| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Journal of the American Society of Nephrology | ||||
| Publisher: | AMER SOC NEPHROLOGY | ||||
| Place of Publication: | WASHINGTON | ||||
| Volume: | 16 | ||||
| Number of Issue or Book Chapter: | 8 | ||||
| Page Range: | pp. 2354-2362 | ||||
| Date: | 2005 | ||||
| Institutions: | Biology, Preclinical Medicine > Institut für Physiologie | ||||
| Identification Number: |
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| Keywords: | THICK ASCENDING LIMB; NEPHROGENIC DIABETES-INSIPIDUS; RAT-KIDNEY; CYCLOOXYGENASE-2 EXPRESSION; RENIN EXPRESSION; MESSENGER-RNA; MICE LACKING; MACULA DENSA; RENOVASCULAR HYPERTENSION; ANGIOTENSIN-II; | ||||
| Dewey Decimal Classification: | 500 Science > 570 Life sciences | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 70574 |
Web of ScienceAbstract
Increased formation of prostaglandin E-2 (PGE(2)) is a key part of hyperprostaglandin E syndrome/antenatal Bartter syndrome (HPS/aBS), a renal disease characterized by NaCl wasting, water loss, and hyperreninism. Inhibition of PGE(2) formation by cyclo-oxygenase inhibitors significantly lowers patient mortality and morbidity. However, the pathogenic role of PGE(2) in HPS/aBS awaits clarification. ...
Abstract
Increased formation of prostaglandin E-2 (PGE(2)) is a key part of hyperprostaglandin E syndrome/antenatal Bartter syndrome (HPS/aBS), a renal disease characterized by NaCl wasting, water loss, and hyperreninism. Inhibition of PGE(2) formation by cyclo-oxygenase inhibitors significantly lowers patient mortality and morbidity. However, the pathogenic role of PGE(2) in HPS/aBS awaits clarification. Chronic blockade of the Na-K-2Cl co-transporter NKCC2 by diuretics causes symptoms similar to HPS/aBS and provides a useful animal model. In wild-type (WT) mice and in mice lacking distinct PGE2 receptors (EP1(-/-), EP2(-/-), EP3(-/-), and EP4(-/-)), the effect of chronic furosemide administration (7 d) on urine output, sodium and potassium excretion, and renin secretion was determined. Furthermore, furosemide-induced diuresis and renin activity were analyzed in mice with defective PGI(2) receptors (IP-/-). In all animals studied, furosemide stimulated a rise in diuresis and electrolyte excretion. However, this effect was blunted in EP1(-/-), EP3(-/-), and EP4(-/-) mice. Compared with WT mice, no difference was observed in EP2(-/-) and IP-/- mice. The furosemide-induced increase in plasma renin concentration was significantly decreased in EP4(-/-) mice and to a lesser degree also in IP-/- mice. Pharmacologic inhibition of EN receptors in furosemide-treated WT mice with the specific antagonist ONO-AE3-208 mimicked the changes in renin mRNA expression, plasma renin concentration, diuresis, and sodium excretion seen in EP4(-/-) mice. The GFR in EP4(-/-) mice was not changed compared with that in WT mice, which indicated that blunted diuresis and salt loss seen in EP4(-/-) mice were not a consequence of lower GFR. In summary, these findings demonstrate that the EN receptor mediates PGE(2)-induced renin secretion and that EP1, EP3, and EN receptors all contribute to enhanced PGE(2)-mediated salt and water excretion in the HPS/aBS model.
Metadata last modified: 19 Dec 2024 14:59
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