Search Results

You are looking at 41 - 50 of 317 items for :

  • User-accessible content x
Clear All
Free access

Meredith A Kelleher, Hannah K Palliser, David W Walker and Jonathan J Hirst

Therapeutics 288 679 – 684 . Kruse M Rey M Barutta J Coirini H 2009 Allopregnanolone effects on astrogliosis induced by hypoxia in organotypic cultures of striatum, hippocampus, and neocortex . Brain Research 1303 1 – 7 doi:10.1016/j

Free access

Brit H Boehmer, Sean W Limesand and Paul J Rozance

CK Lyarmush M 1993 Effect of hypoxia on insulin secretion by isolated rat and canine islets of Langerhans . Diabetes 42 12 – 21 . ( doi:10.2337/diab.42.1.12 ) 8420809 10.2337/diab.42.1.12 Doliba NM Wehrli SL Vatamaniuk MZ

Free access

A Martinez, L Saldise, MJ Ramirez, S Belzunegui, E Zudaire, MR Luquin and F Cuttitta

Adrenomedullin (AM) immunoreactivity has been found in granules of the glomus (type I) cells of the carotid bodies in rats. The identity of these cells was ascertained by colocalization of immunoreactivities for AM and tyrosine hydroxylase in their cytoplasm. Exposure of freshly isolated carotid bodies to synthetic AM resulted in a concentration- and time-dependent degranulation of glomus cells as measured by dopamine (DA) release. DA release reached a zenith 30 min after exposure to AM (94.2% over untreated controls). At this time-point, the response to AM was similar to the one elicited by 5 min of exposure to 100 mM K+. Nevertheless, injection of 1 micro l 60 nM AM/g body weight into the tail vein of the rats did not induce statistical differences in DA release from the carotid bodies. Exposure of the oxygen-sensitive cell line PC-12 to hypoxia elicited an increase in AM mRNA expression and peptide secretion into serum-free conditioned medium. Previous data have shown that elevation of AM expression under hypoxia is mediated through hypoxia-inducible factor-1, and that exposure of chromaffin cells to AM results in degranulation. All these data suggest that AM is an important autocrine regulator of carotid body function.

Free access

Fung M-L, SY Lam, X Dong, Y Chen and PS Leung

In the present study, the effects of postnatal hypoxemia on the AT1 angiotensin receptor-mediated activities in the rat carotid body were studied. Angiotensin II (Ang II) concentration-dependently increased the chemoreceptor afferent activity in the isolated carotid body. Single- or pauci-fiber recording of the sinus nerve revealed that the afferent response to Ang II was enhanced in the postnatally hypoxic carotid body. To determine whether the increased sensitivity to Ang II is mediated by changes in the functional expression of Ang II receptors in the carotid body chemoreceptors, cytosolic calcium ([Ca2+]i) was measured by spectrofluorimetry in fura-2 acetoxymethyl ester-loaded type I cells dissociated from carotid bodies. Ang II (25-100 nM) concentration-dependently increased [Ca2+]i in the type I cells. The proportion of clusters of type I cells responsive to Ang II was higher in the postnatally hypoxic group than in the normoxic control (89 vs 66%). In addition, the peak [Ca2+]i response to Ang II was enhanced 2- to 3-fold in the postnatally hypoxic group. The [Ca2+]i response to Ang II was abolished by pretreatment with losartan (1 microM), an AT1 receptor antagonist, but not by PD-123177 (1 microM), an AT(2) antagonist. Double-labeling immunohistochemistry confirmed that an enhanced immunoreactivity for AT1 receptor was co-localized to the lobules of type I cells in the hypoxic group. In addition, RT-PCR analysis of subtypes of AT1 receptors showed an up-regulation of AT1a but a down-regulation of AT1b receptors, indicating a differential regulation of the expression of AT1 receptor subtypes by postnatal hypoxia in the carotid body. These data suggest that postnatal hypoxemia is associated with an increased sensitivity of peripheral chemoreceptors in response to Ang II and an up-regulation of AT1a receptor-mediated [Ca2+]i activity of the chemoreceptors. This modulation may be important for adaptation of carotid body functions in the hypoxic ventilatory response and in electrolyte and water homeostasis during perinatal and postnatal hypoxia.

Free access

LR Green, Y Kawagoe, DJ Hill, BS Richardson and VK Han

Intermittent umbilical cord compression with resultant fetal hypoxia can have a negative impact on fetal growth and development. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are the most important regulators of fetal growth. In preterm (107-108 days of gestation) and near-term (128-131 days of gestation) ovine fetuses, we have determined the effect of intermittent umbilical cord occlusion (UCO) over a period of 4 days on the profile and expression of IGFs and IGFBPs. In experimental group animals (preterm n=7; near term n=7) UCOs were carried out by complete inflation of an occluder cuff (duration 90 s) every 30 min for 3-5 h each day, while control fetuses (preterm n=7; near term n=7) received no UCOs. Ewes were euthanized at the end of day 4, and fetal heart, lung, kidney, liver, skeletal muscle and placenta were collected. During UCOs, PO(2! ) fell (by approximately 13 mmHg), pH fell (by approximately 0.05) and PCO(2) increased (by approximately 7 mmHg), and changed to a similar extent in both preterm and near-term groups. In both preterm and near-term groups, there was no difference in fetal body or organ weight between UCO and control fetuses. No significant changes were observed in plasma IGF-I and -II concentrations or IGFBP-1, -2, -3 or -4 levels throughout the 4-day study at either gestational age. In the preterm group UCO fetuses, IGF-II mRNA (1.2-6.0 kb) levels were lower in fetal lung (33%, P<0.05), heart (54%, P<0.01) and skeletal muscle (29%, P<0.05), but there were no differences in IGF-I mRNA levels (7.3 kb); IGFBP-2 mRNA (1.5 kb) levels were lower in the right lobe of the liver (42%, P<0.05) and kidney (22%, P<0.01), but hig! her in the heart (72%, P<0.01), while IGFBP-4 (2.4 kb) levels were lower in skeletal muscle (21%, P<0.01). In the near-term group UCO fetuses, IGFBP-2 mRNA levels were greater in the placenta (39%, P<0.05). Thus, intermittent UCO as studied has a greater effect on the expression of genes encoding certain peptides of the fetal IGF system in selected tissues in preterm fetuses than that in near-term fetuses. Altered IGFBP-2 mRNA levels with reduced IGF-II mRNA levels in selected tissues may mediate changes in growth and/or differentiation that might become apparent if the length of the UCO study were extended.

Free access

Rui Song, Xiang-Qun Hu and Lubo Zhang

provide clues to understand glucocorticoids regulating DNA methylation via GR in heart development and disease. Perinatal hypoxia and glucocorticoid exposure cause fetal programming during fetal development, leading to an increased risk of adult disease

Free access

Stephen Mandang, Ursula Manuelpillai and Euan M Wallace

output remain unclear. On the basis of histological ( Brosens & Renaer 1972 ) and, more recently, molecular ( Soleymanlou et al. 2005 ) evidence of placental hypoxia in preeclampsia and on the in vivo observations in sheep that both acute

Free access

A L Pierce, M Shimizu, L Felli, P Swanson and W W Dickhoff

IGFBP-1 mRNA levels are directly increased by low amino acid levels ( Thissen et al. 1994 ) and by hypoxia ( Popovici et al. 2001 , Scharf et al. 2005 ). Both the regulation of IGFBP-1 by metabolic status and stress and its function as an

Free access

Angélica Morales, Sumiko Morimoto, Lorenza Díaz, Guillermo Robles and Vicente Díaz-Sánchez

). EG-VEGF regulation is poorly understood; nevertheless, recent studies have shown that hypoxia induces EG-VEGF expression, suggesting a role of this factor in tumorigenesis. In addition, EG-VEGF has been associated with certain EG cancers such as

Free access

Amy Hughes, Darling Rojas-Canales, Chris Drogemuller, Nicolas H Voelcker, Shane T Grey and P T H Coates

, O'Connell et al . 2013 ). Islet allotransplantation into a recipient with T1D exposes the transplanted islets to a number of apoptotic stresses, including the instant blood-mediated inflammatory reaction (IBMIR), hypoxia, inflammation, hyperglycemia