished after CDX with intrapericardial procaine. Intrapericardial infusion of PBG produced no response. These results indicate that in conscious rabbits both the respiratory and cardiovascular responses to PBG infusion are mediated by cardiac receptors not accessible from the epicardial surface. Furthermore, the reflex hypotension is mediated largely by withdrawal of sympathetic nerve activity resulting in a decreased peripheral resistance.
Force potentiation in respiratory muscles: comparison of diaphragm and sternohyoid
Authors: Van Lunteren E. , Vafaie H.
Published: December 2017

Coordinated contraction of thoracic and pharyngeal upper airway respiratory muscles optimizes ventilation, whereas pharyngeal muscle dysfunction may lead to obstructive apneas during sleep. We hypothesized that the force potentiation exhibited by the pharyngeal respiratory muscle, the sternohyoid, in keeping with its faster contractile kinetics, would be greater than that of the thoracic respiratory muscle, the diaphragm. Rat muscles were studied in vitro at 37 degrees C with three force-potentiating protocols: posttetanic twitch potentiation, staircase phenomenon (twitch potentiation), and a classic fatigue paradigm. The sternohyoid had a faster isometric contraction time, a more rightward located force-frequency relationship, and both a more rapid onset and a greater degree of fatigue than the diaphragm. During the early portion of the fatigue protocols, the increase in force was significantly greater for the sternohyoid muscle than the diaphragm (e.g., 33 vs. 3% increase at 20 Hz, P < 0.005). During repetitive twitches at 2, 3, and 5 Hz (staircase test), sternohyoid muscle force increased more than diaphragm force at the higher stimulus frequencies (e.g., by 38 vs. 23% at 5 Hz, P < 0.01). After brief tetanic stimuli, sternohyoid twitch force increased more than diaphragm twitch force (e.g., 73 vs. 14% increase after 125 Hz tetanus, P < 0.005). These data indicate that force potentiation is exhibited by both diaphragm and sternohyoid respiratory muscles, but to different extents, when activated repetitively.(ABSTRACT TRUNCATED AT 250 WORDS)
Fish oil n-3 fatty acids selectively limit the hypertrophy of abdominal fat depots in growing rats fed high-fat diets
Authors: Belzung F. , Raclot T. , Groscolas R.
Published: December 2017

Because dietary n-3 polyunsaturated fatty acids (n-3 PUFA) from fish oils have profound effects on lipid metabolism, we examined whether they influence the growth of adipose tissue at different locations in growing rats. Rats were fed for 4 wk on high-fat (HF) diets (20% fat) containing very low (L), medium (M), and high (H) amounts of n-3 PUFA but similar amounts of saturated fatty acids and n-6 PUFA. A fourth group was fed a standard laboratory diet (control group) to estimate changes in adipose tissue mass related to growth. At the end of the dietary treatment, the lipid mass (LM) of the four major adipose depots (subcutaneous, SC; mesenteric, MES; retroperitoneal, RP; epididymal, EPI) and total adiposity were significantly higher in each of the three HF groups than in the control group. The lipid gain in EPI was due to fat cell hypertrophy alone, whereas RP showed both hypertrophy and hyperplasia. Energy intake, fatty acid excretion, and body mass were the same in the three groups fed HF diets. Similarly, there was no difference in the LM or in lipid gains specifically caused by HF feeding of SC and MES between the HF groups. In contrast, the LM of RP was significantly lower in the H than in the L and M groups (50 and 30%, respectively). The LM of EPI was also 30% lower in the H than in the L group.(ABSTRACT TRUNCATED AT 250 WORDS)
Distribution and activity of dogfish NPY and peptide YY in the cardiovascular system of the common dogfish
Authors: Bjenning C. , Hazon N. , Balasubramaniam A. , Holmgren S. , Conlon J. M.
Published: December 2017

Neuropeptide Y is present in sympathetic nerves in the mammalian cardiovascular system. This study has investigated the distribution of neuropeptide Y in the cardiovascular and gastrointestinal systems and the effect of dogfish neuropeptide Y and related peptides on cardiovascular tissue of an elasmobranch fish, the common dogfish (Scyliorhinus canicula). Neuropeptide Y-like immunoreactivity is present in varicose nerve fibers innervating dogfish gut and cardiovascular tissue and in endocrine cells of the dogfish spiral intestine. Dogfish neuropeptide Y, dogfish peptide YY, and porcine neuropeptide Y contract the dogfish afferent branchial artery in a concentration-dependent manner. The effect is not inhibited by the presence of tetrodotoxin or by removal of the endothelium. The mammalian Y1 receptor selective agonist [Leu31Pro34]NPY but not the mammalian Y2 receptor selective agonist neuropeptide Y-(13-36) peptide has vasoconstrictor properties in this system, suggesting that the receptor mediating the vasoconstriction resembles the mammalian Y1 receptor more than the Y2 receptor.
Rapid-onset "need-free" sodium appetite after lesions of the dorsomedial medulla
Authors: Edwards G. L. , Beltz T. G. , Power J. D. , Johnson A. K.
Published: December 2017

Previous studies indicate the dorsomedial hindbrain is important in the maintenance of fluid balance. Lesions centering on the area postrema (AP) result in enhanced ad libitum intake of concentrated saline solutions on a 24-h basis as well as enhanced excretion of water and electrolytes. Additionally, rats with lesions of the AP are reported to have an exaggerated behavioral response to dipsogenic challenges that mimic depletion of the extracellular fluid compartment. In the studies reported here, we have observed that rats with lesions of the AP and immediately adjacent nucleus of the solitary tract consume large quantities of concentrated saline solutions within minutes of presentation. This intake does not appear to be related to sodium loss or depletion because the lesioned rats are in a positive sodium balance and the appetite persists after bilateral nephrectomy. These data, in conjunction with earlier studies, suggest that the dorsomedial medulla, including the AP, acts to prevent overconsumption of water and sodium that could result in increased extracellular fluid volume.
Volume-regulatory amino acid transport in erythrocytes of the little skate, Raja erinacea
Authors: Haynes J. K. , Goldstein L.
Published: December 2017

Skate erythrocytes swell in a hypotonic medium and then reduce their volume mainly by releasing the beta-amino acids taurine and beta-alanine. Although these amino acids exhibit a net efflux, Na(+)-independent influx is also increased. Both the reduction in cell volume and increase in amino acid transport are inhibited by several inhibitors of band 3-mediated anion transport, including 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) [L. Goldstein and S. R. Brill, Am. J. Physiol. 260 (Regulatory Integrative Comp. Physiol. 29): R1014-R1020, 1991]. The objective of the present investigation was to further characterize the mechanism of volume-activated amino acid transport. Na(+)-independent amino acid uptake was studied because of the ease in controlling amino acid concentrations. Na(+)-independent taurine uptake was observed to be linear over a range of 0.1-15 mM and was not inhibited by 10 mM beta-alanine, suggesting that the transporter may be a channel rather than a carrier. The uptake of a variety of amino acids was examined to characterize the size of the putative channel. Glycine, beta-alanine, taurine, proline, gamma-aminobutyric acid (GABA), and threonine exhibited volume-activated transport that was DIDS inhibited, whereas aspartic acid, leucine, methionine, and ornithine were not transported. On the basis of the size of these amino acids, it appears that molecules containing eight or fewer major atoms and having a molecular mass of < 125-131 Da are transported during volume activation but larger molecules are not. We estimate the size of the channel to be 5.7-6.3 A in diameter.
Vasopressin, renin, and cortisol responses to hemorrhage during acute blockade of cardiac nerves in conscious dogs
Authors: O'Donnell C. P. , Keil L. C. , Thrasher T. N.
Published: December 2017

The effect of acute cardiac nerve blockade (CNB) on the increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol in response to a 30 ml/kg hemorrhage was determined in conscious dogs (n = 9). Procaine was infused into the pericardial space to produce acute reversible CNB, or saline was infused in the control hemorrhage. Blood was removed from the inferior vena cava at a rate of 1 ml.kg-1.min-1. In the control hemorrhage, plasma AVP increased from 1.8 +/- 0.3 to 219 +/- 66 pg/ml, PRA increased from 0.63 +/- 0.20 to 3.08 +/- 0.91 ng angiotensin I (ANG I).ml-1.3 h-1, and cortisol increased from 1.4 +/- 0.2 to 4.0 +/- 0.7 micrograms/dl. When the hemorrhage was repeated during acute CNB, plasma AVP increased from 2.8 +/- 1.6 to 185 +/- 59 pg/ml, PRA increased from 0.44 +/- 0.14 to 2.24 +/- 0.27 ng ANG I.ml-1.3 h-1, and cortisol increased from 1.9 +/- 0.3 to 5.4 +/- 0.6 micrograms/dl, and none of the increases differed significantly from the responses during the control hemorrhage. Left atrial pressure fell significantly after removal of 6 ml/kg of blood, but mean arterial pressure was maintained at control levels until blood loss reached 20 ml/kg during pericardial infusion of either saline or procaine. The declines in MAP at the 30 ml/kg level of hemorrhage in both treatments were similar. These results demonstrate that acutely blocking input from cardiac receptors does not reduce the increases in plasma AVP, cortisol, and PRA in response to a 30 ml/kg hemorrhage. The results of this study do not support the hypothesis that input from cardiac receptors is required for a normal AVP response to hemorrhage and suggest that other receptors, presumably arterial baroreceptors, can stimulate AVP and cortisol secretion in the absence of signals from the heart.
Glucagon and insulin regulate lipolysis in trout liver by altering phosphorylation of triacylglycerol lipase
Authors: Harmon J. S. , Rieniets L. M. , Sheridan M. A.
Published: December 2017

Rainbow trout were used to investigate the hormonal regulation by glucagon and insulin of hepatic triacylglycerol (TG) lipase activation. Two purified preparations of the trout hepatic TG lipase enzyme, the 110,000-g preparation and the resuspended ammonium sulfate fraction (ASF), were activated up to 58% with (in mM) 0.5 ATP, 0.01 cAMP, 5 MgCl2, and exogenous protein kinase over control levels. ATP or cAMP alone had no effect on activation. Activation of the trout hepatic lipase was reversible; complete inactivation of the ASF was obtained within 3 h in the presence of exogenous phosphorylase phosphatase. Adenosine 3',5'-cyclic monophosphate (cAMP)/ATP-dependent 32P-phosphorylation of trout hepatic lipase was observed within 5 min of incubation with the cAMP/ATP-Mg2+ activation system and 25 microCi [32P]ATP. Hormonal modulation of trout hepatic lipase phosphorylation was studied in isolated hepatocytes. Hepatocytes were incubated with [32P]-monopotassium phosphate for 3 h, then exposed to mammalian glucagon (GLU). Within 5 min, increased lipolysis was accompanied by a 95% increase in phosphorylation of the enzyme. Mammalian insulin (INS) depressed GLU-stimulated phosphorylation by 56% and inhibited GLU-stimulated lipolysis. These results indicate that GLU and INS modulate lipolysis in trout liver by altering phosphorylation of the TG lipase enzyme.
Somatic and visceral inputs to neurons of the rostral ventrolateral medulla
Authors: Ermirio R. , Ruggeri P. , Molinari C. , Weaver L. C.
Published: December 2017

Sympathoexcitatory neurons in the rostral ventrolateral medulla (RVLM) play an essential role in the generation of basal sympathetic tone and in the reflex regulation of blood pressure. In this study responses of RVLM "cardiovascular" neurons to somatic and visceral afferent stimulation were investigated. The activity of 34 RVLM neurons was recorded in urethan-anesthetized paralyzed and artificially ventilated rats. These neurons were identified as cardiovascular based on their baroreceptor sensitivity and their pulse-synchronous discharge. Electrical stimulation of the sciatic nerve excited 31 of the 34 RVLM units (91%). Renal nerve stimulation inhibited firing of 14 of 22 RVLM neurons tested (64%), not affecting the remaining 8 units. Stimulation of splenic nerves inhibited the discharge of 7 of 12 RVLM neurons tested (58%), whereas the remaining 5 units were not affected. All RVLM units responsive to visceral afferent stimulation were also responsive to sciatic nerve stimulation. These results indicate that RVLM cardiovascular neurons receive somatic and visceral inputs, suggesting an involvement of these units in the integration of homeostatic responses to changes in the internal and external environment.
Response of protein synthesis to anoxia and recovery in anoxia-tolerant hepatocytes
Authors: Land S. C. , Buck L. T. , Hochachka P. W.
Published: December 2017

Hepatocytes from the western painted turtle (Chrysemys picta bellii) display a profound metabolic suppression under anoxia. Fractional rates of protein synthesis fell by 92% during 12 h anoxia at 25 degrees C and were indistinguishable from the rate obtained with cycloheximide. Normoxic recovery saw protein synthesis increase to 160% of control values and return to normal after 2 h. The GTP-to-GDP ratio, implicated in the control of translation, fell threefold during anoxia. Purine nucleotide phosphate profiles suggest that this change occurs through increasing concentrations of ADP and GDP, with concentrations of ATP and GTP and total purines remaining constant. The normoxic cost for protein synthesis was calculated at 47.6 +/- 6.8 mmol ATP/g protein. Normoxic protein synthesis accounted for 36% of overall ATP turnover rates, close to the extent of O2 consumption inhibitable by cycloheximide (28%). Under anoxia, the proportion of ATP turnover utilized by protein synthesis did not change significantly. ATP turnover rates for urea synthesis reflected a similar pattern, falling 72% under anoxia. These results reflect the cell's ability to suppress protein synthesis under anoxia in a manner that is coordinated with the reduction in total metabolic rate.
Carrier-mediated transport of lactic acid in cultured neurons and astrocytes
Authors: Nedergaard M. , Goldman S. A.
Published: December 2017

The glycolytic end product lactic acid induced a rapid transient decrease in cytosolic pH in cultured neurons and astrocytes, as measured by microspectrofluorometry using the fluorescent indicator dye 2',7'-bis-(2-carboxyethyl)-5-(and-6) carboxyfluorescein acetoxymethyl ester. Over a physiological range of pH, the initial rate of cellular acidification was a saturable function of the extracellular lactate concentration, suggesting that a saturable transport system mediated lactic acid permeation across the plasma membrane. This transport process displayed stereoselectivity, with a threefold higher rate of intracellular acidification by L-lactic acid than by its D-isomer. Lactic acid-induced acidification occurred in the absence of intracellular ATP, suggesting that transport proceeded independently of the cellular energy charge. These data suggest the existence of a lactic acid carrier in mammalian neuronal and astrocytic plasma membranes, which might serve an acid-scavenging function under conditions of altered pH homeostasis. In the setting of in vivo cerebral ischemia, this carrier may promote the efflux of lactic acid from astrocytes, redistributing it among less metabolically active neurons.
GABA stimulation of gonadotropin-II release in goldfish: involvement of GABAA receptors, dopamine, and sex steroids
Authors: Trudeau V. L. , Sloley B. D. , Peter R. E.
Published: December 2017

The involvement of gamma-aminobutyric acid (GABA) in regulation of pituitary gonadotropin-II (GTH-II) release was studied in the goldfish. Intraperitoneal injection of GABA (300 micrograms/g) stimulated an increase in serum GTH-II levels at 30 min postinjection. The GABAA receptor agonist muscimol (0.1-10 micrograms/g) stimulated GTH-II in a dose-dependent manner. Baclofen, a GABAB receptor agonist, had a small but significant stimulatory effect at 1 and 10 micrograms/g; the amount of GTH-II released in response to baclofen was significantly less (P < 0.05) than that released by muscimol. Pretreatment of goldfish with bicuculline, a GABAA receptor antagonist, but not saclofen, a GABAB receptor antagonist, blocked the stimulatory effect of GABA on serum GTH-II. Elevation of brain and pituitary GABA levels with the GABA transaminase inhibitor, gamma-vinyl-GABA (GVG), decreased hypothalamic and pituitary dopamine (DA) turnover rates, indicating that GABA may stimulate GTH-II release in the goldfish by decreasing dopaminergic inhibition of GTH-II release. The release of GTH-II stimulated by muscimol and GVG was potentiated by pharmacological agents that decrease inhibitory dopaminergic tone, indicating that DA may also inhibit GABA-stimulated GTH-II release. Based on the linear 24-h accumulation of GABA in brain and pituitary after GVG injection, implantation of testosterone, estradiol, or progesterone, previously shown to regulate the serum GTH-II release response to gonadotropin-releasing hormone and GABA, was also found to modulate GABA synthesis in the brain and pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)
Impairment of insulin action on peripheral glucose uptake and hepatic glucose production in tumor-bearing rats
Authors: Lang C. H. , Skrepnik N. , Dobrescu C. , Burns A. H.
Published: December 2017

The present study was performed to determine the time-course for the development of peripheral and hepatic insulin resistance in rats as a result of an increasing tumor burden. Animals were inoculated with Yoshida ascites hepatoma, and studies were conducted during the early phase of tumor growth (day 4) at which time there was no change in food intake and at a later time point (day 8) when the tumor burden was increased and rats demonstrated anorexia. In vivo insulin action was accessed under euglycemic hyperinsulinemic conditions, in which insulin was infused at rates sufficient to produce arterial insulin levels that represent high physiological (3.5 ng/ml) or maximally stimulating values (180 ng/ml). On day 4, tumor-bearing (TB) rats were euglycemic, and whole body glucose turnover was elevated 32%. Insulin-mediated glucose uptake (IMGU) in TB rats was similar to control values at the low insulin infusion rate but reduced by 53% under maximally stimulating conditions. The insulin-induced suppression of glucose production was similar in TB and control animals at this time point. In contrast, on day 8, TB rats were hypoglycemic and glucose turnover was reduced 35%. The impairment in IMGU was more severe than seen earlier, with glucose uptake being reduced 39 and 61% at both levels of hyperinsulinemia. At this time point, the ability of insulin to inhibit glucose production was also impaired. These results indicate that the insulin resistance induced by the Yoshida hepatoma was manifested initially by a reduction in IMGU by peripheral tissues. As the tumor burden increased peripheral insulin resistance became more severe and an impairment in hepatic insulin action was observed.
Energy balance in pregnant hamsters: a role for voluntary exercise?
Authors: Bhatia A. J. , Wade G. N.
Published: December 2017

During pregnancy or after experimental manipulations of ovarian hormone levels, Syrian hamsters exhibit changes in energy balance and body fat content without modifying their food intake. The present experiments determined whether fluctuations in voluntary exercise play a role in these changes in energy balance, as they appear to do in other species. As expected, pregnant hamsters maintained a constant level of food intake and lost approximately 40% of their body fat. These animals did not show the abrupt decrease in activity after mating that is seen in rats. Instead, they maintained their high, premating level of running wheel activity until the last 3 days of pregnancy. Similarly, ovariectomy and replacement therapy with estradiol or estradiol+progesterone caused substantial changes in energy balance in the absence of significant changes in food intake or running wheel activity. These findings indicate that, unlike rats, Syrian hamsters do not exhibit substantial changes in voluntary exercise during pregnancy or in response to manipulations of ovarian steroid levels. Therefore, neither changes in food intake nor in voluntary exercise play any important role in the pregnancy- or steroid-induced changes in energy balance in Syrian hamsters.
Unaltered cerebral blood flow during hypoglycemic activation of the sympathochromaffin system in humans
Authors: Powers W. J. , Boyle P. J. , Hirsch I. B. , Cryer P. E.
Published: December 2017

To determine if increases in plasma epinephrine and norepinephrine caused by hypoglycemia are associated with increments in cerebral blood flow (CBF), we measured CBF with positron emission tomography in normal humans at ambient fasting arterial plasma glucose levels and at clamped plasma glucose levels of 5.3, 3.5, and 2.8 mmol/l using the hyperinsulinemic, stepped hypoglycemic clamp technique. Despite significant increases in plasma epinephrine to 7,340 +/- 350 (SE) pmol/l and in plasma norepinephrine to 3.32 +/- 0.35 nmol/l, mean hemispheric CBF (41 +/- 1, 49 +/- 1, 48 +/- 2, and 51 +/- 3 ml x 100 g-1 x min-1) remained constant at the ambient (5.2), 5.3, 3.5, and 2.8 mmol/l glycemic levels, respectively. Furthermore, there was no correlation between CBF and either plasma epinephrine levels ranging from 160 to 10,580 pmol/l or plasma norepinephrine levels ranging from 0.56 to 5.10 nmol/l. Failure to demonstrate any dose-response relationship between plasma catecholamine levels and CBF argues against their primary role in cerebrovascular control during hypoglycemia.
Anoxic suppression of Na(+)-K(+)-ATPase and constant membrane potential in hepatocytes: support for channel arrest
Authors: Buck L. T. , Hochachka P. W.
Published: December 2017

The maintenance of ion gradients across the plasma membrane by the Na(+)-K(+)-ATPase has been shown to utilize a large fraction of the total cellular energy demand. In view of the importance of ion gradients to cellular function, and the remarkable anoxia tolerance of Chrysemys picta bellii (western painted turtle) and hepatocytes isolated from this species, it was of interest to determine if in response to anoxia 1) ion gradients were maintained and 2) if the activity of the plasma membrane Na(+)-K(+)-ATPase changed to aid in ion gradient maintenance. From normoxic hepatocyte suspensions the ouabain-inhibitable 86Rb+ uptake (a measure of Na(+)-K(+)-ATPase activity) was determined, and the rate of ATP utilization was 19.1 mumol ATP.g cells-1.h-1 or 28% of the total normoxic cellular ATP turnover. In response to anoxic incubation the activity of the pump decreased by 75% to 4.8 mumol ATP.g cells-1.h-1 and this comprised 74% of the total anoxic ATP turnover. Presently, it is not known whether the observed reduction in Na(+)-K(+)-ATPase activity is regulated by 1) allosteric modification, 2) endocytosis from the membrane, or 3) reduced Na+ influx. Plasma membrane potential was measured during anoxia, using the distribution of 36Cl-, and was not significantly different from the normoxic measurement, -30.6 +/- 3.9 and -31.3 +/- 5.8 mV, respectively. Therefore, the plasma membrane ion gradient is maintained during anoxia, and since the activity of the Na(+)-K(+)-ATPase decreases, the influx of ions must also decrease.(ABSTRACT TRUNCATED AT 250 WORDS)