- / Background: Endothelin-1 (ET-1), a strong vasoconstrictive substance acting via
stimulation of specific receptors (ET-A and ET-B), has been implicated in the
development of renal scarring. Activation of endothelin system was observed in
experimental models of glomerular diseases and this was attributed to the toxic action
of proteinuria to the tubular epithelial cells. However, we have not enough
information about the role of endothelin system in human glomerular diseases and in
renal diseases without proteinuria like obstructive nephropathy. The aim of this study
was to examine the endothelin system in patients with primary glomerular diseases
and in experimental animals with unilateral ureteric obstruction. Patients and
Methods: Thirty-seven patients with different types of primary glomerulonephritides
and 14 controls were included in the study. Patients presented by either nephrotic
syndrome (n=25) or mild proteinuria (<1g/24h, n=12). The expression of ET-A and
ET-B receptors in the renal tissue was examined immunohistochemically. At the time
of biopsy, urinary ET-1 was determined by RIA. Experimental animals and
Methods: Twenty –day old opossum pups (n=6) underwent surgical ligation of the
left ureter. Sham operated animals, non-operated controls and normal human kidneys
were also used. Animals were sacrificed at 2 (n=2), 3 (n=1), 4 (n=1), 5(n=1) and 8
(n=1) weeks post surgery and their kidneys were examined. Sham operation was
performed at equivalent times in pups that served as control. The expression of ET-A
and ET-B receptors in the renal tissue was examined immunohistochemically.
Results: The expression of both receptors was mainly localized within tubular
epithelial cells and was significantly higher in patients with glomerulonephritides
compared to controls. The expression of ET-B receptors was higher in nephrotic
compared to non-nephrotic patients while no difference was observed in the
expression of ET-A receptors. Urinary excretion of ET-1 was increased in patients
compared to healthy subjects (579±146 ng/24h vs. 410±78 ng/24h, p<0.01) and it was
higher in nephrotic compared to non-nephrotic patients (617±167 ng/24h vs. 485±71
ng/24h, p<0.05). A significant positive correlation of the excreted ET-1 with the
degree of proteinuria (r= 0.338, p<0.05) and the extent of immunostaining for ET-B
receptors (r=0.427, p<0.05) was observed. The expression of ET-B receptors and the
excretion of ET-1 were significantly decreased in patients who present remission of
the nephrotic syndrome under immunosuppressive therapy. In tubular epithelial cells of the experimental animals there was a temporal increase in the expression of ET-A
receptors with duration of obstruction while there was no significant difference
between the expression of ET-B receptors in obstructed kidneys and controls.
Conclusions: this study provides evidence that the endothelin system is activated in
renal diseases and proteinuria seems to be related only in part to this activation.
Further investigation is needed to ascertain if the activation of endothelin system has a
causative role in the progression of renal diseases.
| Identifer | oai:union.ndltd.org:upatras.gr/oai:nemertes:10889/1213 |
| Date | 23 December 2008 |
| Creators | Δρακόπουλος, Αναστάσιος |
| Contributors | Βαράκης, Ιωάννης, Βαράκης, Ιωάννης, Βλαχογιάννης, Ιωάννης, Κούβελας, Ηλίας, Σωτηροπούλου, Γιώτα, Γούμενος, Δημήτριος, Ασημακοπούλου, Μάρθα, Λυγερού, Ζωή |
| Source Sets | University of Patras |
| Language | gr |
| Detected Language | English |
| Type | Thesis |
| Rights | 0 |
| Relation | Η ΒΥΠ διαθέτει αντίτυπο της διατριβής σε έντυπη μορφή στο βιβλιοστάσιο διδακτορικών διατριβών που βρίσκεται στο ισόγειο του κτιρίου της. |
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