bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid changes in metabolic cold defense and GDP binding to brown adipose tissue mitochondria of rat pups
Authors: Kortner G. , Schildhauer K. , Petrova O. , Schmidt I.
Published: December 2017

To determine developmental changes of brown adipose tissue (BAT) thermogenic activity at defined circadian and thermal states, we evaluated the time course of cold-induced increases of in vitro guanosine 5'-diphosphate (GDP) binding in parallel with whole body metabolism (oxygen consumption, VO2) and core temperature (Tc) in 1- to 11-day-old rat pups. During the maximum phase of the juvenile diurnal cycle, Tc of littermates was recorded continuously and VO2 alternately until 2 min before animals were killed for removal of interscapular BAT. GDP binding after 1.5 h at thermoneutrality and its increase during physiologically comparable cold loads were significantly lower in 1-day-old pups than in 5- and 11-day-old pups. Cold defense was activated more rapidly in the older pups, but GDP binding in even the 1-day-old pups was significantly increased during the second 10-min period of cold exposure. We conclude that rapid changes in thermogenic activity, in connection with the known developmental changes in the dependence of the suckling rat's metabolic cold defense on maternal and sibling contact and circadian phase, will distort longitudinal studies of any fast-changing BAT parameter when the conditions immediately before tissue removal are not thoroughly controlled.
The 10-Hz sympathetic rhythm is dependent on raphe and rostral ventrolateral medullary neurons
Authors: Zhong S. , Huang Z. S. , Gebber G. L. , Barman S. M.
Published: December 2017

We studied the effects of brain stem and spinal lesions on the 10-Hz rhythms in left and right inferior cardiac sympathetic nerve discharge (SND) of baroreceptor-denervated, decerebrate cats. Unilateral medullary lesions [parasagittal section 1.5 mm lateral to midline, radiofrequency lesion of the rostral ventrolateral medulla (RVLM), or chemical inactivation (muscimol) of the RVLM] dramatically reduced the 10-Hz rhythmic discharges in the two nerves. Power in the 10-Hz band of ipsilateral inferior cardiac SND was reduced more than that in contralateral SND. In contrast, bilateral parasagittal medullary sections or microinjection of muscimol into the medullary raphe uniformly reduced the 10-Hz rhythmic discharges of both nerves. Unlike unilateral medullary lesions, rostral pontine or cervical spinal hemisection reduced the 10-Hz discharges of only the ipsilateral inferior cardiac nerve. The chemical inactivation experiments demonstrate that the 10-Hz rhythm in SND is dependent on medullary raphe and RVLM neurons. Moreover the experiments with unilateral lesions demonstrate a mutually facilitatory interaction of medullary circuits that are responsible for the 10-Hz rhythmic discharges in sympathetic nerves located on opposite sides of the body.
Intracellular compartmentation of organic anions within renal cells
Authors: Miller D. S. , Stewart D. E. , Pritchard J. B.
Published: December 2017

Epifluorescence microscopy and video-image analysis were used to measure the distribution of the monovalent organic anion fluorescein (FL) within the cells of three organic anion-secreting renal epithelia: crab urinary bladder (a proximal tubule analogue), opossum kidney (OK) cells in culture, and intact teleost proximal tubules. In all three preparations the intracellular FL distribution was nonuniform. Two distinct intracellular compartments were detected, one being diffuse and cytoplasmic and the other punctate. With low FL concentrations in the medium (1 microM and below) dye accumulation in the punctate compartment exceeded that of the cytoplasm. In crab bladder epithelium FL uptake into both compartments was inhibited by external probenecid, p-aminohippurate (PAH), and LiCl and stimulated by 10-50 microM external glutarate, suggesting that the punctate compartment loaded by a two-step mechanism: transport into the cytoplasm at the basolateral membrane, followed by accumulation at specific intracellular sites. Experiments in which FL was microinjected into OK cells directly demonstrated movement of FL from the cytoplasmic to the punctate compartment. Accumulation in the latter was specific, i.e., inhibitable by coinjected PAH and probenecid, and energy dependent. Together, these findings indicate that during secretion organic anions are sequestered within renal cells. The role of sequestration in overall transport remains to be determined.
Electrophysiology and neuropharmacology of noradrenergic projections to rat PVN magnocellular neurons
Authors: Saphier D.
Published: December 2017

Responses of electrophysiologically identified tuberohypophysial paraventricular nucleus (PVN) neurons were examined following electrical stimulation of the A1, A2, A6, and C2 catecholaminergic cell groups and of the ventral noradrenergic ascending bundle (VNAB). A1, A2, and A6 stimulation evoked primarily excitatory responses from the cells recorded, but C2 stimulation yielded a greater proportion of inhibitory responses. VNAB stimulation at low frequencies (0.5/5 Hz) excited the majority of cells tested, but high-frequency (50 Hz) trains of stimulation reversed the direction of response to inhibition for approximately half of the cells excited by single-shock stimulation. Only 5-Hz stimulation had any affect on blood pressure, causing a slight increase. Treatment with alpha-methylparatyrosine, to inhibit (nor) epinephrine synthesis, reduced the proportion of excitatory responses and prevented the response reversals following 50-Hz VNAB stimulation. Treatment with 6-hydroxydopamine also reduced the proportion of cells excited by VNAB stimulation. Iontophoresis of either norepinephrine or the alpha 1-adrenoceptor agonist l-phenylephrine increased the activity of most cells tested whilst the alpha 1-antagonist ergotamine reduced the activity of most cells tested and prevented excitation elicited by VNAB stimulation. The alpha 2-agonist clonidine excited all cells tested. The beta-antagonist propranolol increased the activity of the majority of cells and prevented inhibitory responses following 50-Hz VNAB stimulation. The results confirm a role for brain stem projections in regulating PVN neuronal activity and demonstrate for the first time that the VNAB provides excitatory input to the PVN, primarily regulated by alpha 1-adrenoceptors. The effects of propranolol on spontaneous activity, and on the inhibitory responses following high-frequency VNAB stimulation, indicate the presence of an inhibitory counterbalancing beta-adrenoceptor mechanism.
Modulation of tissue-type plasminogen activator by retinoids in rat plasma and tissues
Authors: Van Bennekum A. M. , Emeis J. J. , Kooistra T. , Hendriks H. F.
Published: December 2017

In this study the effect of vitamin A status and retinoid treatment on the activity of tissue-type plasminogen activator (TPA) and its inhibitor, plasminogen activator inhibitor-type 1 (PAI-1), in plasma and in several tissues was investigated in BN/BiRij rats. Hypervitaminosis A and retinoic acid treatment increased plasma TPA activity by approximately 50%, but PAI-1 activity was not affected. The effect of retinyl palmitate treatment on plasma TPA activity was already significant after 5 days and continued for at least up to 8 wk. Isotretinoin treatment affected neither plasma TPA nor PAI-1 activity. In plasma of vitamin A-deficient rats, TPA activity was decreased by a factor of three, whereas PAI-1 activity was increased twofold. Modulation of plasma TPA activity by vitamin A status and retinoic acid treatment was associated with similar changes in tissue TPA activity. This suggests that the changes in plasma TPA activities might be the result of changes in tissue TPA synthesis.
Attenuated glomerular cGMP production and renal vasodilation in streptozotocin-induced diabetic rats
Authors: Wang Y. X. , Brooks D. P. , Edwards R. M.
Published: December 2017

Because diabetes is associated with impaired vascular endothelium, we have investigated endothelium-dependent cGMP stimulation in isolated glomeruli and renal vasodilation in normal and diabetes mellitus (DM) rats. Rats treated with streptozotocin (60 mg/kg iv) developed high blood glucose, polyuria, enlarged kidneys, and slow weight gain compared with control animals. Chronic treatment with insulin reversed these changes. In isolated glomeruli, the endothelium-dependent vasodilator, acetylcholine (ACh), stimulated cGMP accumulation concentration dependently; however, the response was significantly attenuated in glomeruli from DM rats when compared with normal rats or DM rats treated with insulin. Sodium nitroprusside-induced cGMP accumulation was also slightly but significantly reduced in glomeruli from DM rats, however, the response to atriopeptin III was unaltered. In rats, intravenous infusion of ACh (1 and 10 micrograms.kg-1.min-1) moderately decreased blood pressure and increased renal blood flow without a significant change in glomerular filtration rate. The renal vasodilatory response to ACh was significantly diminished in DM rats, but not in DM rats treated with insulin. Acute treatment with insulin did not restore the ACh response, although the blood glucose level was normalized. We conclude that there is a reduced renal vasodilatory response observed in DM, and this is due to an impairment of the renal vascular endothelium to produce endothelium-dependent relaxation factor (nitric oxide) and/or a defective soluble guanylate cyclase.
Suppression of sham feeding by intraintestinal nutrients is not correlated with plasma cholecystokinin elevation
Authors: Brenner L. , Yox D. P. , Ritter R. C.
Published: December 2017

To test the possibility that blood-borne cholecystokinin (CCK) participates in suppression of sham feeding by intestinal nutrients in rats, we examined the ability of oleate, maltose, L-phenylalanine (L-Phe), and casein to suppress sham ingestion of 15% sucrose solution. Plasma CCK concentrations were measured in parallel experiments in which the same intestinal nutrients were infused in rats that were not feeding. Intraintestinal oleate suppressed sham feeding and elevated plasma CCK concentrations. Casein infusion produced plasma CCK concentrations similar to those produced by oleate but did not suppress sham feeding. Both maltose and L-Phe suppressed sham feeding but failed to significantly elevate plasma CCK. Previously we demonstrated that CCK receptor antagonists attenuate suppression of sham feeding by intestinal infusion of either oleate or maltose, suggesting that endogenous CCK participates in suppression of sham feeding by some intestinal nutrients. The results of the study reported here suggest that plasma CCK levels after nutrient infusion are not correlated with suppression of sham feeding. Therefore, the mechanism of CCK's participation in nutrient-induced suppression of sham feeding may not depend on stimulus-induced elevation of plasma CCK.
Influence of endotoxin on nocturnal sleep in humans
Authors: Pollmacher T. , Schreiber W. , Gudewill S. , Vedder H. , Fassbender K. , Wiedemann K. , Trachsel L. , Galanos C. , Holsboer F.
Published: December 2017

Sleepiness is a common complaint during infectious diseases, but the interaction between sleep and host defense mechanisms has been poorly explored in humans. We therefore studied the effect of endotoxin, a major pathophysiological factor in gram-negative bacterial infections, on sleep and on parameters of the primary host response in men. In a single-blind counterbalanced trial, 15 healthy volunteers received either placebo or Salmonella abortus equi endotoxin (0.4 ng/kg body wt) intravenously on two separate occasions. Nocturnal sleep was recorded, and rectal temperature and the plasma levels of tumor necrosis factor-alpha, interleukin-6, adrenocorticotropic hormone, and cortisol were monitored for 12 h. Endotoxin reduced the relative amounts of wakefulness (P < 0.05) and rapid-eye-movement (REM) sleep (P < 0.05) and increased the relative amount of non-REM sleep (P < 0.01). Electroencephalogram delta power during non-REM sleep, as measured by spectral analysis, was not altered by endotoxin. The endotoxin-induced changes in sleep structure were related temporally and quantitatively to the increases in rectal temperature and to the release of cytokines and neurohormones. It is concluded that cytokines and neurohormones mediate the effects of endotoxin upon sleep. The ensuing increase in non-REM sleep may be part of the adaptive host response to bacterial infections in humans.
Adrenal medulla as a mediator of diet-induced hypertension
Authors: Kaufman L. N. , Li H. Y. , Peterson M. M. , Gilardy A. K.
Published: December 2017

Male Sprague-Dawley rats fed either a high-fat or glucose-enriched diet for 10 wk developed higher blood pressure (BP) and higher urinary catecholamine excretion than rats fed a control diet. After 10 wk of diet treatment, systolic BP was 164 +/- 3, 156 +/- 2, and 145 +/- 4 mmHg in rats fed the high-fat, glucose, and control diets, respectively (P < 0.02 vs. control). During weeks 7-9 of diet treatment, excretion of epinephrine and norepinephrine was increased in hypertensive rats (those fed the high-fat or glucose diet) when compared with rats fed the control diet (P < 0.001). The purpose of this study was to determine whether the hypertensive response to nutrients could be prevented by prior surgical removal of the adrenal medulla. Adrenal demedullation nearly abolished epinephrine excretion, attenuated norepinephrine excretion, and completely blocked the hypertensive response to dietary fat and glucose. These findings suggest that adrenal medullary catecholamines play a role in the hypertensive response to nutrients.
Meal-induced c-fos expression in brain stem is not dependent on cholecystokinin release
Authors: Fraser K. A. , Davison J. S.
Published: December 2017

Sprague-Dawley rats injected with a "physiological" dose of cholecystokinin octapeptide (CCK-8; 6 micrograms/kg ip) expressed c-fos immunoreactivity in the nucleus of the tractus solitarius (NTS) and the area postrema (AP) of the brain stem. Injection of the CCK-A antagonist L-364,718 30 min before CCK-8 injection eliminated c-fos expression in these regions. These findings support the hypothesis that CCK-8 induced c-fos expression is mediated by CCK-A receptors. We then tested whether a meal (Isocal) could activate c-fos, and, if so, whether this response could be eliminated by L-364,718. Ingestion of Isocal induced c-fos immunoreactivity in the NTS and AP. Meal-induced c-fos expression was not blocked by the CCK-A antagonist L-364,718. These findings demonstrate for the first time that a purely physiological nonnoxious stimulus, a meal, induces c-fos in the rat brain stem and indicate that feeding induces c-fos expression by a pathway that is largely, if not entirely, independent of CCK release.
Angiotensin-converting enzyme inhibition and Na appetite: microbehavioral analysis and nycthemeral physiology
Authors: Rowland N. E. , Nicholson T. M. , Smith J. C.
Published: December 2017

The present experiments describe a marked nycthemeral rhythm in both the appetite for 0.3 M NaCl solution and components of the renin-angiotensin-aldosterone axis stimulated in Sprague-Dawley rats by chronic administration of enalapril, an angiotensin I-converting enzyme inhibitor. Continuous recording of water, NaCl, and food intakes shows that the sodium appetite is manifest as discrete bouts of salt ingestion in temporal proximity to meals and is partially independent of water bouts. In particular, salt bouts occur without water bouts in the late afternoon of a 12:12-h light-dark cycle and continue periprandially with water bouts during the night. Intake of all three commodities is minimal in the morning. In a second experiment, it was determined that plasma renin activity (PRA) was maximally elevated by chronic enalapril in the daytime and that plasma aldosterone was reduced by enalapril but continued to show nycthemeral rhythm peaking in the afternoon. The concurrent maxima in PRA and aldosterone in the afternoon in enalapril-treated rats thus coincides with NaCl intake in the absence of water intake.
Endothelin-induced natriuresis and diuresis are pressure-dependent events in the rat
Authors: Uzuner K. , Banks R. O.
Published: December 2017

The goal of the current study was to determine the mechanism by which doses of endothelin (ET) that do not markedly affect the glomerular filtration rate (GFR) cause a natriuresis and diuresis. ET was infused into pentobarbital-anesthetized female rats at 50 ng.kg-1.min-1 iv for 30 min. In controls (n = 6 rats; n = 5 in all other groups), ET increased mean arterial blood pressure (MAP) from 95 +/- 2 to 131 +/- 2 (SE) mmHg, Na excretion (UNa V) from 0.34 +/- 0.07 to 1.83 +/- 0.2 meq/min, and urine flow rate (V) from 13 +/- 1 to 24 +/- 3 ml/min (all P < 0.01 vs. baseline). At 15 min during infusion of ET, the GFR was not affected (2.1 +/- 0.1 to 2.2 +/- 0.1 ml/min) but modestly decreased to 1.8 +/- 0.1 ml/min at 30 min (P < 0.05 vs. baseline). Either removing the capsule from both kidneys during surgery or maintaining renal arterial pressure at baseline values with an adjustable clamp on the aorta above the right renal artery abolished the ET-induced increase in UNa V and V. Meclofenamate also did not alter the ET-induced increase in MAP, V, or UNa V. To determine the intrarenal site of action of ET, experiments were conducted with ET plus amiloride or with a combination of amiloride plus furosemide; there was a larger ET-induced diuresis and natriuresis in amiloride-treated rats and an even larger response with amiloride plus furosemide compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of brain calcium channels by plasma proteins from anoxic turtles
Authors: Bickler P. E. , Gallego S. M.
Published: December 2017

Recent studies suggest that turtles avoid disturbances in brain ionic regulation during anoxia by reducing the activity of brain calcium and sodium channels. Because glutamate released during anoxia may cause cytotoxic elevations in intracellular calcium, blockade of glutamate-mediated calcium channels may be essential for cellular survival. Elevations in intracellular calcium, measured with the fluorescent dye fura 2, were used to assay glutamate-induced activation of calcium channels in cerebrocortical brain slices from rats and turtles. Fourteen hours of anoxia produced long-lasting reduction in glutamate-mediated calcium flux in the turtle brain. Furthermore, a plasma protein from turtles maintained under anoxic conditions produced blockade of glutamate-mediated calcium flux in cortical brain slices from both turtles and rats. These results suggest that long-lasting modulation of brain calcium channels as well as blockade of calcium channel activity by regulatory proteins may play important roles in reducing transcellular ion fluxes in turtles during anoxia.
Subfornical organ efferents to paraventricular nucleus utilize angiotensin as a neurotransmitter
Authors: Li Z. , Ferguson A. V.
Published: December 2017

In this study, we have utilized electrophysiological single unit recordings to evaluate the effects of nonpeptidergic angiotensin II (ANG II) antagonists on neural responses of hypothalamic paraventricular nucleus (PVN) neurons to either electrical stimulation in subfornical organ (SFO) or direct application of ANG II. Electrical stimulation (200-400 microA; 0.1 ms) in the SFO resulted in excitatory responses in 36 of 50 PVN neurons tested. Peristimulus histogram analysis of such excitatory effects demonstrated latencies of < 30 ms and variability of response times of approximately 50 ms in 14 of these 36 neurons. In view of previous anatomic and electrophysiological studies such inputs were therefore considered to be monosynaptically mediated by direct neural inputs from the SFO. The remaining 22 cells excited by such SFO stimulation showed responses of longer latency and duration suggestive of a different underlying synaptic mechanism. Local pressure ejection of ANG II into the PVN resulted in increased neural activity in 50% (9 of 18) of the neurons tested. After systemic (3 mg/kg iv) or local (2 x 10(-2) M; 1-25 s; 2-40 psi) microinjection of the nonpeptidergic angiotensin II1 (AT1) receptor antagonist losartan, SFO excitations were attenuated in 63.9% (23 of 36) of the PVN neurons tested, such pharmacologically blocked excitatory responses being reduced by 68.3 +/- 5.2% from control stimulation effects (P < 0.001). Similar losartan-induced attenuations of both short latency (presumed monosynaptic) (50.0%) and longer latency (72.7%) responses were observed. In addition, losartan also abolished the excitatory effects of local administration of ANG II on 77.8% (7 of 9) of ANG II-sensitive neurons in PVN tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of extent of muscle shortening and heart rate on work from frog heart trabeculae
Authors: Syme D. A.
Published: December 2017

Shortening, lengthening, and net work done by frog (Rana pipiens) heart trabeculae were measured over a range of strain amplitudes (length change) and cycle frequencies. Net work, the product of muscle strain and force over a full lengthening/shortening cycle, increased with strain to strains well over 25% of the muscle's rest length, a value greater than optimum strains reported for most skeletal muscles. A distinct optimum strain for net work was not found. Maximum net work per cycle averaged 7.5 J/kg for ventricular muscle and 2.0 J/kg for atrial muscle. Isometric twitch stress was maximal at 0.4-0.6 Hz twitch frequency in ventricular trabeculae (average 51 kN/m2) and 0.6-1.4 Hz in the atrium (average 14 kN/m2). The twitch duration decreased with increasing twitch frequency. Shortening and net work were maximal at 0.7-Hz cycle frequency in ventricular trabeculae and 0.9 to 1.4 Hz in the atrium. The decline in work per cycle at slower frequencies was due in part to a decline in twitch force. Maximum power for the ventricle was approximately 5 W/kg and occurred at 0.8 Hz and 26% strain, and was 1/3 to 1/4 the power of most skeletal muscles studied at similar temperatures.
Effect of exercise training on RSNA, baroreflex control, and blood pressure responsiveness
Authors: Negrao C. E. , Irigoyen M. C. , Moreira E. D. , Brum P. C. , Freire P. M. , Krieger E. M.
Published: December 2017

The effect of exercise training (ET) on renal sympathetic nerve activity (RSNA), baroreflex control of RSNA and heart rate (HR), and arterial pressure (AP) responsiveness to phenylephrine and angiotensin II (ANG II) was studied in six trained (T) and six sedentary (S) male Wistar rats. ET was performed on a motor treadmill for 13 wk. The RSNA signals of unanesthetized rats were processed by an analog-to-digital converter to quantify the nerve discharges associated with changes in AP and HR. The reflex control of RSNA and HR were evaluated during progressive injections of phenylephrine and sodium nitroprusside. Mean arterial pressure (MAP) was similar in both groups. RSNA was significantly lower in T rats (28 +/- 2 vs. 36 +/- 3%). T rats had an impairment of baroreflex control of RSNA in response to nitroprusside (4.9 +/- 0.89 vs. 12.3 +/- 1.2 bars.cycle-1.mmHg-1). ET decreased AP responsiveness for phenylephrine and ANG II. Therefore ET produces 1) no change in resting MAP but a significant decrease in RSNA and AP responsiveness and 2) partial impairment of baroreflexes, i.e., bradycardic responses and RSNA during MAP decrease.
Role of intrarenal ANG II in reflex neural stimulation of plasma renin activity and renal sodium reabsorption
Authors: Nelson L. D. , Osborn J. L.
Published: December 2017

Renal sympathetic stimulation of plasma renin activity (PRA) and sodium reabsorption was examined in conscious dogs before and during intrarenal angiotensin II (ANG II)-type 1 receptor blockade with losartan (Dup-753) and converting enzyme inhibition. In uninephrectomized dogs, renal function and PRA responses to 14% blood volume depletion (BVD) were measured. BVD was utilized to activate renal sympathetic outflow in the absence of hypotension. In eight vehicle-treated dogs, 14% BVD increased PRA from 1.38 +/- 0.32 to 2.79 +/- 0.66 ng ANG I.ml-1 x h-1 and decreased urinary sodium excretion (UNaV) from 85.1 +/- 11.3 to 45.4 +/- 7.5 mueq/min. During losartan (n = 6) and captopril (n = 5) infusion, plasma renin responses were enhanced in response to 14% BVD (1.93 +/- 0.48 to 5.74 +/- 2.25 and 3.03 +/- 0.73 to 9.19 +/- 1.94 ng ANG I.ml-1 x h-1, respectively), whereas antinatriuretic responses were similar to vehicle-infused dogs. Thus, neurogenic antinatriuresis is not mediated by secondary generation of ANG II, since UNaV decreased similarly to control in all conditions of ANG II blockade. Tonic intrarenal and/or circulating ANG II synthesis of dogs on a normal sodium diet inhibit neurogenic stimulation of renin release, since PRA responses were enhanced after blockade of ANG II.
Serum immunoreactive erythropoietin and red blood cell mass during pregnancy in conscious rats
Authors: Del Valle G. O. , Mosher M. D. , Conrad K. P.
Published: December 2017

Serum erythropoietin concentration increases during human pregnancy and presumably accounts for expansion of red blood cell mass. The mechanism(s) underlying gestational changes of serum erythropoietin are unknown. Moreover, if erythropoietin synthesis increases, then the organ(s) questions about erythropoietin in pregnancy, we first set out to establish an animal model. Chronically instrumented, conscious unrestrained rats were studied. 51Cr-labeled red blood cells and radioimmunoassay were used to assess red blood cell mass and serum erythropoietin, respectively. Except for a lower hematocrit (P < 0.05 vs. virgin rats) and a slightly higher plasma volume (P value not significant) for gravid rats on gestational day 6, all other variables measured in early pregnancy rats were comparable to those measured in virgin control animals. Significant increases in total blood volume, plasma volume, and red blood cell mass were observed by gestational day 13 (midpregnancy) when compared with virgin control rats. These changes were even more pronounced on gestational day 20. Serum immunoreactive erythropoietin was also significantly increased at both of these stages of pregnancy. We conclude that the gravid rat is a reliable animal model of human gestation in which to further investigate erythropoietin in pregnancy.
Role of decreased plasma volume in hematocrit alterations during incremental treadmill exercise in horses
Authors: McKeever K. H. , Hinchcliff K. W. , Reed S. M. , Robertson J. T.
Published: December 2017

Six intact (IN) and six splenectomized (SP) mares were subjected to an incremental exercise test to examine the role of decreases in plasma volume (PV) in the changes in hematocrit (Hct) normally seen with exercise. Each horse underwent an incremental exercise test in which it ran on a treadmill up a fixed incline of 6 degrees. The test started at a speed of 4 m/s, and speed was increased 1 m/s each min until heart rate reached a plateau. Blood samples were obtained at rest and at the end of the 4, 5, 6, and 7 m/s steps of the exercise test. Resting PV was greater (P < 0.05) in the IN group (28.6 +/- 0.5 liters) compared with SP horses (22.7 +/- 2.2 liters). Exercise produced a significant increase in Hct in both groups of horses; however, the increases were greater (P < 0.05) at all exercise intensities in IN compared with SP horses. Hct increased rapidly during the first step (4 m/s) in the exercise test in the IN animals. After this, Hct increased slowly in IN horses, and values for the 5, 6, and 7 m/s steps paralleled the changes observed in the SP horses. Corrected Hct values were then used to calculate the relative change in PV. Exercise produced a significant decrease in PV in both groups of horses; however, there were no differences (P > 0.05) between the groups when IN horses (-13 +/- 3 and -18 +/- 2%) were compared with SP horses (-14 +/- 4 and -17 +/- 4%) at the 6 and 7 m/s steps of the exercise test.(ABSTRACT TRUNCATED AT 250 WORDS)
Selective retention of essential fatty acids: the role of hepatic monoacylglycerol acyltransferase
Authors: Xia T. , Mostafa N. , Bhat B. G. , Florant G. L. , Coleman R. A.
Published: December 2017

In the suckling rat, chick embryo, and hibernating marmot, fatty acids provide the major source of energy, and despite the high rate of hepatic beta-oxidation, these animals selectively retain long-chain polyunsaturated derivatives of C18:2n-6 and C18:3n-3. To determine whether the hepatic microsomal activity monoacylglycerol acyltransferase (MGAT) (EC 2.3.1.22) could provide a mechanism to selectively acylate monoacylglycerols that contain essential fatty acids, we tested the ability of MGAT activity from each of the three species to acylate sn-2-monoC18:1-, sn-2-monoC18:2-, sn-2-monoC18:3-, and sn-2-monoC20:4-glycerols. Hepatic MGAT activity acylated sn-2-monoC18:3-glycerol and sn-2-monoC18:2-glycerol in preference to sn-2-monoC18:1-glycerol in each of the three different lipolytic animals. MGAT's acyl group specificity could not be explained by invoking differences in membrane fluidity because the apparent affinity for sn-2-monoC20:4-glycerol was not increased. Further, sn-2-monoC18:3-glycerol remained a preferred substrate under assay conditions when both the C18:3 and C18:1 species were present in equal amounts. As would be predicted in the presence of high activity of a selective MGAT, the hepatic glycerolipids from neonatal rats showed increases in dienoic, trienoic, and C22:6 fatty acids and relative decreases in monoenoic, saturated, and C20:4 fatty acids. We hypothesize that, during lipolysis, the reacylation of sn-2-monoacylglycerols by MGAT may provide a mechanism by which essential fatty acids are retained within specific tissues.
Gastric vagus mediates immobilization-induced hypocalcemia in rats
Authors: Ma J. , Aou S. , Matsui H. , Hori T.
Published: December 2017

The involvement of the parasympathetic nervous system in the etiology of stress-induced hypocalcemia was investigated in the rat. Atropine methyl bromide (0.1 and 0.6 mg/kg ip) given 20 min before immobilization (IMB) was observed to suppress the induction of hypocalcemia in a dose-dependent manner. A vagotomy of the bilateral cervical trunks also abolished the IMB-induced hypocalcemia. A vagotomy on either the thyroid/parathyroid branches or the celiac branches had no effect on the IMB-induced hypocalcemia, but a vagotomy on the gastric branches completely abolished it. Pretreatment with either secretin (2 and 6 micrograms/kg ip), an inhibitor of gastrin release, or cimetidine (5 and 10 mg/kg ip), a histamine H2-receptor antagonist, diminished the IMB-induced hypocalcemia. The concentration of serum gastrin increased significantly during IMB. It is thus concluded that the decreased levels of plasma calcium caused by IMB are due to the activation of the vagus innervating the stomach. Gastrin and histamine are also involved as a consequence of the activation of the vagus.
Brain lactate and pH dissociation in edema: 1H- and 31P-NMR in collagenase-induced hemorrhage in rats
Authors: Mun-Bryce S. , Kroh F. O. , White J. , Rosenberg G. A.
Published: December 2017

Brain edema has been shown to increase brain lactate, but the effect on pH is unclear. We used in vivo nuclear magnetic resonance (NMR) spectroscopy to measure lactate and pH in a region of brain edema. Ninety-five anesthetized rats underwent proton and 31P-NMR spectroscopy with a 7-T 89-mm vertical bore spectrometer, using a surface coil over the edematous regions and distant from a hemorrhage produced by the injection of bacterial collagenase. Brain water content was measured from multiple regions after the NMR measurements in all rats. Lactate was significantly increased 4 h after the hemorrhage and remained elevated for 48 h, but brain pH was unaffected. The increase in lactate correlated (P < 0.01) with the increase in water content in the measured region. We conclude that lactate and pH are dissociated in a region of primarily vasogenic edema.
Role of excitatory amino acids in regulation of rat pial microvasculature
Authors: Huang Q. F. , Gebrewold A. , Zhang A. , Altura B. T. , Altura B. M.
Published: December 2017

Recently, attention has been drawn to the possibility that excitatory amino acids (EAAs) may play an important role in the pathogenesis of hypoxic-ischemic neuronal injury. Exaggerated release of EAAs and excessive stimulation of N-methyl-D-aspartate (NMDA) receptors and other EAA receptors have been suggested to contribute to neuronal death in ischemia and anoxia. A number of in vitro and in vivo experimental studies have shown that EAA-receptor antagonists exert a protective effect on the brain after cerebral ischemia. Because neurons are in close apposition to small intracerebral vessels, synaptically released EAAs might also regulate small blood vessel function. With the use of quantitative television microscopic observations, in vivo studies were undertaken on pial arterioles of rats. Perivascular administration of cumulative doses (10(-7)-10(-2) M) of L-glycine, L-glutamate, L-aspartate, and NMDA on the pial microvessels resulted in concentration-dependent constriction of pial arterioles (5-30% decreases in diameter) and cerebrovasospasm; the relative order of potency was aspartate > NMDA > glycine > glutamate. High concentrations of EAAs often resulted in rupture of postcapillary venules. No amine or opiate antagonist or cyclooxygenase inhibitor prevented or attenuated the effects of these putative EAAs. EAA-induced constriction and spasm of pial arterioles as well as rupture of venules could, however, be blocked by the noncompetitive NMDA-receptor antagonist MK-801 and by Mg2+. MK-801 also produced a concentration-dependent relaxation on normal pial arterioles. These results are compatible with the idea that a specific NMDA-receptor complex (RC) exists in rat cortical microvessels, which subserves vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
On the fractal nature of heart rate variability in humans: effects of data length and beta-adrenergic blockade
Authors: Yamamoto Y. , Hughson R. L.
Published: December 2017

In the present study, we reinvestigated the question of whether human heart rate variability (HRV) is fractal in nature. Ten healthy volunteers participated in either of two studies conducted while beat-by-beat long-term HRV (8,500 heartbeats) was recorded for 2-3 h in the quiet, awake state in the supine position. In the first study, five subjects were tested four times each to evaluate the basic fractal nature of human HRV. The other five subjects were examined for the effects of oral propranolol (2 x 80 mg/day) on the fractal property of HRV in the second study. HRV data were analyzed by coarse-graining spectral analysis to break down their total power into harmonic and nonharmonic (fractal) components. The harmonic component was further divided into low (0.0-0.15 Hz; LF)- and high (> 0.15 Hz; HF)-frequency components. From these spectral components, %Fractal, %LF, and %HF as functions of total power were calculated. The fractal component was used to calculate the spectral exponent, beta. The %Fractal of human resting HRV was 85.5 +/- 4.4% (mean +/- SD, n = 20). The beta for the fractal HRV was 1.08 +/- 0.18 (n = 20). With propranolol, these basic properties of fractal HRV dynamics remained unchanged despite an increase in the mean RR interval (placebo, 912 +/- 111 ms; propranolol, 1,134 +/- 133 ms, P < 0.05) and a change in the harmonic spectral shape evaluated by LF/HF (placebo, 2.76 +/- 1.57; propranolol, 1.82 +/- 0.81, P < 0.05). For short-term data, less power was extracted as fractal because of the absence of the very low frequency component, yet the beta and LF/HF were unchanged from long-term data. These findings indicate that 1) the observed inversely proportional frequency (1/f) spectrum in human resting HRV is due to underlying random fractal dynamics and 2) the sympathetic nervous system seemed to play a minor role in modulating the fractal HRV dynamics.
Tissue-specific increase in norepinephrine turnover by central interleukin-1, but not by interleukin-6, in rats
Authors: Terao A. , Oikawa M. , Saito M.
Published: December 2017

To examine the effects of brain cytokines on the sympathetic nervous system, norepinephrine (NE) turnover in peripheral organs (spleen, lung, diaphragm, pancreas, heart, liver, kidney, and interscapular brown adipose tissue) was assessed after intraperitoneal or intracerbroventricular administrations of human recombinant interleukin (IL)-1 beta and IL-6 in rats. An intraperitoneal injection of IL-1 (1 microgram/rat) accelerated NE turnover in the spleen, lung, diaphragm, and pancreas without appreciable effects in other organs examined. When IL-1 was injected intracerebroventricularly at much lower doses (1-100 ng/rat), a dose-dependent increase in NE turnover was observed in the spleen, lung, diaphragm, and pancreas. IL-6 did not affect NE turnover in every organ examined, even when it was given at much higher doses, 100 micrograms/rat and 100 ng/rat for intraperitoneal and intracerebroventricular injections, respectively. In contrast to tissue NE turnover, plasma corticosterone level was increased after the administration of IL-6 as well as IL-1, regardless of the site of administration. These results suggest that central IL-1, but not IL-6, increases sympathetic nerve activity in some specific organs, whereas both cytokines are effective for adrenocortical activation. A possible role of the sympathetic nervous system in physiological and immune responses to central IL-1 was discussed.
Control of erythropoiesis in humans during prolonged exposure to the altitude of 6,542 m
Authors: Richalet J. P. , Souberbielle J. C. , Antezana A. M. , Dechaux M. , Le Trong J. L. , Bienvenu A. , Daniel F. , Blanchot C. , Zittoun J.
Published: December 2017

Altitude hypoxia induces an increase in erythropoiesis. Some of the factors involved in the control of altitude polycythemia were studied. Ten subjects (4 women, 6 men) were exposed for 3 wk to extreme altitude (6,542 m). Blood was withdrawn in normoxia (N) and after 1 wk (H1), 2 wk (H2), or 3 wk (H3) at 6,542 m for the measurement of serum erythropoietin (EPO), blood hemoglobin (Hb), hematocrit (Hct), intraerythrocyte folate (Fol), and plasma ferritin (Fer) concentrations. Renal blood flow (RBF) and absolute proximal reabsorption rate (APR) were measured by the p-aminohippuric acid and lithium clearance, respectively, in N and H2 conditions. O2 supply to the kidneys was calculated using RBF and arterial O2 content (CaO2). After an initial sharp increase in EPO, it decreased at H2 and H3. Hct and Hb increased from N to H1 and H2 and then unexpectedly decreased from H2 to H3. Mean corpuscular Hb content (MCHC = Hb/Hct) was lower in all H than in N conditions. Increase in EPO at H1 varied from 3- to 134-fold among individuals. Women showed a smaller increase in Hct and Hb and a greater decrease in MCHC. Two women showed a large increase in EPO without increase in Hb. Fol was not modified by altitude hypoxia. Fer showed a marked decrease in H1 and H3 compared with N. Hb was positively related to Fer in hypoxia. Iron intake in food was markedly decreased during the 2-wk ascent to 6,542 m. EPO was inversely related to CaO2 and positively related to APR.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in muscle sympathetic nerve activity and renal function during positive-pressure breathing in humans
Authors: Tanaka S. , Sagawa S. , Miki K. , Claybaugh J. R. , Shiraki K.
Published: December 2017

The possibility that the decreased urinary flow during continuous positive-pressure breathing (CPPB) may be a consequence of a reflex mediated via the cardiopulmonary baroreceptors to increase neurohumoral secretion or to change the sympathetic outflow was assessed. Muscle sympathetic nerve activity (MSNA) on the right peroneal nerve, vasoactive hormones, and renal and cardiovascular responses were measured during CPPB (+12 mmHg) in 10 male subjects (22.0 +/- 0.6 yr, 66.8 +/- 1.5 kg body wt). The experiments consisted of a 1-h control, 1 h with CPPB (experimental) or without CPPB (a time control), and a 1-h recovery period. Two blood samples were taken during each period for measurements of arginine vasopressin (AVP), plasma aldosterone (PAldo), plasma renin activity (PRA), norepinephrine, and atrial natriuretic peptide (ANP), and urine was collected hourly for the measurement of urine volume and electrolytes and clearances. MSNA rapidly increased (P < 0.05) at the onset of CPPB, continued to increase during exposure, and rapidly returned to the normal level at recovery. The MSNA changes coincided with increased plasma NE and were concurrent with a reduced (P < 0.05) urine output associated with a reduction of both free water and osmolal clearances, Na+ and osmolal excretions, and creatinine clearance (glomerular filtration rate). AVP and PRA increased (P < 0.05), whereas PAldo and ANP were unchanged. The results are consistent with the concept that increased sympathetic outflow may play a role in the reduction of urinary output and Na+ excretion during unloading of the cardiopulmonary receptors.
Meal patterns of macronutrient intake in rats with particular dietary preferences
Authors: Shor-Posner G. , Brennan G. , Ian C. , Jasaitis R. , Madhu K. , Leibowitz S. F.
Published: December 2017

In the present study, we examined, via computer-assisted analyses, the nocturnal meal patterns of male albino Sprague-Dawley rats with clear differences in their individual preferences for the macronutrients, protein, carbohydrate, and fat. Rats exhibiting a strong preference for the carbohydrate diet over the 12-h nocturnal cycle (approximately 50% of the group) consumed fewer total calories and relatively small, more frequent meals, compared with rats that preferred protein or fat. Moreover, the first meal of the feeding cycle was identified as being most distinctive in reflecting the individual dietary preferences of these rats. This contrasts with the subsequent meals, which for all rats showed a general trend of increasing proportions of protein and fat and a decreasing concentration of carbohydrate. Only the high-fat rats (approximately 30% of the group) were further distinguished by a particularly large fat-predominant meal in the middle-dark period, which was then followed by smaller fat-rich meals in the late-dark period. These fat-preferring rats exhibited significantly greater body weight gain compared with rats preferring carbohydrate.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of simulated microgravity on cardiopulmonary baroreflex control of forearm vascular resistance
Authors: Convertino V. A. , Doerr D. F. , Ludwig D. A. , Vernikos J.
Published: December 2017

The stimulus-response characteristics of cardiopulmonary baroreflex control of forearm vascular resistance (FVR) were studied in 11 healthy men before and after 7 days of 6 degrees head-down bedrest to test the hypothesis that microgravity alters this reflex response. We assessed the relationship between stimulus [changes in central venous pressure (delta CVP)] and reflex response (delta FVR) during unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP; 0 to -20 mmHg). delta CVP during bedrest and LBNP was estimated from peripheral vein pressures in the dependent right arm. Compared with prebedrest baseline, plasma volume and estimated CVP were decreased by 13 and 33%, respectively, at 7 days of bedrest. Progressive reflex forearm vasoconstriction occurred in response to graded reductions in estimated CVP during LBNP, and delta FVR per unit delta CVP was doubled after bedrest. The increase in sensitivity of the cardiopulmonary baroreflex control of FVR was related to reduced circulating blood volume, suggesting that enhanced peripheral vasoconstriction in individuals adapted to microgravity can be attributed, in part, to hypovolemia. In addition, microgravity appears to alter the stimulus for cardiopulmonary baroreceptors to a lower operational range of CVP, suggesting the possibility of chronic resetting.
The relationship between renin isoelectric forms and renin glycoforms
Authors: Katz S. A. , Opsahl J. A. , Abraham P. A. , Gardner M. J.
Published: December 2017

Active renin can be separated into multiple isoelectric forms using shallow gradient isoelectric focusing and into multiple glycoforms using concanavalin A (Con A) affinity chromatography. The relationship between renin isoelectric forms and glycoforms has not been previously determined. In this study, each of three renin Con A glycoforms from rat kidney was composed of significantly different proportions of six renin isoelectric forms; glycoforms with the greatest affinity for Con A contained proportionally less of the acidic isoelectric forms than those with the least affinity for Con A. A set of compartmental models accurately predicted previously measured differential plasma clearance rates of the three renin glycoforms based on their corresponding isoelectric form proportions. We conclude that 1) each Con A renin glycoform is composed of significantly different proportions of isoelectric forms, and 2) the different proportions of isoelectric forms found in Con A glycoforms are sufficient to account for the differential renin plasma clearance rates demonstrated previously for renin glycoforms in the rat. These data suggest that the isoelectric and glycoform heterogeneity of active renin are, in fact, closely related and may result from variable and interrelated mannose (Con A affinity) and sialic acid (charge) attachments to renin.
Control of red cell function of late chick embryos: role of extracellular ATP/AMP and egg size
Authors: Koller M. , Dragon S. , Baumann R.
Published: December 2017

Hypoxia is the alleged stimulus for initiation of increase of carbonic anhydrase II (CAII) and 2,3-diphosphoglycerate (2,3-DPG) synthesis of red blood cells from late chick embryos. The PO2-dependent regulation of red cell metabolism is mediated by unknown humoral factors [Million et al., Am. J. Physiol. 261 (Regulatory Integrative Comp. Physiol. 30): R1188-R1196, 1991]. In the present investigation we have analyzed whether interindividual differences in egg size (which result in different surface area-to-mass ratios) affect the timing of initiation of 2,3-DPG and CAII synthesis in late chick embryos. We also investigated the effect of extracellular adenine nucleotides on red cell organic phosphate pattern and O2 affinity to test whether the inhibitory effect of normal or elevated PO2 on 2,3-DPG synthesis and the concomitant increase of ATP (and O2 half-saturation pressure) can be mimicked by these agents. The results show that differences in egg size affect the timing of CAII and 2,3-DPG synthesis, indicating that PO2-dependent regulation of red cell function allows adjustment to the properties of the individual egg. We also found that extracellular ATP, which is rapidly degraded to AMP by red cell ectoenzymes, can alter the red cell phosphate pattern and O2 affinity, i.e., significantly increase red cell ATP, decrease red cell 2,3-DPG and O2 affinity, and thus mimic the effect of normoxia and hyperoxia. These findings suggest that extracellular adenine nucleotides may be involved in the PO2-dependent regulation of embryonic red cell metabolism.