bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro metabolism by turtle heart mitochondria
Authors: Mersmann H. J. , Privitera C. A.
Published: December 2017

Both quantitative and qualitative aspects of the metabolic nature of heart mitochondria in the turtle, Chrysemys picta, have been investigated. Optimal in vitro incubation conditions for oxidative phosphorylation were approximated by alteration of the concentration of various components while using key substrates. The following has been established: exogenous cytochrome c is a necessary component; with an incubation volume of 2 ml the 2-µmole level of F– is the most suitable; 40 µmoles Pi is requisite for substrates metabolized at a high rate; 10 µmoles Mg++ is preferred with an initial ATP level of 3.2 µmoles. Succinate and malate were metabolized at similar rates (18 µmoles/mg N hr). Isocitrate was metabolized at about one-half this rate, whereas addition of NAD increased isocitrate oxidation to the succinate rate. α-Ketoglutarate was utilized at nearly 2.5 times the rate of succinate. Pyruvate oxidation (roughly one-third the succinate rate) increased about ninefold upon addition of 1 µmole malate. ß-Hydroxybutyrate was metabolized at the same rate as succinate. Addition of 1 µmole malate increased this rate nearly fivefold. Citrate apparently was not metabolized. Theoretical P/O ratios were approached with all metabolized substrates. Short-term starvation caused a decrease in both oxidation and phosphorylation. The capacity of turtle heart mitochondria to metabolize intermediates of the tricarboxylic acid cycle appears to be equivalent to that of mitochondria of mammalian cardiac muscle heretofore published.
Effect of intravenous volume infusion on heart rate in unanesthetized dogs
Authors: Hirsch L. J. , Boyd E. , Katz L. N.
Published: December 2017

Fifteen untrained, unanesthetized dogs were infused intravenously with blood for 10 min at the rate of 100 ml/min. The heart rate changes so induced were compared with the heart rate existing initially. Systemic arterial and venous pressures were also recorded by means of indwelling catheters. The direction of change in heart rate was found to depend on the initial heart rate. When the initial heart rate was below 120 beats/min the infusion caused a tachycardia; above this initial rate a bradycardia was induced. Denervation was carried out in 26 other dogs. Sympathectomy and "total" denervation of the heart tended to abolish the induced tachycardia, but not the induced bradycardia. Vagotomy did not abolish the induced bradycardia. In ten vagotomized dogs the initial rate was above 120 beats/min.
Ouabain-insensitive acidification by dopamine in renal OK cells: primary control of the Na+/H+exchanger
Authors: Gomes Pedro , Vieira-Coelho M. A. , Soares-da-Silva P.
Published: December 2017

The present study was aimed at evaluating the role of D1- and D2-like receptors and investigating whether inhibition of Na+transepithelial flux by dopamine is primarily dependent on inhibition of the apical Na+/H+exchanger, inhibition of the basolateral Na+-K+-ATPase, or both. The data presented here show that opossum kidney cells are endowed with D1- and D2-like receptors, the activation of the former, but not the latter, accompanied by stimulation of adenylyl cyclase (EC50= 220 ± 2 nM), marked intracellular acidification (IC50= 58 ± 2 nM), and attenuation of amphotericin B-induced decreases in short-circuit current (28.6 ± 4.5% reduction) without affecting intracellular pH recovery after CO2removal. These results agree with the view that dopamine, through the activation of D1- but not D2-like receptors, inhibits both the Na+/H+exchanger (0.001933 ± 0.000121 vs. 0.000887 ± 0.000073 pH unit/s) and Na+-K+-ATPase without interfering with the Na+-independent HCO[Formula: see text] transporter. It is concluded that dopamine, through the action of D1-like receptors, inhibits both the Na+/H+exchanger and Na+-K+-ATPase, but its marked acidifying effects result from inhibition of the Na+/H+exchanger only, without interfering with the Na+-independent HCO[Formula: see text] transporter and Na+-K+-ATPase.
Lengthening contractions are not required to induce protection from contraction-induced muscle injury
Authors: Koh Timothy J. , Brooks Susan V.
Published: December 2017

We tested the hypothesis that lengthening contractions and subsequent muscle fiber degeneration and/or regeneration are required to induce exercise-associated protection from lengthening contraction-induced muscle injury. Extensor digitorum longus muscles in anesthetized mice were exposed in situ to repeated lengthening contractions, isometric contractions, or passive stretches. Three days after lengthening contractions, maximum isometric force production was decreased by 55%, and muscle cross sections contained a significant percentage (18%) of injured fibers. Neither isometric contractions nor passive stretches induced a deficit in maximum isometric force or a significant number of injured fibers at 3 days. Two weeks after an initial bout of lengthening contractions, a second identical bout produced a force deficit (19%) and a percentage of injured fibers (5%) that was smaller than those for the initial bout. Isometric contractions and passive stretches also provided protection from lengthening contraction-induced injury 2 wk later (force deficits = 35 and 36%, percentage of injured fibers = 12 and 10%, respectively), although the protection was less than that provided by lengthening contractions. These data indicate that lengthening contractions and fiber degeneration and/or regeneration are not required to induce protection from lengthening contraction-induced injury.
Phenanthraquinone inhibits eNOS activity and suppresses vasorelaxation
Authors: Kumagai Yoshito , Hayashi Toshio , Miyauchi Takashi , Endo Akiko , Iguchi Akihisa , Kiriya-Sakai Minako , Sakai Satoshi , Yuki Koichi , Kikushima Makoto , Shimojo Nobuhiro
Published: December 2017

Diesel exhaust particles cause an impairment of endothelium-dependent vasorelaxation and are associated with cardiopulmonary-related diseases and mortality, but the mechanistic details are poorly understood. Since we reported previously that phenanthraquinone, an environmental chemical contained in diesel exhaust particles, suppresses neuronal nitric oxide synthase (nNOS) activity by shunting electrons away from the normal catalytic pathway, it was hypothesized that phenanthraquinone inhibits endothelial NOS (eNOS) activity and affects vascular tone. Therefore, the effects of phenanthraquinone on eNOS activity, endothelium-dependent relaxation, and blood pressure were examined in the present study. Phenanthraquinone inhibited NO formation evaluated by citrulline formed by total membrane fraction of bovine aortic endothelial cells with an IC50 value of 0.6 μM. A kinetic study revealed that phenanthraquinone is a competitive inhibitor with respect to NADPH and a noncompetitive inhibitor with respect to l-arginine. Endothelium-dependent relaxation of rat aortic rings by ACh was significantly inhibited by phenanthraquinone (5 μM), whereas the endothelium-independent relaxation by nitroglycerin was not. Furthermore, an intraperitoneal injection of phenanthraquinone (0.36 mmol/kg) to rats resulted in an elevation of blood pressure (1.4-fold, P < 0.01); under this condition, plasma levels of stable NO metabolites, nitrite/nitrate, in phenanthraquinone-treated rats was reduced to 68% of control levels. The present findings suggest that phenanthraquinone has a potent inhibitory action on eNOS activity via a similar mechanism reported for nNOS, thereby causing the suppression of NO-mediated vasorelaxation and elevation of blood pressure.
A role for NPY overexpression in the dorsomedial hypothalamus in hyperphagia and obesity of OLETF rats
Authors: Bi Sheng , Ladenheim Ellen E. , Schwartz Gary J. , Moran Timothy H.
Published: December 2017

Otsuka Long-Evans Tokushima Fatty (OLETF) rats lacking CCK-A receptors are hyperphagic, obese, and diabetic. We have previously demonstrated that these rats have a peripheral satiety deficit resulting in increased meal size. To examine the potential role of hypothalamic pathways in the hyperphagia and obesity of OLETF rats, we compared patterns of hypothalamic neuropeptide Y (NPY), proopiomelanocortin (POMC), and leptin receptor mRNA expression in ad libitum-fed Long-Evans Tokushima (LETO) and OLETF rats and food-restricted OLETF rats that were pair-fed to the intake of LETO controls. Pair feeding OLETF rats prevented their increased body weight and elevated levels of plasma insulin and leptin and normalized their elevated POMC and decreased NPY mRNA expression in the arcuate nucleus. In contrast, NPY expression was upregulated in the dorsomedial hypothalamus (DMH) in pair-fed OLETF rats. A similar DMH NPY overexpression was evident in 5-wk-old preobese OLETF rats. These findings suggest a role for DMH NPY upregulation in the etiology of OLETF hyperphagia and obesity.
Hemodynamic response pattern predicts susceptibility to stress-induced elevation in arterial pressure in the rat
Authors: Muller Jay R. , Le Khoi M. , Haines William R. , Gan Qi , Knuepfer Mark M.
Published: December 2017

Cocaine or air jet stress evokes pressor responses due to either a large increase in systemic vascular resistance (vascular responders) or small increases in both cardiac output and vascular resistance (mixed responders) in conscious rats. Repeated cocaine administration results in elevated arterial pressure in vascular responders but not in mixed responders. The present study examined the hypothesis that the pattern of cardiovascular responses to an unconditioned stimulus (UCS; air jet) is related to responses to a conditioned stimulus (CS; tone followed by brief foot shock) in individual rats. Our data demonstrate that presentation of the UCS produced variable cardiac output responses that correlated with responses to the CS ( n = 60). We also determined whether individual cardiovascular response patterns to acute stress correlated with predisposition to a sustained stress-induced elevation in arterial pressure. Rats were exposed to three different stressors presented one per day successively for 4 wk and during a poststress period of 3 wk while arterial pressure was recorded periodically. Mean arterial pressure was elevated in all rats during chronic stress but, during the poststress period, remained at significantly higher levels in vascular responders but not mixed responders. Therefore, we conclude that acute behavioral stress to a conditioned stimulus elicits variable hemodynamic responses that predict the predisposition to a sustained stress-induced elevation in arterial pressure.
Effect of nitric oxide in the nucleus isthmi on the hypoxic and hypercarbic drive to breathing of toads
Authors: Gargaglioni Luciane H. , Branco Luiz G. S.
Published: December 2017

Nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain that has been reported to participate in CO2chemoreception and in the ventilatory response to hypoxia. However, no information exists about the modulators and/or mediators involved. In the present study, we assessed the participation of nitric oxide (NO) in the hypoxic and hypercarbic drive to breathing, specifically in the NI. We compared the ventilatory and cardiovascular responses with hypoxia and hypercarbia after microinjecting 100 nmol/0.5 μl of NG-nitro-l-arginine methyl ester (l-NAME; an NO synthase blocker) into the NI of toads ( Bufo paracnemis). l-NAME had no effect under resting conditions. Hypoxia elicited an increase in ventilation in control and vehicle toads by elevating tidal volume (VT). Hypercarbia caused hyperventilation in all groups due to an increase in both VTand frequency. The microinjection ofl-NAME into the NI elicited an increase in ventilatory response to hypoxia and hypercarbia due to a higher VT.We conclude that NO in the NI has an inhibitory effect when the respiratory drive is high, acting on VT.
Denervation enhances the physiological effects of the KATP channel during fatigue in EDL and soleus muscle
Authors: Matar W. , Lunde J. A. , Jasmin B. J. , Renaud J.-M.
Published: December 2017

The objective was to determine whether denervation reduces or enhances the physiological effects of the KATP channel during fatigue in mouse extensor digitorum longus (EDL) and soleus muscle. For this, we measured the effects of 100 μM of pinacidil, a channel opener, and of 10 μM of glibenclamide, a channel blocker, in denervated muscles and compared the data to those observed in innervated muscles from the study of Matar et al. (Matar W, Nosek TM, Wong D, and Renaud JM. Pinacidil suppresses contractility and preserves energy but glibenclamide has no effect during fatigue in skeletal muscle. Am J Physiol Cell Physiol 278: C404–C416, 2000). Pinacidil increased the 86Rb+ fractional loss during fatigue, and this effect was 2.6- to 3.4-fold greater in denervated than innervated muscle. Pinacidil also increased the rate of fatigue; for EDL the effect was 2.5-fold greater in denervated than innervated muscle, whereas for soleus the difference was 8.6-fold. A major effect of glibenclamide was an increase in resting tension during fatigue, which was for the EDL and soleus muscle 2.7- and 1.9-fold greater, respectively, in denervated than innervated muscle. A second major effect of glibenclamide was a reduced capacity to recover force after fatigue, an effect observed only in denervated muscle. We therefore suggest that the physiological effects of the KATP channel are enhanced after denervation.
Intracellular monocyte and serum cytokine expression is modulated by exhausting exercise and cold exposure
Authors: Rhind Shawn G. , Castellani John W. , Brenner Ingrid K. M. , Shephard Roy J. , Zamecnik Jiri , Montain Scott J. , Young Andrew J. , Shek Pang N.
Published: December 2017

This study tested the hypothesis that exercise elicits monocytic cytokine expression and that prolonged cold exposure modulates such responses. Nine men (age, 24.6 ± 3.8 y; V˙o 2 peak, 56.8 ± 5.6 ml · kg−1 · min−1) completed 7 days of exhausting exercise (aerobic, anaerobic, resistive) and underwent three cold, wet exposures (CW). CW trials comprised ≤6 h (six 1-h rest-work cycles) exposure to cold (5°C, 20 km/h wind) and wet (5 cm/h rain) conditions. Blood samples for the determination of intracellular and serum cytokine levels and circulating hormone concentrations were drawn at rest (0700), after exercise (∼1130), and after CW (∼2000). Whole blood was incubated with (stimulated) or without (spontaneous) lipopolysaccharide (LPS; 1 μg/ml) and stained for CD14 monocyte surface antigens. Cell suspensions were stained for intracellular cytokine expression and analyzed by flow cytometry. The proportion of CD14+ monocytes exhibiting spontaneous and stimulated intracellular expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α increased after exercise, but these cells produced less IL-1β and TNF-α after CW when CW was preceded by exhausting exercise. Serum cytokine concentrations followed a parallel trend. These findings suggest that blood monocytes contribute to exercise-induced cytokinemia and that cold exposure can differentially modulate cytokine production, upregulating expression of IL-6 and IL-1 receptor antagonist but downregulating IL-1β and TNF-α. The cold-induced changes in cytokine expression appear to be linked to enhanced catecholamine secretion associated with cold exposure.
N-acetyl-l-cysteine improves renal medullary hypoperfusion in acute renal failure
Authors: Conesa Erica López , Valero Fernando , Nadal José Carlos , Fenoy Francisco J. , López Bernardo , Arregui Begoña , Salom Miguel García
Published: December 2017

This study evaluated the effects of N-acetyl-l-cysteine (NAC), a free radical scavenger, and Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide (NO) synthesis inhibitor, on the changes in renal function, intrarenal blood flow distribution (laser-Doppler flowmetry), and plasma peroxynitrite levels during the acute renal failure (ARF) produced by inferior vena cava occlusion (IVCO; 45 min) in anesthetized rats. Renal blood flow fell on reperfusion (whole kidney by −45.7%; cortex −58.7%, outer medulla −62.8%, and papilla −47.7%); glomerular filtration rate (GRF) also decreased (−68.6%), whereas fractional sodium excretion (FENa%) and peroxynitrite and NO[Formula: see text]/NO[Formula: see text] plasma levels increased (189.5, 46.5, and 390%, respectively) after ischemia. Pretreatment with l-NAME (10 μg · kg−1· min−1) aggravated the fall in renal blood flow seen during reperfusion (−60%). Pretreatment with NAC (150 mg/kg bolus + 715 μg · kg−1· min−1iv) partially prevented those changes in renal function (GFR only fell by −29.2%, and FENa%increased 119.4%) and laser-Doppler blood flow, especially in the outer medulla, where blood flow recovered to near control levels during reperfusion. These beneficial effects seen in rats given NAC seem to be dependent on the presence of NO, because they were abolished in rats pretreated with l-NAME. Also, the antioxidant effects of NAC prevented the increase in plasma peroxynitrite after ischemia. In conclusion, NAC ameliorates the renal failure and the outer medullary vasoconstriction induced by ICVO, effects that seem to be dependent on the presence of NO and the scavenging of peroxynitrite.
Interleukin-18 promotes sleep in rabbits and rats
Authors: Kubota Takeshi , Fang Jidong , Brown Richard A. , Krueger James M.
Published: December 2017

Interleukin (IL)-1β is involved in physiological sleep regulation. IL-18 is a member of the IL-1 family, and its signal-transduction mechanism is similar to that of IL-1. Therefore, we hypothesized that IL-18 might also be involved in sleep regulation. Three doses of IL-18 (10, 100, and 500 ng) were injected intracerebroventricularly (icv) into rabbits at the onset of the dark period. The two higher doses of IL-18 markedly increased non-rapid eye movement sleep (NREMS), accompanied by increases in brain temperature (Tbr). These effects were lost after the heat inactivation of IL-18. The 500 ng of IL-18 injection during the light period also increased NREMS and Tbr. Similar results were obtained after icv injection of 100 ng of IL-18 into rats. Furthermore, intraperitoneal injection of 30 μg/kg of IL-18 slightly, but significantly, increased NREMS, whereas it significantly decreased electroencephalogram slow-wave activity in rats. Intraperitoneal IL-18 failed to induce fever. An anti-human IL-18 antibody had little effect on spontaneous sleep in rabbits, although the anti-IL-18 antibody significantly attenuated muramyl dipeptide-induced sleep. These data suggest that IL-18 is involved in mechanisms of sleep responses to infection.
Conditions that affect sleep alter the expression of molecules associated with synaptic plasticity
Authors: Taishi P. , Sanchez C. , Wang Y. , Fang J. , Harding J. W. , Krueger J. M.
Published: December 2017

Many theories propose that sleep serves a purpose in synaptic plasticity. We tested the hypothesis, therefore, that manipulation of sleep would affect the expression of molecules known to be involved in synaptic plasticity. mRNA expression of four molecules [brain-derived neurotrophic factor (BDNF), activity-regulated cytoskeleton-associated protein (Arc), matrix metalloproteinase-9 (MMP-9), and tissue plasminogen activator (tPA)] was determined after 8 h of sleep deprivation and after 6 h of a mild increase in ambient temperature, a condition that enhances sleep in rats. After sleep deprivation, BDNF, Arc, and tPA mRNAs in the cerebral cortex increased while MMP-9 mRNA levels decreased. Conversely, after enhanced ambient temperature, BDNF, Arc, and tPA mRNAs decreased while MMP-9 mRNA increased. In the hippocampus, sleep deprivation did not significantly affect BDNF and tPA expression, although Arc mRNA increased and MMP-9 mRNA decreased. Brain temperature enhancement decreased Arc mRNA levels in the hippocampus but did not affect BDNF, MMP-9, or tPA in this area. Results are consistent with the notion that sleep plays a role in synaptic plasticity.
Effect of nicotine on vasoconstrictor and vasodilator responses in human skin vasculature
Authors: Black Claire E. , Huang Ning , Neligan Peter C. , Levine Ronald H. , Lipa Joan E. , Lintlop Steven , Forrest Christopher R. , Pang Cho Y.
Published: December 2017

Our objective was to test the hypothesis that acute exposure of human skin vasculature to nicotine may have deleterious effects on endothelial function. Vasoconstriction and vasorelaxation in isolated perfused human skin flaps (∼8 × 18 cm) derived from dermolipectomy specimens were assessed by studying changes in skin perfusion pressure measured by a pressure transducer, and skin perfusion was assessed by a dermofluorometry technique ( n = 4 or 5). It was observed that nicotine (10−7M) amplified ( P < 0.05) the norepinephrine (NE)-induced concentration-dependent (10−7-10−5M) increase in skin vasoconstriction compared with the control. This amplification effect of nicotine in NE-induced skin vasoconstriction was not blocked by the nicotine-receptor antagonist hexamethonium (10−6M) or the cyclooxygenase inhibitor indomethacin (10−5M). It was also observed that ACh and nitroglycerin (NTG) elicited a concentration-dependent (10−8-10−5M) vasorelaxation in skin flaps preconstricted with 8 × 10−7M of NE. The vasorelaxation induced by ACh was attenuated ( P < 0.05) in the presence of nicotine (10−7M) compared with the control. However, skin vasorelaxation induced by NTG was not affected by nicotine (10−7M). ACh and NTG are known to induce endothelium-dependent and -independent vasorelaxation, respectively. The present findings were interpreted to indicate that acute exposure of human skin vasculature to nicotine was associated with 1) amplification of NE-induced skin vasoconstriction and 2) impairment of endothelium-dependent skin vasorelaxation. Cyclooxygenase products and nicotine receptors blocked by hexamethonium were not involved in the amplification of NE-induced skin vasoconstriction by nicotine. These findings may provide further insight into the pathogenesis of skin vasospasm in skin flap surgery and skin ischemic disease associated with cigarette smoking or use of smokeless tobacco.
Potentiation of glutamatergic synaptic input to supraoptic neurons by presynaptic nicotinic receptors
Authors: Li De-Pei , Pan Hui-Lin
Published: December 2017

The release of vasopressin and oxytocin from the supraoptic nucleus (SON) neurons is tonically regulated by excitatory glutamatergic and inhibitory GABAergic synaptic inputs. Acetylcholine is known to excite SON neurons and to elicit vasopressin release. Cholinergic receptors are located pre- and postsynaptically in the SON, but their functional significance in the regulation of SON neurons is not fully understood. In this study, we determined the role of presynaptic cholinergic receptors in regulation of the excitatory glutamatergic inputs to the SON neurons. The magnocellular neurons in the rat hypothalamic slices were identified microscopically, and the spontaneous miniature excitatory postsynaptic currents (mEPSCs) were recorded using the whole cell voltage-clamp technique. The mEPSCs were abolished by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM). Acetylcholine (100 μM) significantly increased the frequency of mEPSCs of 38 SON neurons from 1.87 ± 0.36 to 3.42 ± 0.54 Hz but did not alter the amplitude (from 19.61 ± 0.90 to 19.34 ± 0.84 pA) and the decay time constant of mEPSCs. Furthermore, the nicotinic receptor antagonist mecamylamine (10 μM, n= 16), but not the muscarinic receptor antagonist atropine (100 μM, n = 12), abolished the excitatory effect of acetylcholine on the frequency of mEPSCs. These data provide new information that the excitatory effect of acetylcholine on the SON neurons is mediated, at least in part, by its effect on presynaptic glutamate release. Activation of presynaptic nicotinic, but not muscarinic, receptors located in the glutamatergic terminals increases the excitatory synaptic input to the SON neurons of the hypothalamus.
Static handgrip exercise modifies arterial baroreflex control of vascular sympathetic outflow in humans
Authors: Kamiya Atsunori , Michikami Daisaku , Fu Qi , Niimi Yuki , Iwase Satoshi , Mano Tadaaki , Suzumura Akio
Published: December 2017

To examine effects of static exercise on the arterial baroreflex control of vascular sympathetic nerve activity, 22 healthy male volunteers performed 2 min of static handgrip exercise at 30% of maximal voluntary force, followed by postexercise circulatory arrest (PE-CA). Microneurographic recording of muscle sympathetic nerve activity (MSNA) was made with simultaneous recording of arterial pressure (Portapres). The relationship between MSNA and diastolic arterial pressure was calculated for each condition and was defined as the arterial baroreflex function. There was a close relationship between MSNA and diastolic arterial pressure in each subject at rest and during static exercise and PE-CA. The slope of the relationship significantly increased by >300% during static exercise ( P < 0.001), and the x-axis intercept (diastolic arterial pressure level) increased by 13 mmHg during exercise ( P< 0.001). These alterations in the baroreflex relationship were completely maintained during PE-CA. It is concluded that static handgrip exercise is associated with a resetting of the operating range and an increase in the reflex gain of the arterial barorelex control of MSNA.
Gastric negative feedback produced by volume and nutrient during a meal in rats
Authors: Eisen Susanne , Davis John D. , Rauhofer Ellen , Smith Gerard P.
Published: December 2017

To investigate the gastric negative-feedback control of eating during a meal, we implanted male rats with pyloric cuffs and gastric catheters and gave them access to sweet milk for 30 min after overnight deprivation. Ingested milk and infused milk or saline were confined to the stomach because the pyloric cuffs were closed in all tests. Rats received five consecutive tests with no gastric infusion or with infusions of 3, 6, or 12 ml of milk or saline during the first 6 min of the test meal. Only 12-ml infusions decreased intake significantly compared with no infusion. Because 12 ml of saline inhibited intake as much as 12 ml of milk, the decreased intake was due to volume or rate of infusion, not nutrient. Although infusions of 3 and 6 ml of milk did not decrease intake, they decreased the number of licks after the infusions significantly more than equal volumes of saline. Thus a large volume or rapid rate of gastric infusion decreases intake, and some other aspect of small milk infusions decreases the rate of licking.
Histamine H1 receptors mediate the anorectic action of the pancreatic hormone amylin
Authors: Mollet A. , Lutz T. A. , Meier S. , Riediger T. , Rushing P. A. , Scharrer E.
Published: December 2017

We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperitoneally injected amylin (5 and 20 μg/kg), the amylin agonist salmon calcitonin (sCT; 10 μg/kg), leptin (1.3 mg/kg), and cholecystokinin (CCK; 20 μg/kg). The experiments were performed with mice lacking functional H1 receptors (H1Rko) and wild-type (WT) controls. The mice were also injected with the H3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through presynaptic H3 receptors. The feeding-suppressive effect of thioperamide was abolished in H1Rko mice. The anorectic effects of amylin and sCT were significantly reduced in 12-h food-deprived H1Rko mice compared with WT mice [1-h food intake: WT-NaCl 0.51 ± 0.05 g vs. WT-amylin (5 μg/kg) 0.30 ± 0.06 g ( P < 0.01); H1Rko-NaCl 0.45 ± 0.05 g vs. H1Rko-amylin 0.40 ± 0.04 g; WT-NaCl 0.40 ± 0.09 g vs. WT-sCT (10 μg/kg) 0.14 ± 0.10 g ( P < 0.05); H1Rko-NaCl 0.44 ± 0.08 g vs. H1Rko-sCT 0.50 ± 0.06 g]. The anorectic effect of leptin was absent in ad libitum-fed H1Rko mice, whereas CCK equally reduced feeding in WT and H1Rko animals. This suggests that the histaminergic system is involved in mediating the anorectic effects of peripheral amylin and sCT via histamine H1 receptors. The same applies to leptin but not to CCK. H1Rko mice showed significantly increased body weight gain compared with WT mice, supporting the role of endogenous histamine in the regulation of feeding and body weight.
Delayed puberty and response to testosterone in a rat model of colitis
Authors: Azooz Omiea G. , Farthing Michael J. G. , Savage Martin O. , Ballinger Anne B.
Published: December 2017

Delayed puberty is a frequent complication of inflammatory bowel disease. The precise etiological mechanisms are not known. In this study, we wanted to determine the relative contribution of undernutrition and inflammation to delayed puberty and the effect of inflammation on the reproductive axis. Puberty was assessed in rats with 2,4,6-trinitrobenzenesulfonic acid induced-colitis, healthy controls, and animals pair fed to match the food intake of the colitic group. The response to testosterone administration was assessed in colitic rats. We found that induction of colitis was associated with hypophagia and reduced weight gain, and undernutrition in healthy females (i.e., pair fed) resulted in a delay in the onset (by 4.8 days, P < 0.001) and progression of puberty (normal estrous cycles in 42%, P = 0.04) compared with controls. However, puberty was further delayed in the colitic group (1.4 days after pair fed) with the absence of normal estrous cycling in all rats. In males, the onset of puberty was also delayed, and weights of accessory sex organs were reduced compared with pair-fed controls. Plasma testosterone concentrations were low, and gonadotropin concentrations were normal in colitic rats. Testosterone treatment normalized puberty in male rats with colitis. In conclusion, in rats with experimental colitis, inflammation appears to potentiate the effect of undernutrition on puberty. The weights of secondary sex organs and the onset of puberty were normalized by testosterone treatment.
Direct innervation of white fat and adrenal medullary catecholamines mediate photoperiodic changes in body fat
Authors: Demas Gregory E. , Bartness Timothy J.
Published: December 2017

Seasonal adjustments in Siberian hamster adiposity are triggered by day length changes [i.e., short “winter-like” days (SDs) elicit body fat decreases vs. long “summer-like” days (LDs)]. These and other white adipose tissue (WAT) mass decreases traditionally have been ascribed to lipolysis triggered by sympathetically mediated, adrenal medullary released epinephrine; however, recent evidence suggests that direct sympathetic innervation of WAT also is important. Therefore, the contributions of WAT sympathetic innervation and adrenal medullary catecholamines to SD-induced decreases in adiposity were tested. Siberian hamsters were surgically bilaterally adrenal demedullated (ADMEDx) or sham ADMEDx, and all had one inguinal WAT (IWAT) pad sympathectomized via locally injected guanethidine, with the contralateral pad serving as a within-animal innervated control. One-half of the hamsters remained in LDs; the remainder was transferred to SDs. Guanethidine and ADMEDx abolished IWAT norepinephrine and adrenal epinephrine contents, respectively. Although sympathetic denervation or ADMEDx alone did not block SD-induced decreases in IWAT mass, their combination did. These results suggest that both adrenal catecholamines and the sympathetic innervation of WAT interact to decrease SD-induced decreased adiposity.
Intracellular and extracellular calcium utilization during hypoxic vasoconstriction of cyclostome aortas
Authors: Russell Michael J. , Pelaez Nancy J. , Packer C. Subah , Forster Malcom E. , Olson Kenneth R.
Published: December 2017

Hypoxic vasoconstriction (HV) is an intrinsic response of mammalian pulmonary and cyclostome aortic vascular smooth muscle. The present study examined the utilization of calcium during HV in dorsal aortas (DA) from sea lamprey and New Zealand hagfish. HV was temporally correlated with increased free cytosolic calcium (Ca[Formula: see text]) in lamprey DA. Extracellular calcium (Ca[Formula: see text]) did not contribute significantly to HV in lamprey DA, but it accounted for 38.1 ± 5.3% of HV in hagfish DA. Treatment of lamprey DA with ionomycin, ryanodine, or caffeine added to thapsigargin-reduced HV, whereas HV was augmented by BAY K 8644. Methoxyverapamil (D600) in zero Ca[Formula: see text] did not affect HV in lamprey DA, nor did it prevent further constriction when Ca[Formula: see text] was restored during hypoxia in hagfish DA. Removal of extracellular sodium (Na[Formula: see text]) caused a constriction in both species. Lamprey DA relaxed to prehypoxic tension following return to normoxia in zero Na[Formula: see text], whereas relaxation was inhibited in hagfish DA. Relaxation following HV was inhibited in lamprey DA when Na[Formula: see text] and Ca[Formula: see text] were removed. These results show that HV is correlated with [Ca2+]cin lamprey DA and that Na+/Ca2+exchange is used during HV in hagfish but not lamprey DA. Multiple receptor types appear to mediate stored intracellular calcium release in lamprey DA, and L-type calcium channels do not contribute significantly to constriction in either cyclostome.
AT1-receptor blockade in the hypothalamic PVN reduces central hyperosmolality-induced renal sympathoexcitation
Authors: Chen Qing Hui , Toney Glenn M.
Published: December 2017

Autonomic neurons in the hypothalamic paraventricular nucleus (PVN) are innervated by osmotic-sensitive regions of the lamina terminalis, receive input from ANG II-containing cells, and express AT1 ANG II receptors. Therefore, we hypothesized that ANG II actions within the PVN could underlie hyperosmolality-induced increases in renal sympathetic nerve activity (RSNA). In anesthetized baroreceptor-denervated rats, graded concentrations of NaCl (0.30, 0.9, 1.5, and 2.1 osmol/l) were injected (300 μl) centrally via the internal carotid artery (ICA) and produced corresponding increases in mean arterial pressure (MAP) and RSNA. In addition, equivalent hyperosmotic loads (1.5 osmol/l) of NaCl, glucose, and mannitol each significantly ( P < 0.05) increased MAP and RSNA. The same stimuli had no effect when administered intravenously. Bilateral PVN microinjections (100 nl) of the AT1-receptor antagonist losartan (80 nmol) before osmotic challenge had no effect on resting RSNA but significantly ( P < 0.05) reduced RSNA responses to hyperosmotic NaCl ( n = 7), glucose ( n = 6), and mannitol ( n = 6). Increases in RSNA evoked by hyperosmotic NaCl were significantly ( P < 0.05) attenuated ∼20 min after losartan injection and recovered within 60–120 min. In contrast, losartan outside the PVN as well as vehicle (saline) within the PVN failed to alter RSNA responses to ICA hyperosmotic NaCl. Results suggest that elevated RSNA after central sodium/osmotic activation is mediated, at least in part, by a synaptic mechanism involving AT1-receptor activation within the PVN.
Developmental changes in intracellular pH regulation in medullary neurons of the rat
Authors: Nottingham S. , Leiter J. C. , Wages P. , Buhay S. , Erlichman J. S.
Published: December 2017

We examined intracellular pH (pHi) regulation in the retrotrapezoid nucleus (RTN), a CO2-sensitive site, and the hypoglossal nucleus, a nonchemosensitive site, during development (postnatal days 2–18) in rats. Respiratory acidosis [10% CO2, extracellular pH (pHo) 7.18] caused acidification without pHirecovery in the RTN at all ages. In the hypoglossal nucleus, pHirecovered in young animals, but as animal age increased, the slope of pHirecovery diminished. In animals older than postnatal day 11, the pHiresponses to hypercapnia were identical in the hypoglossal nucleus and the RTN, but hypoglossal nucleus and RTN neurons could regulate pHiduring intracellular acidification at constant pHoat all ages. Recovery of pHifrom acidification in the RTN depended on extracellular Na+and was inhibited by amiloride but was unaffected by DIDS, suggesting a role for Na+/H+exchange. Hence, pHiregulation during acidosis is more effective in the hypoglossal nucleus in younger animals, possibly as a requirement of development, but in older juvenile animals (older than postnatal day 11), pHiregulation is relatively poor in chemosensitive (RTN) and nonchemosensitive nuclei (hypoglossal nucleus).
Angiotensin II in cardiac pressure-overload hypertrophy in fetal sheep
Authors: Segar Jeffrey L. , Dalshaug Gregory B. , Bedell Kurt A. , Smith Oliva M. , Scholz Thomas D.
Published: December 2017

We previously demonstrated in fetal sheep that blockade of ANG II type 1 (AT1) receptors did not attenuate an increase in right ventricle (RV) mass resulting from partial occlusion of the pulmonary artery (PA). We have now determined the effects of AT2-receptor blockade (PD-123319, 10 mg · kg−1· day−1continuous iv) on the response of the fetal RV to PA banding for 7 days. Four groups of fetuses (each n = 7) were studied beginning at 126 ± 1 days gestation (term 145 days). RV weight-to-body weight ratio (RV wt/body wt) increased ( P < 0.05) in PA-banded (6.00 ± 0.09 g/kg) and PA-banded + PD-123319 (6.19 ± 0.27 g/kg) compared with control (5.17 ± 0.17 g/kg) and PD-123319-infused (5.27 ± 0.35 g/kg) fetuses (means ± SE). Blood pressure and heart rate were similar in all groups. PD-123319 produced a decrease ( P < 0.05) in AT1but not AT2mRNA levels in both fetal ventricles. To examine the effect of ANG II on fetal heart growth, twin fetal sheep were infused with either ANG II (twin received vehicle) or phenylephrine (Phe) (twin received vehicle) continuously for 7 days. Mean arterial blood pressure was 20–25 mmHg higher in ANG II and Phe fetuses compared with controls. The rate-pressure product was similar in ANG II and Phe fetuses and 40–50% greater than controls. Phe resulted in no change in RV wt/body wt or left ventricle-to-body weight ratio (LV wt/body wt) compared with controls. In contrast, ANG II produced a selective increase (27 ± 5%, P < 0.05) in LV wt/body wt; no effect was seen on the RV. ANG II produced a decrease ( P < 0.05) in LV but not RV AT1mRNA levels compared with controls; no effect was seen with Phe. The data demonstrate that in the ovine fetus, AT2receptors do not contribute to the maintenance of blood pressure or the development of pressure-overload RV hypertrophy. Elevated ANG II levels produce a selective increase in LV mass in the fetal sheep that is, in part, independent of increased systolic load.
Enhanced pyruvate dehydrogenase activity does not affect muscle O2uptake at onset of intense exercise in humans
Authors: Bangsbo Jens , Gibala Martin J. , Krustrup Peter , González-Alonso José , Saltin Bengt
Published: December 2017

It has been proposed that the activation state of pyruvate dehydrogenase (PDH) may influence the rate of skeletal muscle O2uptake during the initial phase of exercise; however, this has not been directly tested in humans. To remedy this, we used dichloroacetate (DCA) infusion to increase the active form of PDH (PDHa) and, subsequently, measured leg O2uptake and markers of anaerobic ATP provision during conditions of intense dynamic exercise, when the rate of muscle O2uptake would be very high. Six subjects performed brief bouts of one-legged knee-extensor exercise at ∼110% of thigh peak O2uptake (65.3 ± 3.7 W) on several occasions: under noninfused control (Con) and DCA-supplemented conditions. Needle biopsy samples from the vastus lateralis muscle were obtained at rest and after 5 s, 15 s, and 3 min of exercise during both experimental conditions. In addition, thigh blood flow and femoral arteriovenous differences for O2and lactate were measured repeatedly during the 3-min work bouts (Con and DCA) to calculate thigh O2uptake and lactate release. After DCA administration, PDHawas four- to eightfold higher ( P < 0.05) than Con at rest, and PDHaremained ∼130% and 100% higher ( P< 0.05) after 5 and 15 s of exercise, respectively. There was no difference between trials after 3 min. Despite the marked difference in PDHabetween trials at rest and during the initial phase of exercise, thigh O2uptake was the same. In addition, muscle phosphocreatine utilization and lactate production were similar after 5 s, 15 s, and 3 min of exercise in DCA and Con. The present findings demonstrate that increasing PDHadoes not alter muscle O2uptake and anaerobic ATP provision during the initial phase of intense dynamic knee-extensor exercise in humans.
Increased coronary blood flow signals growth of coronary resistance vessels in near-term ovine fetuses
Authors: Wothe D. , Hohimer A. , Morton M. , Thornburg K. , Giraud G. , Davis L.
Published: December 2017

We measured maximal coronary artery conductance in near-term fetal sheep before and after chronic infusion with adenosine to determine whether an increase in coronary flow without hypoxemia results in increased coronary vascular growth. Adenosine was infused into the circumflex coronary artery for 12 h each day for 4 days. Coronary flow was maintained at double the resting level by regulating the infusion of adenosine via a computerized servocontrol device signaled by a Doppler flow-velocity sensor. Total arterial hemoglobin, oxygen content, and hemodynamics were unchanged. Resting circumflex coronary blood flow increased from control of 250 ± 111 to 530 ± 216 ml · min−1 · 100 g left ventricle−1 with adenosine on day 1 and from 194 ± 74 to 878 ± 210 ml · min−1 · 100 g left ventricle−1 with adenosine on the last day ( P < 0.01). Coronary conductance, determined during maximal vasodilation, increased from 14.0 ± 5.0 to 26.9 ± 3.9 ml · min−1 · 100 g−1 · mmHg−1 over the 4 days ( P < 0.001). Coronary flow reserve, the difference between resting and maximal myocardial blood flow interpolated at 40 mmHg, increased from 299 ± 196 to 672 ± 266 ml · min−1 · 100 g−1( P < 0.001). Maximal coronary conductance was unchanged in control saline-infused fetuses (18.5 ± 5.1 vs. 18.5 ± 8.7 ml · min−1 · 100 g−1 · mmHg−1). We conclude that chronic intracoronary adenosine administration to the fetal myocardium modulates coronary vascular growth, even in the absence of tissue hypoxia.
Renal 20-hydroxyeicosatetraenoic acid synthesis during pregnancy
Authors: Wang Mong-Heng , Zand Barbara A. , Nasjletti Alberto , Laniado-Schwartzman Michal
Published: December 2017

We examined whether renal 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis is altered during gestation. Renal microsomal arachidonic acid ω-hydroxylase activity increased by 50 and 48% in rats on days 12 and 19 of gestation, respectively. Renal microvessel 20-HETE synthesis increased by 50 and 82% in rats on days 6 and 12 of gestation, respectively, and returned to control levels at day 19 of gestation. In contrast, 20-HETE synthesis in isolated medullary thick ascending limb was unchanged from control levels on days 6and 12 of gestation, but it increased twofold on day 19 of gestation. This increase on day 19 of gestation was associated with a twofold increase in urinary 20-HETE excretion, and it coincided with a 23-mmHg fall in blood pressure. Moreover, change in the rate of 20-HETE synthesis in microvessels was consistent with the level of expression of cytochrome P450 (CYP)4A proteins. Administration of the CYP4A inhibitor 1-aminobenzotriazole (ABT) for 2 days on day 12 of pregnancy or for 5 days starting on day 15 of pregnancy caused a transient but significant reduction in systolic blood pressure. ABT treatment also decreased urinary sodium, urinary 20-HETE, and renal and microvessel 20-HETE synthesis. This study, to our knowledge, is the first to demonstrate that 20-HETE synthesis in the kidney is altered in time- and site-specific manners during pregnancy. The localized pattern of changes suggests that there are distinct regulatory mechanisms for 20-HETE synthesis in the kidney during pregnancy.
Ventilatory thresholds during short- and long-term exercise
Authors: Reybrouck T. , Ghesquiere J. , Cattaert A. , Fagard R. , Amery A.
Published: December 2017

The ventilatory (anaerobic) threshold for short-term exercise was defined as the work rate or O2 uptake (VO2) immediately below the work rate at which ventilation increased disproportionately relative to work rate or VO2, and the ventilatory threshold for long-term exercise as the work rate or VO2 immediately below the work rate at which ventilation continued to increase with time rather than attain a steady state. The purpose of the present study was to investigate how both thresholds relate to each other and how they relate to other measures of physical performance capacity. The subjects were eight healthy males, 20-53 yr of age. Maximal performance capacity was estimated by measurements of maximal O2 uptake (VO2 max) and by endurance performance during a 12-min distance run. A high interrelationship was found between the two thresholds (r = 0.84), and each threshold expressed in VO2 (ml X min-1 X kg-1) correlated highly with VO2 max (r = 0.87 and r = 0.75, for short-term and long-term exercise, respectively). When the two thresholds were expressed as a percentage of VO2 max, neither threshold showed a significant relationship with VO2 max. Endurance performance was significantly correlated with both the ventilatory threshold for short-term and long-term exercise (r = 0.73 and 0.82, respectively). A stepwise multiple regression analysis indicated that the distance run in 12 min was best predicted by VO2 max (R2 = 0.66) or the ventilatory threshold for long-term exercise (R2 = 0.63). It is concluded that the ventilatory threshold for long-term exercise is a more specific measure to explain running performance than is the threshold during graded exercise.
Critical O2 transport values at lowered body temperatures in rats
Authors: Cain S. M. , Bradley W. E.
Published: December 2017

Whole-body O2 uptake (VO2) in rats was reported not to increase when total O2 transport (TOT = cardiac output X arterial O2 concentration) was increased above normal ranges when body temperature was kept at 38 degrees C (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 53: 660-664, 1982). Similar experiments were performed to see if hypothermic rats at 34 degrees C would increase VO2 with an increased TOT in an effort to generate heat. Anesthetized rats were ventilated with 9 or 12% O2 (hypoxia), room air (normoxia), and O2 (hyperoxia) to vary TOT from 52.6 to 6.6 ml X kg-1 X min-1. VO2 was measured in a closed-circuit, double servospirometer system. Although VO2 was significantly lower at 34 degrees C than the values previously found at 38 degrees C with normoxia and hyperoxia, there was no increase with increasing values of TOT. In spite of a lower plateau value of VO2 at 34 degrees C, the critical value of TOT below which VO2 could not be maintained was nearly the same as at 38 degrees C (22 ml X kg-1 X min-1). The reason for this was that O2 was less completely extracted as TOT was lowered below the critical value in the hypothermic animal. Some of the difficulty in extracting O2 at the tissues was probably due to the decrease in P50 (PO2 at 50% saturation) that occurs with decreased body temperature.