Browsing by Author "Valdes, G"

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    Distribution of angiotensin-(1-7) and ACE2 in human placentas of normal and pathological pregnancies
    (W B SAUNDERS CO LTD, 2006) Valdes, G; Neves, LAA; Anton, L; Corthorn, J; Chacon, C; Germain, AM; Merrill, DC; Ferrario, CM; Sarao, R; Penninger, J; Brosnihan, KB
    This work was designed to study the expression of the vasodilator peptide angiotensin-(1-7) [Ang-(1-7)] and its generating enzyme (ACE2) in the uteroplacental interface. Placentas were obtained from 11 early pregnancy failures (5 miscarriages and 6 ectopic pregnancies), 15 normotensive, and 10 preeclamptic gestations. In placental villi, the main sites of immunocytochemical expression of Ang-(1-7) and ACE2 were the syncytiotrophoblast, cytotrophoblast, endothelium and vascular smooth muscle of primary and secondary villi. Syncitial Ang-(1-7) expression in samples obtained from miscarriages and ectopic pregnancies was increased compared to normal term pregnancy [2.0 (2.0-2.25 for the 25 and 75% interquartile range) vs 1.3 (1.0-1.9), p < 0.01]. In the maternal stroma, Ang-(1-7) and ACE2 were expressed in the invading and intravascular trophoblast and in decidual cells in all 3 groups. Ang-(1-7) and ACE2 staining was also found in arterial and venous endothelium and smooth muscle of the umbilical cord. The expression of Ang-(1-7) and ACE2 was similar in samples obtained from normal term or preeclamptic pregnancies, except for increased expression of ACE2 in umbilical arterial endothelium in preeclarmpsia [0.5 (0.5-0.8) vs 0.0 (0.0-0.0), p < 0.01]. The uteroplacental location of Ang-(1-7) and ACE2 in pregnancy suggests an autocrine function of Ang-(1-7) in the vasoactive regulation that characterizes placentation and established pregnancy. (c) 2005 Elsevier Ltd. All rights reserved.
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    Estrogen and luminal stimulation of rat uterine kallikrein
    (OXFORD UNIV PRESS INC, 1997) Corthorn, J; Figueroa, C; Valdes, G
    To understand the regulation of rat uterine kallikrein, we evaluated its variations in animals that had been ovariectomized and supplemented with estradiol or progesterone, in pseudopregnant animals intraluminally oil-stimulated or unstimulated, and in unilaterally pregnant animals. The content of kallikrein, determined by an RIA highly specific for rK1 (true tissue kallikrein), rose in ovariectomized rats with estradiol supplementation (0.28 +/- 0.03 to 0.44 +/- 0.05 ng/mg) and decreased with progesterone (0.13 +/- 0.02 ng/mg; n = 15; p < 0.001). Kallikrein content rose from Day 1 of pseudopregnancy (PP1) to a maximum on PP7 (0.18 +/- 0.01 to 0.39 +/- 0.04 ng/mg protein; n = 36; p < 0.001). On PP7 with unilateral oil intraluminal stimulation, the decidualized horn had higher kallikrein content than did the contralateral (0.98 +/- 0.09 vs. 0.35 +/- 0.05 ng/mg protein; n = 7; p < 0.001). Immunocytochemistry revealed that mainly rK1 is localized in the luminal and glandular epithelium, and it increased in the stimulated horn. In the unilaterally pregnant rat on Day 7, the fertile horn had a higher kallikrein content than its contralateral control (0.71 +/- 0.07 vs. 0.37 +/- 0.03 ng/mg protein, pt 0.001; n = 8), as well as a higher kininogenase activity (239 +/- 34.3 vs. 83.5 +/- 7.9 ng bradykinin(BK)/h per horn, p < 0.003; and 945 +/- 90 vs. 585 +/- 40 ng 8K/h per gram tissue, p < 0.002; n = 6). These results indicate that estrogen stimulates, whereas progesterone inhibits, kallikrein production, and that hormonal regulation is overridden by intraluminal stimulation, thus associating the enzyme with decidualization.
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    Temporospatial changes of kallikrein-like enzymes during the estrous cycle and pregnancy in the rat uterus
    (SOC STUDY REPRODUCTION, 1996) Valdes, G; Figueroa, CD; Corthorn, J
    We have recently reported the presence of uterine glandular kallikrein in the rat, its mRNA, and its increase in early gestation. This study describes its immunolocalization, by polyclonal antibodies against rat urinary kallikrein, during the estrous cycle and pregnancy, and identifies three members of the kallikrein family. During the estrous cycle, immunoreactivity, represented by an apical rim in the luminal and glandular epithelium, was greater during proestrus. On Day 5 of gestation, the reaction increased, and on Day 6 staining appeared in the apical and basal pole of some cells, On Day 7, staining was markedly increased in the glandular epithelium at the implantation site, frequently occupying the whole cytoplasm, and displaying great intensity in isolated glandular cells; the epithelium of the implantation chamber showed apical immunoreactivity, while the interimplantation zone had a few faintly stained glands. At this stage, the staining represented expression of two of the enzymes, rK1 and rK7. On Days 9 and 10, the staining disappeared, to reappear on Day 12 in the cells underlying the blood vessels of the central subplacental region. On Days 16 and 21, kallikrein staining surrounded the subendothelium of the sinusoids of the whole decidua basalis. This subplacental reaction represented expression of rK1, rK2, and rK7. This study shows important changes in the immunocytochemical expression of three uterine kallikrein-like enzymes during the reproductive cycle, associated with different hormonal milieus and with local stimulation. The localization of these enzymes is associated with areas involved in implantation, trophoblast penetration, and placental blood flow regulation.
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    Temporospatial changes of kinin B2 receptors during the estrous cycle and pregnancy in the rat uterus
    (SOC STUDY REPRODUCTION, 2001) Figueroa, CD; Chacon, C; Corthorn, J; Ehrenfeld, P; Muller Esterl, W; Valdes, G
    Tissue kallikreins are present in rat uterus during the estrous cycle in luminal and glandular epithelium, in early gestation in the implantation node, and in the last third of pregnancy surrounding the sinusoids in the decidua basalis. The pattern of kinin B2 receptor expression, through which the vasoactive effect of kallikreins is exerted, was studied by in vitro autoradiography and immunohistochemistry. The kinin B2 receptor was observed in the luminal and glandular epithelium, myometrium, endothelial cells of arteries, veins and venules, and smooth muscle cells of endometrial and myometrial arterioles. Immunoblotting of crude membranes revealed a band of 69 kDa that increased in late proestrus and estrus, concordantly with the pattern of immunostaining observed in the tissue. At Day 7 of gestation, the kinin B2 receptor was expressed (binding sites and receptor protein) in the epithelium of the implantation node and decidual cells; these latter cells showed a further increase during gestational Days 9 and 10. From Days 14 to 21, the subplacental decidua became strongly immunoreactive, and on Days 16 and 21 the placental labyrinthine endothelium was intensely stained. During this period, endothelium of arteries and veins, smooth muscular cells of small diameter arterioles, and myometrium also expressed B2 receptors. In unilaterally oil-stimulated pseudopregnancy, the decidual cells and the glandular epithelium show similar immunoreactivity to that during pregnancy. The temporospatial pattern of kinin B2 receptors, coinciding with that of kallikrein or with sites accessible to the generated kinins, further supports an autocrine-paracrine role for the kallikreinkinin system in the vasoactive changes of implantation and placental blood flow regulation.
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    Urinary kallikrein excretion in the human menstrual cycle, normal pregnancy and lactation
    (PARTHENON PUBLISHING GROUP, 1998) Valdes, G; Corthorn, J; Oyarzun, E; Berrios, C; Foradori, A; Germain, AM; Villarroel, L
    Objectives To evaluate the temporal pattern of active and total urinary kallikrein excretion during the menstrual cycle, pregnancy and lactation, and to associate changes in kallikrein excretion with those of ovarian and placental hormones.