bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of angiotensin-(1–7)-induced inhibition of angiogenesis
Authors: Machado R. D. P. , Santos R. A. S. , Andrade S. P.
Published: December 2017

Angiotensin-(1–7) [ANG-(1–7)], an endogenous bioactive peptide constituent of the renin-angiotensin system, acts as an inhibitory growth factor in vitro and in vivo. In this study, we evaluated whether the antiangiogenic effect of ANG-(1–7) in the mouse sponge model of angiogenesis might be receptor mediated and involved in the release of nitric oxide (NO). The hemoglobin content (μg/mg wet tissue) of 7-day-old sponge implants was used as an index of the vascularization and showed that daily injections of ANG-(1–7) (20 ng) inhibited significantly the angiogenesis in the implants relative to the saline-treated group. The specific receptor antagonistd-Ala7-ANG-(1–7); A-779 prevented ANG-(1–7)-induced inhibition of angiogenesis. The antiangiogenic effect was also abolished by pretreatment with NO synthase inhibitors aminoguanidine (1 mg/ml) or N G-nitro-l-arginine methyl ester (0.3 mg/ml). Selective AT1 and AT2angiotensin-receptor antagonists and an angiotensin-converting enzyme inhibitor, in combination with ANG-(1–7) or alone, did not alter angiogenesis in the implants. These results establish that the regulation of the vascular tissue growth by ANG-(1–7) is associated with NO release by activation of an angiotensin receptor distinct from AT1 and AT2.
Rostral ventral medulla 5-HT1Areceptors selectively inhibit the somatosympathetic reflex
Authors: Miyawaki Takashi , Goodchild Ann K. , Pilowsky Paul M.
Published: December 2017

The role of the 5-hydroxytryptamine (5-HT1A) receptors in the rostral ventrolateral medulla (RVLM) on somatosympathetic, baroreceptor, and chemoreceptor reflexes was examined in anesthetized rats. Microinjection of the selective 5-HT1Aagonist 8-hydroxy-di- n-propylamino tetralin (8-OH-DPAT) decreased arterial blood pressure and splanchnic sympathetic nerve activity (SNA). Electrical stimulation of the hindlimb evoked early and late excitatory sympathetic responses. Bilateral microinjection in the RVLM of 8-OH-DPAT markedly attenuated both the early and late responses. This potent inhibition of the somatosympathetic reflex persisted even after SNA and arterial blood pressure returned to preinjection levels. Preinjection of the selective 5-HT1Aantagonist NAN-190 in the RVLM blocked the sympathoinhibitory effect of 8-OH-DPAT and attenuated the inhibitory effect on the somatosympathetic reflex. 8-OH-DPAT injected in the RVLM did not affect baroreceptor or chemoreceptor reflexes. Our findings suggest that activation of 5-HT1Areceptors in the RVLM exerts a potent, selective inhibition on the somatosympathetic reflex.
Expression of endothelial nitric oxide synthase in the postnatal developing porcine kidney
Authors: Solhaug Michael J. , Kullaprawithaya Usa , Dong Xui Q. , Dong Ke-Wen
Published: December 2017

The postnatal pattern of renal endothelial nitric oxide synthase (eNOS) is unknown. The purpose of this study was to characterize eNOS expression during maturation and compare this to neuronal NOS (nNOS). The experiments measured whole kidney eNOS mRNA expression by RT-PCR and protein content by Western blot, as well as cortical and medullary protein content in piglets at selected postnatal ages and in adult pigs. Whole kidney eNOS mRNA was compared with nNOS. Whole kidney eNOS expression decreased from the newborn to its lowest at 7 days, returning by 14 days to adult levels. This eNOS mRNA pattern contrasted with nNOS, which was highest at birth, and progressively decreased to its lowest level in the adult. At birth, cortical eNOS protein was greater than medullary, contrasting with the adult pattern of equivalent levels. In conclusion eNOS is developmentally regulated during early renal maturation and may critically participate in renal function during this period. The eNOS developmental pattern differs from nNOS, suggesting that these isoforms may have different regulatory factors and functional contributions in the postnatal kidney.
Sites and ionic mechanisms of hypoxic vasoconstriction in frog skin
Authors: Malvin Gary M. , Walker Benjimen R.
Published: December 2017

We tested the hypothesis that the cellular mechanisms mediating hypoxic vasoconstriction (HVC) in frog skin, an important vertebrate respiratory organ, are similar to those mediating HVC in the pulmonary vasculature of mammals. An accepted hypothesis in the lung is that alveolar hypoxia alters the redox potential in vascular smooth muscle cells of arterial vessels. This decreases membrane K+conductance, causing depolarization. Depolarization increases the open probability of L-type Ca2+channels, facilitating Ca2+entry into the cell, which leads to vascular smooth muscle contraction and vasoconstriction. We studied the cutaneous microcirculation of the frog ( Xenopus laevis) web by enclosing the web in a transparent chamber that was ventilated with different gas mixtures. Arteriolar and venular diameters were measured by video microscopy. Drugs were applied topically or intravascularly. A dose-dependent constriction to hypoxia occurred in arterioles but not venules, although both vessel types constricted to similar degrees to the thromboxane mimetic U-46619. The magnitude of HVC was not associated with arteriolar size. Constriction of arterioles with 4-amino pyridine, a K+-channel antagonist, was blocked by the L-type Ca2+-channel blocker nifedipine. Nifedipine also antagonized HVC and hypercapnic vasoconstriction. Bay K 8664, a drug that increases the open probability of L-type Ca2+channels, augmented HVC. These data support our hypothesis that the cellular mechanisms mediating HVC are similar in frog skin and mammalian lungs. This similarity between amphibain and mammalian tissues suggests that the mechanisms of HVC may have arisen relatively early in vertebrate evolution. In addition, because of its structural simplicity and easy accessibility, frog skin may be a useful tissue for studying this general phenomenon in vivo.
Hemodynamic, renal, and endocrine responses to acute ETA blockade at different ANG II plasma levels
Authors: Boemke Willehad , Hocher Berthold , Schleyer Nora , Krebs Martin Otto , Kaczmarczyk Gabriele
Published: December 2017

Angiotensin (ANG) II effects may be partly mediated by endothelin (ET)-1. This study analyses the hemodynamic, renal, and hormonal responses of acute ETA receptor antagonism (LU-135252) at two ANG II plasma levels in eight conscious dogs. Protocol 1 involved a 60-min baseline, followed by two doses of ANG II for 60 min each (4 and 20 ng · kg−1 · min−1), termed ANG II 4 (slightly increased) and ANG II 20 (pathophysiologically increased ANG II plasma concentration). Protocol 2 was the same as protocol 1 but included 15 mg/kg iv LU-135252 after the baseline period. Protocol 3 was a 3-h time control. ANG II without LU-135252 did not increase plasma big ET-1 and ET-1, whereas LU-135252 increased ET-1 transiently after injection. This transient ET-1 increase was not reflected in urinary ET-1 excretion. The ANG II induced decreases in sodium, water, and potassium excretion, glomerular filtration rate, and fractional sodium excretion were not different with and without LU-135252. Mean arterial pressure increased during ANG II and was not lower with LU-135252 (−6 mmHg, not significant). Most importantly, during ANG II 20 LU-135252 prevented the decrease in cardiac output. Simultaneously, systemic vascular resistance increased 40% less, pulmonary vascular resistance was maintained at baseline levels, and central venous and wedge pressure were lower. Because ANG II stimulated endothelin de novo synthesis should just have started after 2 h of ANG II infusion, there must be mechanisms other than blocking the coupling of de novo synthesized endothelins to the ETA receptors to explain the effects of acute ETA receptor inhibition in our setting.
Troglitazone stimulates pancreatic growth in congenitally CCK-A receptor-deficient OLETF rats
Authors: Jia Dong Mei , Fukumitsu Ken-Ichiro , Tabaru Akinari , Akiyama Toshiharu , Otsuki Makoto
Published: December 2017

We examined the effect of troglitazone treatment on pancreatic growth in the CCK-A receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rat, an animal model for type 2 diabetes mellitus. A troglitazone-rich diet (0.2%) was given from 12 to 28 wk of age or from 12 or 28 wk of age to 72 wk of age. Fasting serum glucose concentrations in control OLETF rats increased progressively with age, which was almost completely prevented by troglitazone treatment. Insulin levels in serum and pancreatic content in the control rat markedly increased at 28 wk of age but significantly decreased at 72 wk of age compared with those at 12 wk of age, whereas those in troglitazone-treated rats were nearly the same at all ages and were similar to those in control rats at 12 wk of age. Pancreatic wet weight in control rats decreased with age irrespective of whether they were hyperinsulinemic (28 wk old) or hypoinsulinemic (72 wk old). Troglitazone treatment significantly increased pancreatic wet weight and protein, DNA, and enzyme contents compared with those in the control rats. Moreover, troglitazone treatment completely prevented or reversed histological alterations such as fibrosis, fatty replacement, and inflammatory cell infiltration. Our results indicate that troglitazone stimulates pancreatic growth in the congenitally CCK-A receptor-deficient OLETF rat not only by reducing insulin resistance and potentiating insulin action but also by suppressing inflammatory changes in the pancreas.
Effect of suprachiasmatic nucleus lesion on circadian dentin increment in rats
Authors: Ohtsuka-Isoya Mie , Hayashi Haruhide , Shinoda Hisashi
Published: December 2017

Mammalian dentin universally shows circadian increments. However, little is known about the mechanism of this phenomenon. The purpose of the present study was to investigate the role of the suprachiasmatic nucleus (SCN) in the generation of circadian rhythm in dentin increment. Rats underwent lesion of the SCN by electrodes and were maintained under constant light to examine whether the circadian increment free runs. The rats were injected with nitrilotriacetato lead to chronologically label the growing dentin. Two weeks after the operation, maxillary incisors and the locations of lesions in the brain were examined histologically. A harmonic (Fourier) analysis was performed to examine the densitometric pattern of the dentin increments to determine their periodicity. In rats with a completely lesioned SCN, ultradian increments, but no circadian increments, were observed in the dentin. Alternatively, in rats with an intact or only partially lesioned SCN, circadian increments persisted or were only temporarily disturbed. These results suggest that the SCN plays an important role in the generation of the circadian dentin increment in rats.
Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition-reflex pathway in the rat
Authors: Kakizaki Hidehiro , Yoshiyama Mitsuharu , Koyanagi Tomohiko , De Groat William C.
Published: December 2017

5-Hydroxytryptamine (5-HT) receptors in the central nervous system have been implicated in the control of micturition. The present study was undertaken to evaluate the effects of a selective 5-HT1A-receptor antagonist { N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY100635)} on the micturition-reflex pathway in urethane-anesthetized female Wistar rats. Rhythmic isovolumetric bladder contractions evoked by bladder distension were abolished by 0.3- to 3-mg/kg iv or 30- to 100-μg intrathecal (it) administration of WAY100635 in a dose-dependent manner for periods of 3–15 min. Intrathecal injection of WAY100635 was effective only if injected at the L6-S1 spinal cord level, but not at the thoracic or cervical cord levels. WAY100635 (30–100 μg it) significantly reduced the amplitude of bladder contractions evoked by electrical stimulation of the pontine micturition center. However, the field potentials in the rostral pons evoked by electrical stimulation of pelvic nerve were not affected by intrathecal or intravenous injection of WAY100635. These results suggest that 5-HT1A receptors at the L6-S1 level of the spinal cord have an important role in the tonic control of the descending limb of the micturition-reflex pathway in the rat.
Low levels of KATPchannel activation decrease excitability and contractility of urinary bladder
Authors: Petkov Georgi V. , Heppner Thomas J. , Bonev Adrian D. , Herrera Gerald M. , Nelson Mark T.
Published: December 2017

Activation of ATP-sensitive potassium (KATP) channels can regulate smooth muscle function through membrane potential hyperpolarization. A critical issue in understanding the role of KATPchannels is the relationship between channel activation and the effect on tissue function. Here, we explored this relationship in urinary bladder smooth muscle (UBSM) from the detrusor by activating KATPchannels with the synthetic compounds N-(4-benzoylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide (ZD-6169) and levcromakalim. The effects of ZD-6169 and levcromakalim on KATPchannel currents in isolated UBSM cells, on action potentials, and on related phasic contractions of isolated UBSM strips were examined. ZD-6169 and levcromakalim at 1.02 and 2.63 μM, respectively, caused half-maximal activation (K1/2) of KATPcurrents in single UBSM cells (see Heppner TJ, Bonev A, Li JH, Kau ST, and Nelson MT. Pharmacology 53: 170–179, 1996). In contrast, much lower concentrations (K1/2= 47 nM for ZD-6169 and K1/2= 38 nM for levcromakalim) caused inhibition of action potentials and phasic contractions of UBSM. The results suggest that activation of <1% of KATPchannels is sufficient to inhibit significantly action potentials and the related phasic contractions.
Staphylococcal enterotoxin B induces fever, brain c-Fos expression, and serum corticosterone in rats
Authors: Goehler Lisa E. , Gaykema Ron P. A. , Hansen Michael K. , Kleiner Jayme L. , Maier Steven F. , Watkins Linda R.
Published: December 2017

The paraventricular nucleus of the hypothalamus (PVH) occupies a pivotal point within the network of brain nuclei coordinating critical host-defense responses. In mice, T cell-dependent immune stimuli, including the bacterial superantigen staphylococcal enterotoxin B (SEB), can activate the PVH. To determine whether T cell-dependent immune stimuli activate the PVH in rats, we assessed plasma corticosterone (Cort) levels, fever responses, and c-Fos expression in the PVH in animals treated with intraperitoneal injections of SEB. In animals with previously implanted abdominal thermisters, intraperitoneal injection of 1 mg/kg SEB resulted in a significant rise in body temperature, with a latency of 3.5–4 h. In separate animals, intraperitoneal injection of 1 mg/kg SEB resulted in a significant elevation of plasma Cort and induced c-Fos expression in parvocellular neurons within the PVH. These results support the idea that T cell-dependent immune stimuli activate brain pathways mediating host-defense responses such as fever and neuroendocrine changes.
Activation of histamine H3 receptors inhibits renal noradrenergic neurotransmission in anesthetized dogs
Authors: Yamasaki Tomoyuki , Tamai Isao , Matsumura Yasuo
Published: December 2017

To investigate the possible involvement of histamine H3 receptors in renal noradrenergic neurotransmission, effects of (R)alpha-methylhistamine (R-HA), a selective H3-receptor agonist, and thioperamide (Thiop), a selective H3-receptor antagonist, on renal nerve stimulation (RNS)-induced changes in renal function and norepinephrine (NE) overflow in anesthetized dogs were examined. RNS (0.5–2.0 Hz) produced significant decreases in urine flow and urinary sodium excretion and increases in NE overflow rate (NEOR), without affecting renal hemodynamics. When R-HA (1 μg · kg−1 · min−1) was infused intravenously, mean arterial pressure and heart rate were significantly decreased, and there was a tendency to reduce basal values of urine flow and urinary sodium excretion. During R-HA infusion, RNS-induced antidiuretic action and increases in NEOR were markedly attenuated. Thiop infusion (5 μg · kg−1 · min−1) did not affect basal hemodynamic and excretory parameters. Thiop infusion caused RNS-induced antidiuretic action and increases in NEOR similar to the basal condition. When R-HA was administered concomitantly with Thiop infusion, R-HA failed to attenuate the RNS-induced antidiuretic action and increases in NEOR. However, in the presence of pyrilamine (a selective H1-receptor antagonist) or cimetidine (a selective H2-receptor antagonist) infusion, R-HA attenuated the RNS-induced actions, similarly to the case without these antagonists. Thus functional histamine H3 receptors, possibly located on renal noradrenergic nerve endings, may play the role of inhibitory modulators of renal noradrenergic neurotransmission.
Fever and behavioral thermoregulation in young and old rats
Authors: Florez-Duquet Maria , Peloso Elizabeth , Satinoff Evelyn
Published: December 2017

At standard laboratory ambient temperatures (Ta) of 20–24°C, peripheral injections of lipopolysaccharide (LPS) reliably produce fever in young rats. In contrast, old rats may show a blunted fever, no fever, or even hypothermia after LPS. In the present study we hypothesized that old rats might use behavioral thermoregulation to help them develop a fever. Young and old rats were implanted with temperature transmitters. At least 1 wk postoperatively they were placed in a thermally graded alleyway (Ta10–40°C). On the third and sixth day they were taken out of the gradient, placed at an Taof 23°C, injected intraperitoneally with LPS or saline, and left at 23°C for 3 h. At the end of that time, all young rats had become febrile, whereas the old rats had not. When the rats were replaced in the thermal gradient, the young animals continued to develop a fever that was similar to fever in young rats left at 23°C. The old animals chose significantly warmer positions in the thermal gradient than did the young animals and only then became febrile. Although there was a tendency for the young rats to prefer higher Taafter LPS than after saline, these differences were not significant. However, the differences in the old rats were significant. These results suggest that the LPS had increased the thermal set point in the old rats, but they could develop febrile responses only at the warm Tathey selected.
Increased muscle ubiquitin mRNA levels in gastric cancer patients
Authors: Bossola Maurizio , Muscaritoli Maurizio , Costelli Paola , Bellantone Rocco , Pacelli Fabio , Busquets Silvia , Argilès Josef , Lopez-Soriano Francisco J. , Civello Ignazio M. , Baccino Francesco M. , Fanelli Filippo Rossi , Doglietto Giovan Battista
Published: December 2017

The intramuscular ATP-dependent ubiquitin (Ub)-proteasome proteolytic system is hyperactivated in experimental cancer cachexia. The present study aimed at verifying whether the expression of the muscle Ub mRNA is altered in patients with cancer. Total muscle RNA was extracted using the guanidinium isothiocyanate/phenol/chloroform method from rectus abdominis biopsies obtained intraoperatively from 20 gastric cancer (GC) patients and 10 subjects with benign abdominal diseases (CON) undergoing surgery. Ub mRNA levels were measured by northern blot analysis. Serum soluble tumor necrosis factor receptor (sTNFR) was measured by ELISA. Ub mRNA levels (arbitrary units, means ± SD) were 2,345 ± 195 in GC and 1,162 ± 132 in CON ( P = 0.0005). Ub mRNA levels directly correlated with disease stage ( r = 0.608, P = 0.005), being 1,945 ± 786 in stages I and II, 2,480 ± 650 in stage III, and 3,799 ± 66 in stage IV. Ub mRNA and sTNFR did not correlate with age and nutritional parameters. This study confirms experimental data indicating an overexpression of muscle Ub mRNA in cancer cachexia. Lack of correlation with nutritional status suggests that Ub activation in human cancer is an early feature that precedes any clinical sign of cachexia.
Long-term control of renal blood flow: what is the role of the renal nerves?
Authors: Barrett Carolyn J. , Navakatikyan Michael A. , Malpas Simon C.
Published: December 2017

We have developed a system for long-term continuous monitoring of cardiovascular parameters in rabbits living in their home cage to assess what role renal sympathetic nerve activity (RSNA) has in regulating renal blood flow (RBF) in daily life. Blood pressure, heart rate, locomotor activity, RSNA, and RBF were recorded continuously for 4 wk. Beginning 4–5 days after surgery a circadian rhythm, dependent on feeding time, was observed. When averaged over all days RBF to the innervated and denervated kidneys was not significantly different. However, control of RBF around these mean levels was dependent on the presence of the renal sympathetic nerves. In particular we observed episodic elevations in heart rate and other parameters associated with activity. In the denervated kidney, during these episodic elevations, the increase in renal resistance was closely related to the increase in arterial pressure. In the innervated kidney the renal resistance response was significantly more variable, indicating an interaction of the sympathetic nervous system. These results indicate that whereas overall levels of RSNA do not set the mean level of RBF the renal vasculature is sensitive to episodic increases in sympathetic nerve activity.
Splenic denervation worsens lipopolysaccharide-induced hypotension, hemoconcentration, and hypovolemia
Authors: Andrew Peter S. , Kaufman Susan
Published: December 2017

During lipopolysaccharide (LPS)-induced endotoxemia, increased intrasplenic fluid efflux contributes to a reduction in plasma volume. We hypothesized that splenic sympathetic nerve activity (SSNA), which increases during endotoxemia, limits intrasplenic fluid efflux. We reasoned that splenic denervation would exaggerate LPS-induced intrasplenic fluid efflux and worsen the hypotension, hemoconcentration, and hypovolemia. A nonlethal dose of LPS (150 μg · kg−1 · h−1 for 18 h) was infused into conscious male rats bearing transit time flow probes on the splenic artery and vein. Fluid efflux was estimated from the difference in splenic arterial inflow and venous outflow (A-V). LPS significantly increased the (A-V) flow differential (fluid efflux) in intact rats (saline −0.01 ± 0.02 ml/min, n = 8 vs. LPS +0.21 ± 0.06 ml/min, n = 8); this was exaggerated in splenic denervated rats (saline −0.03 ± 0.01 ml/min, n = 7 vs. LPS +0.41 ± 0.08 ml/min, n = 8). Splenic denervation also exacerbated the LPS-induced hypotension, hemoconcentration, and hypovolemia (peak fall in mean arterial pressure: denervated 19 ± 3 mmHg, n = 10 vs. intact 12 ± 1 mmHg, n= 8; peak rise in hematocrit: denervated 6.7 ± 0.3%, n = 8 vs. intact 5.0 ± 0.3%, n = 8; decrease in plasma volume at 90-min post-LPS infusion: denervated 1.08 ± 0.15 ml/100 g body wt, n = 7 vs. intact 0.54 ± 0.08 ml/100 g body wt, n = 8). The exaggerated LPS-induced hypovolemia associated with splenic denervation was mirrored in the rise in plasma renin activity (90 min post-LPS: denervated 11.5 ± 0.8 ng · ml−1 · h−1, n = 9 vs. intact 6.6 ± 0.7 ng · ml−1 · h−1, n = 8). These results are consistent with our proposal that SSNA normally limits LPS-induced intrasplenic fluid efflux.
Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics
Authors: Mollanji R. , Bozanovic-Sosic R. , Silver I. , Li B. , Kim C. , Midha R. , Johnston M.
Published: December 2017

Tracer studies indicate that cerebrospinal fluid (CSF) transport can occur through the cribriform plate into the nasal submucosa, where it is absorbed by cervical lymphatics. We tested the hypothesis that sealing the cribriform plate extracranially would impair the ability of the CSF pressure-regulating systems to compensate for volume infusions. Sheep were challenged with constant flow or constant pressure infusions of artificial CSF into the CSF compartment before and after the nasal mucosal side of the cribriform plate was sealed. With both infusion protocols, the intracranial pressure (ICP) vs. flow rate relationships were shifted significantly to the left when the cribriform plate was blocked. This indicated that obstruction of the cribriform plate reduced CSF clearance. Sham surgical procedures had no significant effects. Estimates of the proportional flow through cribriform and noncribriform routes suggested that cranial CSF absorption occurred primarily through the cribriform plate at low ICPs. Additional drainage sites (arachnoid villi or other lymphatic pathways) appeared to be recruited only when intracranial pressures were elevated. These data challenge the conventional view that CSF is absorbed principally via arachnoid villi and provide further support for the existence of several anatomically distinct cranial CSF transport pathways.
Pancreatic islet blood flow in conscious rats during hyperglycemia and hypoglycemia
Authors: Iwase M. , Tashiro K. , Uchizono Y. , Goto D. , Yoshinari M.
Published: December 2017

Anesthesia affects general hemodynamics and regulation of organ perfusion. We used colored microspheres to measure pancreatic islet blood flow in conscious rats at two time points, during either hyperglycemia or hypoglycemia. This method, using black and green microspheres, was validated by comparison with previous microsphere experiments and by lack of effect of a nonmetabolizable glucose analog, 3- O-methylglucose, on islet perfusion. Basal and glucose-stimulated islet blood flow levels were similar in pentobarbital sodium-anesthetized and conscious rats. However, the basal distribution of pancreatic blood flow was altered by anesthesia (fractional islet blood flow 5.8 ± 0.4% in conscious rats, 7.9 ± 0.8% in pentobarbital-anesthetized rats, P < 0.05). Insulin-induced hypoglycemia significantly increased whole pancreatic blood flow in conscious rats, whereas islet blood flow remained unchanged and fractional islet blood flow was decreased (5.8 ± 0.5% in the basal state, 4.2 ± 0.4% during hypoglycemia, P < 0.001). Methylatropine pretreatment significantly increased islet blood flow during hypoglycemia by 181%. This result suggests that prevention of hypoglycemia-induced increase in islet perfusion may be mediated, at least in part, by a cholinergic, vagal muscarinic mechanism.
In vitro and in vivo evaluation of proximal tubular acidification in aging rats
Authors: Mac Laughlin Myriam , Damasco María Cristina , Igarreta Pilar , Amorena Carlos
Published: December 2017

The normal aging process is accompanied by a progressive deterioration of renal function. We studied the kinetics of proximal tubular acidification of young (3 mo) and aging (22 mo) rats using in vivo and in vitro techniques. Blood acid-base parameters were similar in both groups. The maximum velocity of the Na+/H+exchange (NHE) in brush-border membrane vesicles (BBMV) showed a 72% decrease in aging compared with young rats, whereas the Michaelis constant remained unchanged. The NHE3 isoform of the Na+/H+exchanger was detected in BBMV by Western blot in both groups, and a decrease of 90% in the abundance was observed in aging rats. Micropuncture experiments with simultaneous luminal and peritubular perfusion with phosphate Ringer and continuous measurement of intratubular pH showed an acidification rate constant 34% smaller in aging compared with young rats. Proton flux was 48% lower in aging than in young rats. The present results suggest that proximal tubular acidification is impaired with aging.
D1dopamine receptor regulation of NHE3 during development in spontaneously hypertensive rats
Authors: Li Xiao Xi , Xu Jing , Zheng Shaopeng , Albrecht Frederick E. , Robillard Jean E. , Eisner Gilbert M. , Jose Pedro A.
Published: December 2017

To determine if the defective interactions among D1-like receptors, G proteins, and Na+/H+exchanger 3 (NHE3) are consequences of hypertension, we studied these interactions in rats, before (2–3 wk) and after (12 wk) the establishment of hypertension. To eliminate the confounding influence of second messenger action on D1receptor-NHE3 interaction, studies were performed in renal brush-border membranes (BBM) devoid of cytoplasmic second messengers. NHE3 activity increased with age in Wistar-Kyoto (WKY) rats (3 wk = 1.48 ± 0.39, n = 13; 12 wk = 2.83 ± 0.15, n = 16, P < 0.05) but not in spontaneously hypertensive rats (SHRs; 3 wk = 2.52 ± 0.37, n = 11; 12 wk = 2.81 ± 0.20, n = 16). D1receptor protein tended to decrease, whereas NHE3 protein tended to increase with age in both WKY and SHRs. However, the inhibitory effect of a D1-like agonist, SKF-81297, on NHE3 activity increased with age in WKY rats (3 wk = −40.7 ± 5.3%, n = 10, 12 wk = −58.7 ± 4.6%, n = 12, P < 0.05) but not in SHRs (3 wk = −27.6 ± 5.9%, n = 11, 12 wk = −25.1 ± 3.2%, n = 11). The decreased inhibitory effect of another D1-like agonist, fenoldopam, on NHE3 activity in SHRs was not caused by increased activity and binding of Gβγ to NHE3 as has been reported in young WKY rats. Gsα mediates, in part, the inhibitory effect of D1-like agonists on NHE3 activity. In WKY rats, fenoldopam increased Gsα/NHE3 binding to the same extent in 2-wk-old (1.5-fold, n = 4) and adult (1.5-fold, n = 4) rats. In contrast, in SHRs, fenoldopam decreased the amount of Gsα bound to NHE3 in 2-wk-old SHRs and had no effect in 4-wk-old and adult SHRs. These studies indicate that the decreased inhibitory effect of D1-like agonists on NHE3 activity in SHRs (compared with WKY rats) precedes the development of hypertension. This may be caused, in part, by a decreased interaction between Gsα and NHE3 in BBM secondary to impaired D1-like receptor function.
Inherent capacity for lipogenesis or dietary fat retention is not increased in obesity-prone rats
Authors: Commerford S. Renee , Pagliassotti Michael J. , Melby Christopher L. , Wei Yuren , Hill James O.
Published: December 2017

Obesity results from positive energy balance and, perhaps, abnormalities in lipid and glycogen metabolism. The purpose of this study was to determine whether differences in lipogenesis, retention of dietary fat, and/or glycogenesis influenced susceptibility to dietary obesity. After 1 wk of free access to a high-fat diet (HFD; 45% fat by energy) rats were separated on the basis of 1 wk body weight gain into obesity-prone (OP; ≥48 g) or obesity-resistant groups (OR; ≤40 g). Rats were either studied at this time (OR1, OP1) or continued on the HFD for an additional 4 wk (OR5, OP5). Weight gain and energy intake were greater ( P ≤ 0.05) in OP vs. OR at both 1 (53 ± 2 vs. 34 ± 1 g; 892 ± 27 vs. 755 ± 14 kcal) and 5 (208 ± 7 vs. 170 ± 7 g; 4,484 ± 82 vs. 4,008 ± 72 kcal) wk, respectively. Rats were injected with3H2O and were either provided free access to an HFD meal containing labeled fatty acids (fed; n = 10 or 11/group) or were fasted ( n = 10/group) overnight. The amount of food or14C tracer eaten overnight was equivalent between OP and OR rats. In liver, the fraction of3H retained in glycogen or lipid was not significantly different between OR and OP groups. Retention of dietary fat in the liver was not increased in OP rats. In adipose tissue, retention of3H was ∼49% greater ( P ≤ 0.05) in OP1 vs. OR1 and ∼30% greater in OP5 vs. OR5, but retention of dietary fat was not elevated in OP vs. OR. At the same time, fat pad weight (sum of epididymal, retroperitoneal, mesenteric) was 49% greater in OP1 rats vs. OR1 rats and 65% greater in OP5 vs. OR5 rats ( P ≤ 0.05). Thus a greater capacity for lipogenesis or retention of dietary fat does not appear to be included in the OP phenotype. The characteristic increase in energy intake associated with OP rats appears to be necessary and critical to accelerated weight and fat gain.
Sympathetic nerve and cardiovascular responses to chemical activation of the midbrain defense region
Authors: Larsen Peter D. , Zhong Sheng , Gebber Gerard L. , Barman Susan M.
Published: December 2017

The changes in mean arterial pressure (MAP), renal (RBF) and femoral (FBF) blood flows, and inferior cardiac (CN) and vertebral nerve (VN) sympathetic nerve discharges (SND) produced by chemical activation (d,l-homocysteic acid) of the midbrain periaqueductal gray (PAG) were compared in baroreceptor-denervated and -innervated cats anesthetized with urethan. Defenselike cardiovascular responses in both states were similar in magnitude and consisted of increased MAP and FBF and decreased RBF; however, the nerve responses differed. In baroreceptor-denervated cats, PAG activation increased CN 10-Hz activity, decreased VN 10-Hz activity, and lengthened the CN-VN phase angle. In baroreceptor-innervated cats in which the rhythm in SND was cardiac related, PAG activation increased CN activity, but VN activity and the CN-VN phase angle were unchanged. These results demonstrate that chemical activation of PAG neurons induces differential patterns of sympathetic outflow generally consistent with accompanying defenselike cardiovascular responses. However, the mechanisms responsible for the changes in 10-Hz and cardiac-related SND appear to be different.
Glucocorticoids potentiate central actions of angiotensin to increase arterial pressure
Authors: Scheuer Deborah A. , Bechtold Andrea G.
Published: December 2017

Experiments were performed to determine if glucocorticoids potentiate central hypertensive actions of ANG II. Male Sprague-Dawley rats were treated for 3 days to 3 wk with corticosterone (Cort). Experiments were performed in conscious rats that had previously been instrumented with arterial and venous catheters and an intracerebroventricular guide cannula in a lateral ventricle. Baseline arterial pressure (AP) was greater in Cort-treated rats than in control rats (119 ± 2 vs. 107 ± 1 mmHg, P < 0.01). Microinjection of ANG II intracerebroventricularly produced a significantly larger increase in AP in Cort-treated rats than in control rats. For example, at 30 ng ANG II, AP increased by 23 ± 1 and 16 ± 2 mmHg in Cort-treated and control rats, respectively ( P < 0.01). Microinjection of an angiotensin type 1 receptor antagonist significantly decreased AP (−6 ± 2 mmHg) and heart rate (−26 ± 7 beats/min) in Cort-treated but not control rats. Increases in AP produced by intravenous administration of ANG II were not different between control and Cort-treated rats. Intravenous injections of ANG II antagonist had no significant effects on mean AP or heart rate in control or Cort-treated rats. Therefore, a sustained increase in plasma Cort augments the central pressor effects of ANG II without altering the pressor response to peripheral administration of the hormone.
Altered expression of C/EBP family members results in decreased adipogenesis with aging
Authors: Karagiannides Iordanes , Tchkonia Tamara , Dobson Deborah E. , Steppan Claire M. , Cummins Patrice , Chan Gabriel , Salvatori Keith , Hadzopoulou-Cladaras Margarita , Kirkland James L.
Published: December 2017

Fat mass, adipocyte size and metabolic responsiveness, and preadipocyte differentiation decrease between middle and old age. We show that expression of CCAAT/enhancer binding protein (C/EBP)-α, a key regulator of adipogenesis and fat cell function, declined substantially with aging in differentiating preadipocytes cultured under identical conditions from rats of various ages. Overexpression of C/EBPα in preadipocytes cultured from old rats restored capacity to differentiate into fat cells, indicating that downstream differentiation-dependent genes maintain responsiveness to regulators of adipogenesis. C/EBPα-expression also decreased with age in fat tissue from three different depots and in isolated fat cells. The overall level of C/EBPβ, which modulates C/EBPα-expression, did not change with age, but the truncated, dominant-negative C/EBPβ-liver inhibitory protein (LIP) isoform increased in cultured preadipocytes and isolated fat cells. Overexpression of C/EBPβ-LIP in preadipocytes from young rats impaired adipogenesis. C/EBPδ, which acts with full-length C/EBPβ to enhance adipogenesis, decreased with age. Thus processes intrinsic to adipose cells involving changes in C/EBP family members contribute to impaired adipogenesis and altered fat tissue function with aging. These effects are potentially reversible.
Hypoxic ventilatory depression in dogs
Authors: Morrill C. G. , Meyer J. R. , Weil J. V.
Published: December 2017

It is well known that hypoxia, acting mainly through peripheral chemoreceptors, is an important ventilatory stimulus. It is also known that under certain circumstances hypoxia can lead to ventilatory depression, perhaps through its effect on the central nervous system. This study, utilizing dogs, was carried out to determine the degree of hypoxia required to produce ventilatory depression and to study the effects of chloralose anesthesia, variations in blood carbon dioxide tension, and peripheral chemoreceptor denervation on hypoxic ventilatory depression. In the awake, intact dog, ventilatory depression did not occur until the Pao2 = 18.6 plus or minus 0.8 mmHg (SEM). This value was not significantly different from that observed in chloralose anesthetized dogs, Pao2 = 18.7 plus or minus 0.43 mmHg. Hyper- and hypocapnia had no significant effect on the Pao2 at which ventilatory depression occurred. Denervation of either aortic or carotid chemoreceptors produced a very small change in the Pao2 of ventilatory depression, increasing it from 18.6 plus or minus 0.58 to 20.8 plus or minus 0.93 mmHg. Denervation of both aortic and carotid chemoreceptors produced a further small increase (Pao2 = 21.8 plus or minus 0.76 mm Hg). In peripheral chemoreceptor-denervated animals, hypoxia produced no significant change in ventilation until the ventilatory depression point was reached. These studies indicate that in the dog hypoxic ventilatory depression occurs only during severe hypoxia and ventilatory depression occurs only during severe hypoxia and is uninfluenced by chloralose anesthesia, hyper- or hypocapnia, and only slightly affected by chemoreceptor denervation.
A respiratory valve for rapid switching between two gas mixtures
Authors: Smith C. A. , Kellogg R. H.
Published: December 2017

We have devised a respiratory valve that facilitates rapid and silent breath-to-breath switching between two gas mixtures, under remote control. It utilizes two inspiratory Loven-type valve elements, one for each gas mixture, either of which can be held closed with an electromagnet. Any type of valve element can serve as the expiratory valve. We have used a small respiratory valve with goats and a larger model for both goat and human use.
A pressure-displacement transducer for measuring brain tissue properties in vivo
Authors: Walsh Edward K. , Schettini Alfonso
Published: December 2017

A transducer system is described which measures simultaneously the pressure and displacement as the transducer is inserted into the intracranial system. The measurements are made in vivo and with the dura arachnoid membranes intact. The short-time mechanical response of the system as well as the time-dependent relaxation and creep properties can be determined.
Peripheral vascular response to norepinephrine at temperatures from 2 to 40 degrees C
Authors: Millard R. W. , Reite O. B.
Published: December 2017

The response to norepinephrine (NE) was studied in the perfused whole vascular bed and perfused arteries in situ and on helical strips of arteries and veins from the isolated duck leg. NE consistently produced vasoconstriction but the sensitivity was 3–50 times greater in the whole vascular bed than in artery segments. The drug effect was maximal at temperatures near 25 degrees C and diminished considerably at low temperatures (2–5 degrees C). Isolated helical strips of arteries and veins, when exposed to NE, showed maximal developed force at 25–30 degrees C. Tibial vessels developed only slight force at 5 degrees C while the tarsal-metatarsal and digital vessels responded even at 2 degrees C. The sensitivity to NE of both vessel types from the same region was similar. Flow in whole vascular bed perfused at constant pressure (40 cmH2O) was maximum at 30–35 degrees C. At both higher and lower temperatures flow declined and was about the same at 2 degrees C as at 40 degrees C. Our findings indicate that the vasoconstrictor effect of NE is exerted on both large and small veins and arteries; yet peripheral vessels respond more than do proximal segments at low temperatures. These findings suggest that peripheral vascular compartments may be capable of regulating regional blood flow at temperatures approaching freezing.
Energy cost of square dancing
Authors: Jette M. , Inglis H.
Published: December 2017

This experiment was concerned with determining the energy cost of two popular Western square dancing routines: the “Mish-Mash,” which is a relatively fast-moving dance with quick movements, and the “Singing” dance, which is a slower and more deliberate type of dance. The subjects were four middle-aged couples, veteran members of a local square dancing club. Sitting and standing pulmonary ventilations were determined through the use of the Tissot gasometer. Kofranyi-Michaelis respirometers were employed for the dance routine ventilations. These apparatus were fitted with a Monoghan neoprene cushion plastic mask. Gas samples were collected in polyethylene metallized bags and analyzed for O2 and CO2 content. The net energy cost for the two dances was appropriately summarized. The results indicated that for the males the net average energy cost of the “Mish-Mash,” dance was 0.085 and 0.077 kcal/min per kg for the “Singing” dance. For the females, the cost was 0.088 and 0.084 kcal/min per kg, respectively. A net average cost of these two dances yielded a caloric expenditure of 5.7 kcal/min for a 70-kg male and 5.2 kcal/min for a 60-kg female. It was indicated that during the course of a typical square dance evening, a 70-kg man would expend some 425 kcal. while a 60-kg female would burn some 390 kcal. The energy cost of the dances studied were determined to be within the permissible work load of a functional class 1 patient with diseases of the heart as determined by the American Heart Association.
Effects of atropine on natural deflation flows and P-V curves of the isolated lung lobe
Authors: Goldman E. , Puy R. J.
Published: December 2017

Static pressure-volume (P-V) curves and natural deflation flows (NDF) in isolated dog's lung lobes were obtained before and after atropine. Since elastic pressure was the driving force for the expiratory flow this preparation was devoid of the influence of compressive forces. A significant shift to the left of the P-V curve was observed after atropine. Mean increase in volume in the range from 30 to 2 cmH2O transpulmonary pressure (Ptp) was 0.6 ml/g (about 4% increase in percent of maximal lung volume MLV). NDF at the same Ptp (referred to as airway conductance) were significantly higher after atropine (mean increase 3 ml/s per g, about 0.15 l/s). Increase in lung volume after atropine was interpreted as evidence of relaxation of residual bronchomotor tone which in turn, by increasing airway diameters, may produce higher flows. When NDF were plotted against volume, differences between control and atropine were reduced. This was attributed to the observed leftward displacement of the P-V curve. The linear relationship found between NDF and volume in the range 2–8 cmH2O of Ptp (about 35–75% MLV) suggests a proportionate change in airway conductance with lung size. This could indicate that the lobes behaved homogeneously during passive deflation. This pattern was not modified by atropine.
Expiratory reserve volume and vital capacity of the lungs during immersion in water
Authors: Craig A. B. , Dvorak M.
Published: December 2017

The effects of immersion by 5-cm increments on the expiratory reserve volume of the lungs (ERV) and on the vital capacity were studied in the sitting and supine positions. These effects were compared to those produced by continuous negative-pressure breathing when the subjects were in air and were counteracted by positive pressure breathing during immersion. The depth of immersion was also related to definable anatomic landmarks. In the sitting position about one-fourth of the decrease in the ERV was accounted for by the hydrostatic pressure of the water on the abdomen and the remainder by the pressure on the thorax. Immersion to the level of the spinous process of the seventh cervical vertebra was equivalent to 28 cmH2o continuous negative pressure breathing in air. In the supine position, a comparable value was 8 cmH2o. These observations agree well with those of others if differences in the levels of immersion are accounted for.
A theory of aerosol deposition in the human respiratory tract
Authors: Taulbee D. B. , Yu C. P.
Published: December 2017

The deposition of inhaled aerosol particles in the human respiratory tract is due to the mechanisms of inertia impaction, Brownian diffusion, and gravitational settling. A theory is developed to predict the particle deposition and its distribution in human respiratory tract for any breathing condition. A convection-diffusion equation for the particle concentration with a loss term is used to describe the transport and deposition of particles. In this equation, an apparent diffusion coefficient due to the velocity dispersion in the lung is present and found to be the dominant diffusion mechanism for the cases considered here. Expressions for deposition by various mechanisms are also derived. The governing equation is solved numerically with Weibel's lung model A. The particle concentration at the mouth is calculated during washin and washout and compared favorably with experimental recordings for 0.5-mum diameter di(2-ethylhexyl) sebacate particles. The total deposition in the lung for particle size ranging from 0.05 to 5 mum is also computed for a 500-cm-3 tidal volume and 15 breaths/min. The results in general agree with recent measurements of Heyder et al. However, a particle size of minimum deposition is found to exist theoretically near 0.3 mum.
Effect of physical training on the metabolism of thyroid hormones in man
Authors: Balsam A. , Leppo L. E.
Published: December 2017

he effect of a 6-wk program of physical training (track running) on the peripheral metabolism of thyroxine (T4) and triiodothyronine (T3) was evaluated in a group of 11 men. Measurements were made of hormone turnover, urinay and fecal clearances, plasma hormone concentrations, and hormone binding by plasma proteins in all subjects before and after training, After training, metabolic clearance of T3 was increased 8.5% above the pretraining level due to an increased deiodinative clearance of this hormone. No significant change was observed in plasma T3 concentration. The absolute degradation of T3 increased 10.3% after training. In contrast, no significant change in the metabolic clearance of T4 was detected. Significantly decreased plasma concentration of total T4 after 4 and 6 wk of training was apparently not due to decreased hormone binding by plasma protein since no significant alteration in the dialyzable fraction of T4 was detected. The absolute degradation rate of T4 was decreased 8.8% after training. Possible implications of the observed differential impact of training on the degradation of T4 and T3 regarding thyroid hormone economy are discussed.