bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucocorticoids alter fever and IL-6 responses to psychological stress and to lipopolysaccharide
Authors: Morrow L. E. , McClellan J. L. , Conn C. A. , Kluger M. J.
Published: December 2017

The purpose of this study was to determine whether glucocorticoids exert inhibitory feedback on lipopolysaccharide (LPS)-induced fever, stress-induced fever (exposure to an open field), and plasma concentrations of interleukin-6 (IL-6)-like and tumor necrosis factor-alpha (TNF)-like activity in biotelemetered rats. Injections of LPS (50 micrograms/kg) or exposure to an open field (30 min) led to significantly higher fevers in adrenalectomized (ADX) rats than in sham-ADX rats. To test the hypothesis that higher fevers were specifically the result of an absence of glucocorticoids, the glucocorticoid antagonist RU 38486 (20 mg/kg) was administered orally to rats with intact adrenal glands. The RU 38486-treated rats had higher plasma concentrations of IL-6-like activity and developed significantly higher fevers than did vehicle-treated rats. Rats injected intracerebroventricularly with 10 ng RU 38486 also developed higher fevers. Other ADX animals were implanted subcutaneously with replacement corticosterone pellets before exposure to an open field or injection with LPS. In response to an open field or injection with LPS, ADX animals implanted with replacement pellets that mimic plasma concentrations of corticosterone observed in stressed animals (100-mg pellets) developed fevers that were significantly lower than those observed in ADX rats given placebo pellets, but that were not different from fevers in sham-ADX rats given placebo pellets. ADX animals implanted with replacement pellets that mimic plasma concentrations of corticosterone observed in unstressed animals (25-mg pellets) developed fevers that were significantly higher than those observed in sham-ADX rats given placebo pellets, but that were not different from fevers in ADX rats given placebo pellets.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of drinking on thirst and vasopressin in dehydrated elderly men
Authors: Phillips P. A. , Bretherton M. , Risvanis J. , Casley D. , Johnston C. , Gray L.
Published: December 2017

Inhibition of dehydration-induced arginine vasopressin (AVP) secretion and thirst depends on removal of osmotic and hemodynamic stimuli as well as on preabsorptive oropharyngeal factors that reduce thirst and AVP secretion on drinking before correction of the water deficits. Plasma atrial natriuretic peptide (ANP) levels may also change with drinking. Therefore, the thirst and plasma responses to oral water loads (10 ml/kg) in 10 healthy old (64-76 yr) and young (20-32 yr) 24-h water-deprived men were investigated. After 24-h water deprivation plasma sodium, osmolality, and AVP were increased similarly in both groups (P < 0.001). Plasma ANP levels fell after dehydration similarly in both groups (P < 0.05) but were always higher in the older group (P < 0.05). However, although thirst increased in both groups (P < 0.05), this was significantly less in the elderly (P < 0.05). After the water load, thirst was reduced in both groups throughout the study (P < 0.05). However, plasma AVP fell immediately after drinking only in the young group and rose to postdeprivation levels after 15 min. Plasma AVP was not different from postdeprivation throughout in the old group and after 15 min in the young group presumably because the water load was insufficient to replace their water deficits. In the young group only, plasma ANP rose to 182 +/- 43% of postdeprivation levels at 3 min after drinking (P < 0.05). These results demonstrate reduced oropharyngeal inhibition of AVP secretion after drinking in healthy elderly men but maintained inhibition of thirst.
Meal composition affects postprandial fatty acid oxidation
Authors: Surina D. M. , Langhans W. , Pauli R. , Wenk C.
Published: December 2017

The influence of macronutrient content of a meal on postprandial fatty acid oxidation was investigated in 13 Caucasian males after consumption of a high-fat (HF) breakfast (33% carbohydrate, 52% fat, 15% protein) and after an equicaloric high-carbohydrate (HC) breakfast (78% carbohydrate, 6% fat, 15% protein). The HF breakfast contained short- and medium-chain fatty acids, as well as long-chain fatty acids. Respiratory quotient (RQ) and plasma beta-hydroxybutyrate (BHB) were measured during the 3 h after the meal as indicators of whole body substrate oxidation and hepatic fatty acid oxidation, respectively. Plasma levels of free fatty acids (FFA), triglycerides, glucose, insulin, and lactate were also determined because of their relationship to nutrient utilization. RQ was significantly lower and plasma BHB was higher after the HF breakfast than after the HC breakfast, implying that more fat is burned in general and specifically in the liver after an HF meal. As expected, plasma FFA and triglycerides were higher after the HF meal, and insulin and lactate were higher after the HC meal. In sum, oxidation of ingested fat occurred in response to a single HF meal.
Tamoxifen mimics the effects of estradiol on food intake, body weight, and body composition in rats
Authors: Wade G. N. , Heller H. W.
Published: December 2017

Treatment of ovariectomized rats with the nonsteroidal antiestrogen tamoxifen mimicked the effects of estradiol and caused significant decreases in food intake and body weight. The decreases in body weight were reflected mainly in a decreased body fat content, although tamoxifen treatment did suppress linear growth too. Similar to the effects of estradiol, tamoxifen decreased parametrial white adipose tissue wet weight and lipoprotein lipase activity. When given concurrently with estradiol, tamoxifen showed no evidence of antiestrogenic activity on any of these measures. As reported previously, tamoxifen acted as a partial agonist/antagonist for uterine weight. The effective dose of tamoxifen for suppression of food intake, body weight, and body fat content fell between 10 and 50 micrograms/day. Therefore, tamoxifen behaves like other nonsteroidal antiestrogens and mimics but fails to antagonize the actions of estradiol on many aspects of physiological and behavioral regulation of energy balance.
Regulation of pelvic patch water flow in Bufo marinus: role of bladder volume and ANG II
Authors: Parsons R. H. , McDevitt V. , Aggerwal V. , Le Blang T. , Manley K. , Kim N. , Lopez J. , Kenedy A. A.
Published: December 2017

This report examines the importance of bladder volume in regulating cutaneous water uptake (Jv, cm3.cm-2.s-1 x 10(-7)) across the ventral pelvic patch and examines the role of angiotensin II (ANG II) and circulation as the regulatory mechanism. Jv in empty-bladder Bufo marinus (bladder volume 3.89 +/- 1.49%, n = 7) was 1,671 +/- 68 (n = 7). Injection of Ringer solution into the bladder (12.8 +/- 2.2%, n = 7) decreased Jv to 1,025 +/- 202 (n = 7). ANG II injected into toads with filled bladders increased Jv in a dose-dependent manner. At 5 micrograms/100 g toad Jv increased by 136 +/- 63 (n = 6), at 50 micrograms/100 g toad by 432 +/- 82 (n = 7), and at 200 micrograms/100 g toad by 620 +/- 142 (n = 5). Saralasin (200 micrograms/100 g toad) completely inhibited the response to ANG II (50 micrograms/100 g toad) and at 1 mg/100 g toad decreased Jv in empty-bladder toads. These experiments indicate that 1) bladder volume participates in the regulation of Jv in the ventral pelvic patch; 2) ANG II increases the Jv in toads with full bladders; 3) saralasin inhibits the high Jv in empty bladder toads; 4) the high Jv, associated with an empty bladder, requires an intact circulation to be maintained; 5) without an intact circulation, the high water flow associated with an empty bladder causes the Na+ content of the tissue in the ventral patch to be reduced; and 6) ANG II causes only a minimal increases in water permeability in the isolated pelvic patch skin.
Supramedullary inputs to cardiovascular neurons of rostral ventrolateral medulla in rats
Authors: Agarwal S. K. , Calaresu F. R.
Published: December 2017

Experiments were done to test the hypothesis that selective activation of cell bodies in different nuclei known to be involved in central cardiovascular control could excite or inhibit the discharge of neurons in the rostral ventrolateral medulla (RVLM). It is known that chemical stimulation of the lateral parabrachial nucleus (LPBN), locus ceruleus (LC), and lateral hypothalamic area (LHA) in anesthetized animals elicits increases (LPBN) or decreases (LC and LHA) in arterial pressure. We therefore recorded extracellularly spontaneous activity from RVLM units in urethan-anesthetized rats and monitored the changes in firing frequency of these neurons during chemical stimulation of one of LPBN, LC, and LHA. Thirty-two units were classified as cardiovascular neurons because their activity was inhibited by baroreceptor activation (1-3 micrograms phenylephrine iv) and displayed a cardiac cycle-related rhythmicity. Chemical stimulation with sodium glutamate of arterial pressor sites in the ipsilateral LPBN increased the firing frequency (40.3 +/- 1.3%) of 11 cardiovascular neurons. Activation of cell bodies in arterial depressor sites in the ipsilateral LC inhibited the firing rate (59.1 +/- 7.1%) of 10 cardiovascular neurons and excited 1 unit. Activation of cell bodies in arterial depressor sites in the ipsilateral LHA inhibited the discharge rate (25.4 +/- 4.7%) of six cardiovascular neurons, excited one unit, and did not alter the rate of the remaining three units. These results provide direct evidence for the existence of excitatory and inhibitory pathways from neurons located in the LPBN, LC, and LHA to cardiovascular neurons in the RVLM.
Responses to catecholamines in perfused livers of hypothalamic-lesioned rats
Authors: Matsui Y. , Ishibashi H. , Kimura K. , Shiota M. , Ohta M. , Sugano T.
Published: December 2017

The responses of hepatic glycogenolysis to catecholamines in ventromedial hypothalamus (VMH)-lesioned male rats were examined in perfused livers. Seven days after bilateral electrical lesioning of the VMH, the livers were perfused. Isoproterenol, a beta-agonist, stimulated greater glucose production in VMH-lesioned rats than in controls (32.8 vs. 5.6 mumol glucose.h-1.g liver-1), while responses to phenylephrine, an alpha-agonist, decreased significantly compared with controls (44.4 vs. 69.8 mumol glucose.h-1.g liver-1). There were no significant differences in responses of livers to glucagon and vasopressin between control and VMH-lesioned rats. Adrenodemedullation showed the same effect on beta-responses as lesions in the VMH, but no effect on alpha-responses. Plasma epinephrine levels were not detectable with the high-performance liquid chromatography analysis in VMH-lesioned rats. The periodicity of plasma corticosterone levels was observed in both VMH-lesioned and control rats, although daytime increases in plasma corticosterone were blocked by VMH lesions. These results suggest that the lesions in the VMH cause changes in the levels of adrenergic receptor and that the increase in beta-responses is caused mostly by the reduction of plasma epinephrine.
Fate of circulating amino-terminal propeptide of type III procollagen in conscious pigs
Authors: Jensen L. T. , Henriksen J. H. , Risteli J. , Olesen H. P. , Nielsen M. D. , Lorenzen I.
Published: December 2017

The amino-terminal propeptide of type III procollagen (PIIINP, M(r) 42,000) is a promising marker for the formation of type III collagen of granulation tissue in experimental and clinical studies. The disposal kinetics of circulating PIIINP is, however, almost unknown. In conscious pigs with a thoracic duct-venous shunt, 125I-labeled PIIINP was injected intravenously. The initial distribution volume was 2.2 liters, which was 1.7 times the plasma volume (P < 0.01). The disappearance curve was three-phased, with an initial steep decline (t1/2 58 min), followed by two slower phases (t1/2 239 min and 289 h). Consecutive gel filtrations showed that the initial slope of the plasma disappearance curve corresponded to the plasma clearance of the intact PIIINP. The initial plasma clearance was 26.5 ml plasma/min, whereas the urinary clearance was 8.7 ml plasma/min (P < 0.01). The other components of the plasma disappearance curve originated from the formation and disappearance of a high and a low molecular weight (MW) fraction as part of the degradation of PIIINP. The high MW fraction (approximately M(r) 90,000) was similar to a previously described, but not further characterized, PIIINP immunoreactive component. The existence of the low MW fraction (approximately M(r) 20,000) has not been reported before. The lymphatic recirculation of intact PIIINP was rapid, and the lymph-serum ratio was almost constant within 1 h of injection. We conclude that the t1/2 of circulating PIIINP is 58 min, that PIIINP escapes the circulation very quickly, and that the degradation of PIIINP includes at least two intermediary steps.
Reanalysis of the rat proestrous LH surge by deconvolution analysis
Authors: Veldhuis J. D. , Johnson M. L. , Gallo R. V.
Published: December 2017

To evaluate the temporal mechanisms that give rise to the spontaneous proestrous surge of luteinizing hormone (LH) in the rat, we have applied deconvolution analysis to earlier immunoreactive LH concentration vs. time profiles obtained by sampling blood in proestrus at 2- to 3-min intervals in 10 animals over a span of 160-300 min. Six other animals were bled in 6-min intervals on day 1 of diestrus. Deconvolution analysis permitted us to calculate the number, duration, amplitude (maximal release rates), and mass of underlying LH secretory bursts and to simultaneously estimate basal secretion and the half-life of endogenous LH in each animal. Proestrus rats exhibited a significant increase in the number of computer-identified LH secretory bursts per hour (1.8 +/- 0.2 vs. 1.1 +/- 0.01 on diestrus, P < 0.01), with a corresponding reduction in the LH intersecretory burst interval from 61 +/- 6.4 min (diestrus) to 25 +/- 2.7 min (proestrus, P < 0.01). There was a remarkable 16-fold increase in the mass of LH secreted per burst, which rose from 72 +/- 5.2 to 1,230 +/- 200 ng/ml (P < 0.01). This resulted from a sixfold increase in LH secretory burst amplitude and a doubling of burst duration. The total amount of LH released in a burstlike fashion during the proestrous LH surge rose 20-fold, and calculated basal LH secretion increased to approximately 25% of this value. Of interest, the computed half-life of endogenous LH also increased from 10 +/- 1.1 to 19 +/- 3.7 min (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Raphe pallidus excites a unique class of sympathetic preganglionic neurons
Authors: Morrison S. F.
Published: December 2017

The responses of splanchnic sympathetic preganglionic neurons (SPNs) to stimulation in raphe pallidus and in rostral ventrolateral medulla (RVLM) were compared to determine the basis for the excitatory responses evoked in the whole splanchnic preganglionic nerve bundle. Most (88%) of the SPNs with a short-latency (32 ms) excitatory response to RVLM stimulation were unaffected by raphe pallidus stimulation, although 12% were excited at a long latency (123 ms). Each of the SPNs with long-latency (114 ms) excitatory responses to RVLM stimulation was also excited by raphe pallidus stimulation at latencies (106 ms) that were 7 ms (P < 0.01) shorter than those evoked from the RVLM. Antidromic activation of raphe pallidus neurons from both the T8 intermediolateral nucleus (98 ms) and from the RVLM (18 ms) indicated that their spinally projecting axons emit collaterals (mean conduction time: 12 ms) into the ventrolateral medulla. In conclusion, the short-latency (70 ms) splanchnic nerve excitation evoked by RVLM stimulation is mediated primarily by SPNs that do not respond to raphe pallidus stimulation. Similarly, the long-latency (162 ms) splanchnic excitation evoked from the raphe pallidus is mediated primarily by SPNs that do not respond to the rapidly conducting sympathoexcitatory pathway from the RVLM. The long-latency (169 ms), RVLM stimulus-evoked excitation of the splanchnic nerve may arise from action potentials conducted on the axonal branches of raphe spinal neurons.
Enhanced response of muscle protein synthesis and plasma insulin to food intake in suckled rats
Authors: Davis T. A. , Fiorotto M. L. , Nguyen H. V. , Reeds P. J.
Published: December 2017

To compare the sensitivity of muscle protein synthesis to food intake in neonatal and weaned rats, 5- and 16-day-old suckled rats and 28-day-old weaned rats were either fed, fasted for 8-10 h, or refed for 1-4 h after an 8-h fast. Protein synthesis was measured in vivo in soleus and plantaris muscles with a large dose of L-[4-3H]phenylalanine. In fed rats, fractional rates of protein synthesis (KS) decreased with age. Fasting decreased KS, and refeeding increased KS most in 5-day-old animals, less in 16-day-old rats, and least in 28-day-old rats. In 5-day-old rats, there were no differences in KS between soleus and plantaris muscles in the fed state and after fasting and refeeding; at 28 days, KS was higher in soleus than in plantaris in fed rats, and the soleus did not respond to fasting and refeeding. In rats at all three ages, the concentration of most plasma amino acids decreased during fasting; when 5-day-old rats were refed, plasma amino acid concentrations increased, but not to the levels in the fed state. Plasma insulin concentrations increased with age. Plasma insulin concentrations decreased more rapidly with fasting and increased more extensively with refeeding in 5-day-old rats than in older rats. These results suggest that muscle protein synthesis is more responsive to food intake in young suckled rats than in older suckled or weaned rats; this increased responsiveness is accompanied by greater changes in circulating insulin concentrations.
Biphasic intracellular redistribution of alpha 1-adrenergic receptors in rat liver during sepsis
Authors: Hwang T. L. , Lau Y. T. , Chen M. F. , Tang C. , Liu M. S.
Published: December 2017

Changes in the distribution of alpha 1-adrenergic receptors in two subcellular fractions, the plasma membrane and the light vesicle, of rat liver during sepsis were studied using [3H]prazosin binding and photoaffinity labeling with [125I]arylazidoprazosin in combination with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Sepsis was induced by cecal ligation and puncture (CLP). Septic rats exhibit two metabolically distinct phases: an initial hypermetabolic (hyperglycemic) phase (9 h after CLP; early sepsis) followed by a hypometabolic (hypoglycemic) phase (18 h after CLP; late sepsis). [3H]prazosin binding studies show that during early sepsis, the maximal binding capacity (Bmax) was increased by 35% in plasma membranes but was decreased by 28% in light vesicles; while during late sepsis, the Bmax was decreased by 30% in plasma membranes but was increased by 33% in light vesicles. The photoaffinity labeling studies revealed two major binding peptides with M(r) of 77,000 and 68,000 Da and one minor binding protein with M(r) of 39,000 Da. The total binding for the three labeled peptides during early sepsis was increased by 26% in plasma membranes but was decreased by 33% in light vesicles, while during late sepsis the total binding was decreased by 19% in plasma membranes but was increased by 35% in light vesicles. These data indicate that alpha 1-adrenergic receptors in the rat liver were externalized from light vesicles to plasma membranes during the hyperglycemic phase while they were internalized from surface membranes to intracellular sites during the hypoglycemic phase of sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
Neuropeptide Y inhibits chloride secretion in the shark rectal gland
Authors: Silva P. , Epstein F. H. , Karnaky K. J. , Reichlin S. , Forrest J. N.
Published: December 2017

We studied the effects of the 36-amino acid peptide, neuropeptide Y (NPY), on salt secretion by the rectal gland of Squalus acanthias. We used three preparations: whole isolated perfused glands, freshly prepared separated rectal gland tubules, and confluent monolayers of cultured rectal gland cells. In perfused glands NPY inhibited secretion stimulated by vasoactive intestinal peptide (VIP), forskolin, or adenosine 3',5'-cyclic monophosphate (cAMP) and theophylline. Maximal inhibition of 63 +/- 3.4% was seen at 3 x 10(-8) M NPY, with half-maximal effect at 3 x 10(-9) M. NPY did not inhibit the basal activity of rectal gland adenylate cyclase or that stimulated by VIP. The inhibitory action of NPY was not prevented by procaine, nifedipine, or diltiazem, suggesting that it was not secondary to the release of somatostatin or other unknown neurotransmitters from rectal gland nerves. In confirmation, somatostatin was not detected in the venous effluent after administration of NPY. NPY also inhibited transport-related oxygen consumption in separated rectal gland tubules and inhibited short-circuit current generated by confluent monolayers of primary cultures of rectal gland cells. The results indicate that NPY inhibits chloride secretion by a direct action on cells of the shark rectal gland at a site distal to the generation of cAMP.
Ventilatory CO2-induced optical activity changes of cat ventral medullary surface
Authors: Dong X. W. , Gozal D. , Rector D. M. , Harper R. M.
Published: December 2017

We examined neuronal activation of the ventral medullary surface (VMS) during hypercapnic challenges using optical recording procedures. With a coherent imaging probe, we assessed reflected 700-nm light from 18 VMS sites in 11 spontaneously breathing adult cats and from the suprasylvian cortex in two cats. Video frames were acquired during a baseline period, hypercapnic (3, 5, and 10% CO2 in O2) exposure, and recovery. Hypercapnic exposure elicited overall reflectance changes in all VMS sites, but no changes in the suprasylvian cortex. Light reflectance changes, suggesting altered neuronal activity, were reproducible, occurred as early as 30 s after CO2 exposure, and were dose dependent. The changes persisted approximately 20-25 min beyond the stimulus, but respiratory responses consistently recovered within 2-3 min. Although more rostral VMS sites tended to be associated with decreased activity and caudal regions with increased excitation, no uniform topographical organization was apparent across animals. The variability in VMS optical reflectance patterns across animals during CO2 stimulation may reflect the heterogeneous topographical distribution of responsive neurons in the structure.
A comparison of inhibitory effects of neuropeptide Y on rat urinary bladder, urethra, and vas deferens
Authors: Zoubek J. , Somogyi G. T. , De Groat W. C.
Published: December 2017

The effects of human and porcine neuropeptide Y (NPY) on electrically induced contractions of smooth muscle strips from rat urinary bladder, urethra, and vas deferens were investigated. NPY (10 nM-10 microM) inhibited to the contractile response in all preparations. The magnitude of inhibition by NPY was dependent on frequency of stimulation in each organ, the inhibition being in general much greater (80-100%) at low frequencies (2-5 Hz) than at high frequencies (30-40% at 10-100 Hz). The vas deferens and urethra exhibited nearly maximal inhibition (90-100%) over a broader range of stimulus frequencies (1-20 Hz), while the bladder exhibited a more prominent inhibition at frequencies of stimulation below 2 Hz. When tested at 20 Hz stimulation the urethra and vas deferens were very sensitive (70-90% inhibition) to both types of NPY, whereas bladder strips were much less sensitive to NPY and the effect differed with the two types of NPY (16% inhibition with human NPY and 39% inhibition with porcine NPY). In the urinary bladder, NPY inhibited the cholinergic component of the contractile response, while in the urethra adrenergic transmission was primarily affected. These studies suggest that NPY, which is present in both cholinergic and adrenergic neurons in the pelvic ganglia, may have an important role in the neural control of the lower urinary tract by participating in autoinhibition at autonomic nerve terminals as well as in the heterosynaptic interactions between the cholinergic and adrenergic pathways.
Norepinephrine- and insulin-resistant glucose transport in brown adipocytes from diabetic SHR/N-cp rats
Authors: Marette A. , Mauriege P. , Despres J. P. , Tulp O. L. , Bukowiecki L. J.
Published: December 2017

The effects of norepinephrine and insulin on glucose transport were investigated in brown adipocytes isolated from obese nondiabetic Lister and Albany (LA/N-cp strain) rats (O-LA), obese diabetic spontaneously hypertensive (SHR/N-cp strain) rats (O-SHR), and from their lean (L) controls to test whether the decreased calorigenic response to norepinephrine of O-SHR adipocytes was specifically associated with alterations in glucose metabolism. Norepinephrine and insulin independently stimulated glucose transport in L-LA, O-LA, and L-SHR brown adipocytes, but their stimulatory effects were markedly reduced in O-SHR cells. Both insulin responsiveness and the total number of insulin receptors were significantly decreased in O-SHR adipocytes but not in O-LA cells. The number of high-affinity beta 1/beta 2-adrenoceptors was significantly increased (+70%) in O-LA adipocytes but was similar in L-SHR and O-SHR cells. These results indicate that 1) major metabolic defects are present in brown adipose tissue (BAT) of O-SHR but not of O-LA, although these two strains are homozygous for the cp allele, 2) postreceptor defects are predominantly involved in O-SHR adipocyte refractoriness to norepinephrine, and 3) a reduced mitochondrial content may represent the principal metabolic alteration explaining the decreased effects of norepinephrine on both thermogenesis and glucose transport. It is postulated that the marked insulin resistance of O-SHR leads to a decreased mitochondriogenesis in BAT, resulting in a diminished tissue thermogenic capacity and reduced glucose metabolism, thereby contributing to obesity and diabetes.
Abdominal vagotomy dissociates the anorectic mechanisms for peripheral serotonin and cholecystokinin
Authors: Eberle-Wang K. , Levitt P. , Simansky K. J.
Published: December 2017

These studies compared the effects of total abdominal vagotomy (VGX) on ingestive actions produced by peripheral serotonergic and cholecystokinergic (CCKergic) stimulation in rats. Subcutaneous injection of 0.01-0.16 mumol/kg of the serotonin (5-HT) analogue 5-carboxamidotryptamine (5-CT) dose-dependently reduced mash intake equally in VGX rats and their laparotomized (LAP) controls but concurrently stimulated drinking only in the controls. The sulfated octapeptide of cholecystokinin (CCK-8, 4.0 nmol/kg ip) also reduced food intake only in the controls. In a second set of rats, vagotomy did not alter anorexia after intraperitoneal administration of either 2.0 or 8.0 mumol/kg of 5-HT or of 0.03 mumol/kg of 5-CT but abolished anorexia after a large dose of CCK-8 (8.0 nmol/kg). The completeness of vagotomy was verified histologically by immunohistochemical staining of the vagal bundles for the high molecular weight form of neurofilament-H protein. We report for the first time that 5-CT produces anorexia by a vagally independent mechanism. In contrast, 5-CT stimulates drinking by a pathway that does involve vagal function. Finally, we confirm the prediction that vagotomy dissociates the neural mechanisms for the anorectic action of peripheral 5-HTergic and CCKergic stimulation.
The heart works against gravity
Authors: Seymour R. S. , Hargens A. R. , Pedley T. J.
Published: December 2017

The circulatory systems of vertebrate animals are closed, and blood leaves and returns to the heart at the same level. It is often concluded, therefore, that the heart works only against the viscous resistance of the system, not against gravity, even in vascular loops above the heart in which the siphon principle operates. However, we argue that the siphon principle does not assist blood flow in superior vascular loops if any of the descending vasculature is collapsible. If central arterial blood pressure is insufficient to support a blood column between the heart and the head, blood flow ceases because of vascular collapse. Furthermore, the siphon principle does not assist the heart even when a continuous stream of blood is flowing in a superior loop. The potential energy gained by blood as it is pumped to the head is lost to friction in partially collapsed descending vessels and thus is not regained. Application of the Poiseuille equation to flow in collapsible vessels is limited; resistance depends on flow rate in partially collapsed vessels with no transmural pressure difference, but flow rate is independent of resistance. Thus the pressure developed by the heart to establish a given flow rate is independent of the resistance occurring in the partially collapsed vessels. The pressure depends only on the height of the blood column and the resistance in the noncollapsed parts of the system. Simple laboratory models, involving water flow in collapsible tubing, dispel the idea that the siphon principle facilitates blood flow and suggest that previously published results may have been affected by experimental artifact.
The effect of pregnancy on the response to the TxA2/PGH2 analogue U-46619 in rabbits
Authors: Losonczy G. , Mucha I. , DiPirro J. , Sweeney J. , Brown G. , Brentjens J. , Venuto R.
Published: December 2017

We compared the hemodynamic actions of U-46619, a stable thromboxane A2 (TxA2) prostaglandin H2 (PGH2) analogue, in nonpregnant (NP) rabbits with those observed in late pregnant (P) rabbits. An intravenous injection of U-46619 (10 micrograms) to each of eight NP chronically instrumented rabbits (mean body weight 3.4 kg) induced an immediate (1 min) and reversible fall of cardiac output (CO, 66%) and mean arterial pressure (MAP, 41%, both P < 0.01). P rabbits (n = 6, mean body weight 3.8 kg), however, responded with an elevation of MAP (5%, P < 0.02) upon intravenous injection of the drug (10 micrograms), while CO remained unchanged. The fall of CO in NP rabbits was associated with the temporary disappearance of a fraction of circulating platelets between the superior vena cava and the aortic arch. The number of platelets at 30 and 60 s after U-46619 was reduced (P < 0.05) by 14 and 20% respectively in the aortic blood, whereas caval platelet counts were unchanged until 90 s (-6%, P < 0.05). In contrast, intraaortic administration of this drug (10 micrograms) to NP rabbits resulted in neither thrombocytopenia nor hypotension. U-46619 (10-30 micrograms i.v.) caused no decrease in platelet count in the aorta of P rabbits. In vitro, U-46619-induced aggregation of platelets harvested from P rabbits was also blunted (P < 0.001). This could not be attributed to reduced affinity or number of platelet thromboxane receptors. The data indicate that U-46619 induces a fall of arterial pressure simultaneous with intravascular platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)
Coronary vasoconstrictor pathway from anterior hypothalamus includes neurons in RVLM
Authors: Goodson A. R. , LaMaster T. S. , Gutterman D. D.
Published: December 2017

We have previously identified discrete brain sites [anterior (AHA) and lateral hypothalamus, periaqueductal gray, pontine parabrachial nucleus, lateral reticular formation, and rostral ventrolateral medulla (RVLM)] in the cat, in which electrical or chemical activation produces coronary vasoconstriction. This study examines whether the most rostral (AHA) and caudal (RVLM) of these sites are connected as part of a common pathway mediating coronary vasoconstriction. In chloralose-anesthetized cats, electrical stimulation in the AHA produced maximum increases in arterial pressure (41 +/- 10%) and coronary vascular resistance (28 +/- 9%). Microinjection of lidocaine into the RVLM attenuated the increases in arterial pressure (10 +/- 3%) and coronary vascular resistance (5 +/- 1%) in response to electrical stimulation in the AHA (P < 0.05 vs. before lidocaine). Lidocaine nonspecifically inhibits neural elements in the region. gamma-Aminobutyric acid in the RVLM, which selectively inhibits cell bodies and not fibers passing through the RVLM, attenuated the increase in coronary vascular resistance (38 +/- 8 to 14 +/- 3%; P < 0.05) but not the increase in arterial pressure (87 +/- 12 to 92 +/- 16%) in response to electrical stimulation in the AHA. These data indicate that coronary vasoconstriction in response to electrical stimulation in the AHA requires cell bodies in the RVLM; however, the associated pressor response is mediated by fibers passing through the RVLM. We conclude that a polysynaptic descending pathway that mediates sympathetic coronary vasoconstriction descends from the AHA through a synaptic connection in the RVLM.
What does changing the temperature do to the melatonin rhythm in cultured chick pineal cells?
Authors: Zatz M. , Lange G. D. , Rollag M. D.
Published: December 2017

Chick pineal cells in static culture display a persistent, photosensitive circadian rhythm of melatonin production and release. We previously described the effects of light, the major physiological regulator of circadian rhythms, on the amplitude, period, and phase of the melatonin rhythm. Here we describe the effects of temperature, another physiological regulator of circadian rhythms, on the amplitude, period, and phase of this rhythm. Maintaining cells at 40.0-43.3 degrees C (104-110 degrees F) instead of 36.7 degrees C (98 degrees F) doubled the amplitude of the melatonin rhythm. In contrast, amplitude was reduced by about half at 33.3 degrees C (92 degrees F), and at 46.7 degrees C (116 degrees F) melatonin production was stopped within a few hours. Although temperatures of 40.0-43.3 degrees C raised melatonin output (unlike light, which suppresses it), they lengthened the period of the rhythm (as does constant light). Exposure of cells to 8-h pulses of these temperatures (40.0-43.3 degrees C) induced both phase delays and phase advances of the rhythm in subsequent cycles, with a phase dependence similar to that for the phase shifts induced by light pulses. Pulses of 40.0-43.3 degrees C were, however, weaker in their phase-shifting effects than light pulses. Pulses at still higher temperatures (46.7 degrees C) markedly inhibited melatonin output and delayed or disrupted the rhythm. The relationships (physiological and mechanistic) between the effects of temperature and light on the melatonin rhythm remain to be determined.
Band 3 modulation and hypotonic-stimulated taurine efflux in skate erythrocytes
Authors: Musch M. W. , Leffingwell T. R. , Goldstein L.
Published: December 2017

Previous studies have shown that exposure of skate erythrocytes to hypotonic medium or isosmotic medium with permeant solutes such as ethylene glycol or ammonium chloride increases cell volume. Initial swelling is followed by a regulatory volume decrease accomplished by efflux of cell solutes, including the beta-amino acid taurine. Taurine efflux, as well as the cell volume recovery, is inhibited by stilbene disulfonates and other anion exchange inhibitors, suggesting involvement of the erythrocyte anion exchanger band 3. In the present study we show that binding of the stilbene dihydro 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (H2DIDS) to intact cells doubles after exposure to one-half hypotonic medium. Binding also increases after exposure of erythrocytes to medium of one-third hypotonic medium and ethylene glycol medium, but DIDS binding is not significantly elevated in ammonium chloride medium. To investigate possible mechanisms for modulation of band 3, cells were labeled with 32PO4 and levels of protein phosphorylation determined. Phosphorylation of three proteins of molecular masses of 99, 65, and 32 kDa increases with hypotonic stress. Because the anion exchanger migrates with molecular mass near 100 kDa, the anion exchanger was immunoprecipitated. Hypotonic stress induces a rapid and persistent increase in the 32PO4 phosphorylation of the exchanger. This modification may be responsible for the increased DIDS binding and could be related to stimulated taurine efflux.
Long-term mineralocorticoid-induced changes in rat neuron properties plus interaction of aldosterone and ANG II
Authors: Thornton S. N. , Nicolaidis S.
Published: December 2017

The central site of action and the neuronal mechanism of the robust sodium appetite initiated in rats by the synergistic action of a peripheral priming with mineralocorticoid [deoxycorticosterone acetate (DOCA)] and subsequent central angiotensin II (ANG II) were investigated using iontophoretic and electrophysiological techniques in urethan-anesthetized, DOCA-pretreated (0.5 mg/day sc for 3 days) or nonpretreated male Wistar rats. A significantly greater number of spontaneously active neurons were recorded in the medial septum and median preoptic area, but not in the cortex, in rats pretreated with DOCA than found in the nonpretreated animals (9.3 +/- 1.2 per electrode descent; n = 19 vs. 6.1 +/- 0.7 per descent; n = 21; P < 0.001). The firing rate of the spontaneously active neurons was also significantly increased in the DOCA-pretreated animals. A greatly increased neuronal sensitivity (increased activity lasting up to 10 min after the end of the application) to iontophoretically applied ANG II was found in 32% of the ANG II-sensitive neurons in pretreated animals. This prolonged response was never observed in the nonpretreated animals. Iontophoretically applied aldosterone produces rapid neuronal excitation in both groups of rats and renders previously insensitive neurons sensitive to iontophoretically applied ANG II only in the DOCA-pretreated animals. This forebrain region, therefore, contains neurons that undergo a mineralocorticoid pretreatment-induced and/or a rapid aldosterone-induced sensitization to ANG II, which may be the neuronal mechanism whereby a persistent sodium appetite, induced by the synergistic action of these two hormones, is stimulated.
Blood volume response to drainage of left thoracic duct lymph in the ovine fetus
Authors: Brace R. A.
Published: December 2017

Although it is known that left thoracic duct lymph flow rate in the ovine fetus is several times that in the adult relative to body weight, the role of the lymphatic system in maintaining fetal blood volume has not been explored. In the present study, the left thoracic lymph duct was drained without return to the fetal circulation in 10 chronically catheterized animals for 7 h. Four experiments in which the lymph was returned to the circulation served as control. During the 7-h drainage, the total volume drained was 174.4 +/- 19.6 ml. Thoracic duct lymph flow rate decreased gradually and averaged 22.2 +/- 3.4% (SE) below control at 6-7 h compared with a small increase in the control experiments (analysis of variance: P = 0.0013 comparing 2 groups). Fetal blood volume decreased (P < 0.0001) by 8.2 +/- 1.1% at 3 h because of a decrease in plasma volume with a further small decrease in blood volume to 9.7 +/- 0.9% below normal at 7 h. The decreases in blood volume at 1, 3, 5, and 7 h were 49.5, 40.2, 24.6, and 21.7%, respectively, of the volume of lymph that was drained. Fetal vascular pressures and heart rate did not change significantly. Although protein concentrations in plasma (-6.8 +/- 1.3%) and lymph (-7.5 +/- 2.1%) decreased, the lymph-to-plasma protein concentration ratio remained constant at 0.72 +/- 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of adrenergic and cholinergic blockade on insulin-induced stimulation of calf blood flow in humans
Authors: Randin D. , Vollenweider P. , Tappy L. , Jequier E. , Nicod P. , Scherrer U.
Published: December 2017

Euglycemic hyperinsulinemia stimulates both sympathetic nerve activity and blood flow to skeletal muscle, but the mechanism is unknown. Possible mechanisms that may stimulate muscle blood flow include neural, humoral, or metabolic effects of insulin. To determine whether such insulin-induced vasodilation is modulated by stimulation of adrenergic or cholinergic mechanisms, we obtained, in eight healthy lean subjects, plethysmographic measurements of calf blood flow during 3 h of hyperinsulinemic (1 mU.kg-1.min-1) euglycemic clamp performed alone or during concomitant beta-adrenergic (propranolol infusion), cholinergic (atropine infusion), or alpha-adrenergic (prazosin administration) blockade. Euglycemic hyperinsulinemia alone increased calf blood flow by 38 +/- 10% (means +/- SE) and decreased vascular resistance by 27 +/- 4% (P < 0.01). The principal new observation is that these insulin-induced vasodilatory responses were not attenuated by concomitant propranolol or atropine infusion, nor were they potentiated by prazosin administration. In conclusion, these findings provide evidence that during euglycemic hyperinsulinemia in lean healthy humans stimulation of muscle blood flow is not mediated primarily by beta-adrenergic or cholinergic mechanisms. Furthermore, alpha-adrenergic mechanisms do not markedly limit insulin-induced stimulation of muscle blood flow.
The VMH-dietary obese rat: a new model of non-insulin-dependent diabetes mellitus
Authors: Axen K. V. , Li X. , Fung K. , Sclafani A.
Published: December 2017

A model of non-insulin-dependent diabetes mellitus (NIDDM) has been developed in adult rats by combining bilateral electrolytic lesions of the ventromedial hypothalamus (VMH) and high fat-high sucrose diets. VMH-dietary obese rats showed fasting hyperinsulinemia (> or = 540 pM) and hypertriglyceridemia (> or = 180 mg/dl) generally within 3 wk on the protocol. Fasting hyperglycemia (> or = 10 mM) was observed in the majority of animals in seven consecutive experiments. Hyperglycemic animals showed impaired glucose tolerance despite high prevailing insulin levels. Pancreatic islets isolated from VMH-dietary obese rats showed a loss of insulin secretory response to glucose by week 5, before the onset of hyperglycemia. Islets from hyperglycemic rats no longer responded to an increase in glucose concentration and failed to suppress insulin release normally in response to 15 nM norepinephrine or to a decrease in glucose concentration. This model mimics the major characteristics of obesity-associated human NIDDM as well as several stages of its progression, rendering it useful for studying the etiology of the metabolic and secretory defects in the syndrome.
Effect of lactate concentration and metabolic rate on net lactate uptake by canine skeletal muscle
Authors: Gladden L. B. , Crawford R. E. , Webster M. J.
Published: December 2017

This study addressed two questions: 1) Does net lactate uptake (L) by muscle approach a saturation limit with increasing blood lactate concentration ([La])? 2) Is the muscle net L response to increasing blood [La] affected by metabolic rate (VO2)? The gastrocnemius plantaris muscle group (GP) was isolated in situ in 20 anesthetized dogs. In three series of experiments, a lactate-lactic acid solution was infused into the arterial inflow of the GP to produce five different plasma [La] values: approximately 3, 9, 16, 22, and 30 mM, each of them maintained for 30 min. In one series, the GP remained at rest, whereas in the second series it contracted at 1 Hz and in the third series at 4 Hz. VO2 averaged approximately 3, 43, and 100 ml.kg-1.min-1 at rest and at 1 and 4 Hz, respectively. Within each of the three metabolic rates, increasing plasma [La] resulted in an increase in net L, which was well described (R > 0.98) by exponential equations. These equations predicted net L asymptotic values of 0.80, 0.72, and 1.09 mmol.kg-1.min-1 for rest and for 1 and 4 Hz, respectively. The corresponding plasma [La]s for half-maximal net L from the exponential equations were 16, 10, and 12 mM. Glucose uptake, pyruvate uptake/output, and alanine output by the muscles were not affected by the increasing [La] (and concomitant increases in net L) at any of the metabolic rates. Neither net glycogen synthesis nor depletion was changed by increasing [La].(ABSTRACT TRUNCATED AT 250 WORDS)
Immediate response to light of rat pineal melatonin rhythm: analysis by in vivo microdialysis
Authors: Kanematsu N. , Honma S. , Katsuno Y. , Honma K.
Published: December 2017

Melatonin in the extracellular space of the pineal gland was measured continuously for 4 consecutive days from single, freely moving rats by means of in vivo microdialysis. A robust circadian rhythm was observed in the pineal extracellular melatonin under both light-dark (LD) and continuous dark (DD) conditions, the patterns of which were almost identical for 4 days within individuals but varied substantially among individuals. The offset phase of melatonin rhythm was more stable than the onset phase. Light-induced phase shift of melatonin rhythm was measured in individual rats, which had been entrained to LD and subsequently released into DD. On the 1st day in DD, a 3-min light pulse of 200 lx was applied either at circadian time (CT) of 17 or 22 h (5 and 10 h after the dark onset, respectively). The light pulse rapidly suppressed the nocturnal melatonin level. The rate as well as the level of melatonin suppression was significantly greater by the pulse at CT22 than at CT17. A phase shift of the melatonin rhythm was calculated on the 2nd and 3rd days in DD. Significant phase delay shift was observed after the pulse at CT17 and advance shift after the pulse at CT22 of approximately 1 h in either case. Because the amount of phase shift was not different between the 2nd and 3rd days in DD, the phase shift of pineal melatonin rhythm by single light pulse seems to be completed immediately.
Ingestive patterns of liver-denervated rats presented with several diets
Authors: Bellinger L. L. , Dula G. , Williams F. E.
Published: December 2017

The liver by way of afferent nerves is suggested to be a controller of food intake. In experiment 1, male rats were given a 15% fructose solution during the first 4 h of the dark phase, while chow was available the rest of the time, for 10 days, before total liver denervation (TLD) or sham operation. Postsurgery ingestion patterns (15-min measurements for 4 h) of fructose were similar in the two groups. However, chow intake in the TLD group was slightly attenuated the first 2 days after surgery. In experiment 2, rats were given chow in cups and vegetable oil in bottles for 8 days before TLD or sham operation. After surgery, hourly ingestion of chow and oil did not differ between the groups; however, there was a trend for the TLD group to take more oil in the dark phase on the first-day diet exposure. In experiment 3, rats were fed a high-protein diet for 21 days before TLD or sham operation. With the use of a computer-operated system, postsurgery meal size, meal duration, and frequency patterns were found to be comparable between the groups. In experiment 4, rats were given a diet of sweetened condensed milk mixed with water (3:1 vol/vol) and vitamins for 14 days before hepatic vagal branch transection (HVBX) or sham operation. After surgery the first-day milk intake of both groups was similar up to 3.5 h and then depressed at 4 and 24 h in the HVBX rats, but was again comparable over the next 13 days; body weights were similar throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)