| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Journal of the American Society of Nephrology | ||||
| Publisher: | LIPPINCOTT WILLIAMS & WILKINS | ||||
| Place of Publication: | PHILADELPHIA | ||||
| Volume: | 13 | ||||
| Number of Issue or Book Chapter: | 5 | ||||
| Page Range: | pp. 1136-1144 | ||||
| Date: | 2002 | ||||
| Institutions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Wolf Hayo Castrop Biology, Preclinical Medicine > Institut für Anatomie | ||||
| Identification Number: |
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| Keywords: | NONSTEROIDAL ANTIINFLAMMATORY DRUG; MACULA DENSA; COLLECTING DUCT; INHIBITION; PROSTAGLANDIN-E2; TRANSPORT; KIDNEY; CELLS; RNA; | ||||
| 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: | 73014 |
Web of ScienceAbstract
It is well known that loop diuretics enhance the renal excretion of prostanoids therefore, this study aimed to characterize the influence of loop diuretics on the intrarenal expression of cyclooxygenases, which are the key enzymes for prostanoid formation. Mate Sprague-Dawley rats were infused with furosemide (12 mg/kg per d) for 6 d. and the expression of cyclooxygenase-1 and -2 (Cox-1 and ...
Abstract
It is well known that loop diuretics enhance the renal excretion of prostanoids therefore, this study aimed to characterize the influence of loop diuretics on the intrarenal expression of cyclooxygenases, which are the key enzymes for prostanoid formation. Mate Sprague-Dawley rats were infused with furosemide (12 mg/kg per d) for 6 d. and the expression of cyclooxygenase-1 and -2 (Cox-1 and Cox-2) was analyzed in the different kidney zones. Furosemide increased Cox-2 mRNA expression approximately twofold in the cortex. but it left Cox-1 mRNA expression unaltered there. In the outer medulla. furosemide changed neither Cox-1 nor Cox-2 mRNA expression. In the inner medulla, however. furosemide decreased Cox-1 and Cox-2 mRNA levels to approximately 30% and 60% of their control levels, respectively. ne downregulation of mRNA was paralleled by a decrease of Cox protein in the collecting ducts and interstitial cells. Moreover, tissue prostaglandin E-2 (PGE(2)) concentrations in the papilla were markedly decreased by furosemide to about 30% of the control level. Furosemide lowered urine osmolality from 1550 mosmol/kg to 480 mosmol/kg: therefore. further consideration was given to the influence of tonicity as a possible mediator of the effects of furosemide on the Cox expression. Water loading was therefore used to reduce the medullary tonicity by a second maneuver. Water loading led to a similar reduction in papillary Cox mRNA expression and PGE(2) content like furosemide. To investigate the influence of the osmolarity on the expression of Cox and the production of PGE(2) under defined in vitro conditions, inner medullary collecting duct cells were incubated with culture medium containing graded amounts of NaCl ranging from 200 mmol/L to 600 mmol/L, and Cox-1 and Cox-2 mRNA abundance were determined after 24 h an 48 h. Cox-1 and Cox-2 mRNA abundance changed in parallel with the osmolarity. The data suggest that loop diuretics decrease the expression of cyclooxygenases and consequently tissue PGE(2) concentrations in the kidney inner medulla. This effect could be related to the breakdown of the papillary osmotic gradient induced by loop diuretics.
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