Hoecherl, Klaus and Kees, Frieder and Kraemer, Bernhard K. and Kurtz, Armin (2004) Cyclosporine A attenuates the natriuretic action of loop diuretics by inhibition of renal COX-2 expression. KIDNEY INTERNATIONAL, 65 (6). pp. 2071-2080. ISSN 0085-2538, 1523-1755
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Background. It is known that inhibition of cyclooxygenase (COX) impairs the renal actions of loop diuretics. Recently, we found that cyclosporine A (CsA) inhibits renal COX-2 expression. Therefore, we examined the interferences of CsA with the renal actions of loop diuretics. Method. We investigated the renal effects of furosemide administration (12 mg/day subcutaneously) in male Sprague-Dawley rats receiving in addition vehicle, CsA (15 mg/kg x day), rofecoxib (10 mg/kg x day), or a combination of both. Results. CsA, rofecoxib, and their combination lowered the furosemide-induced increase of prostaglandin E-2 (PGE(2)) and of 6-keto prostaglandin F-1alpha (6-keto PGF(1alpha)) excretion by 55% and by 70%. They also lowered furosemide stimulated renal excretion of sodium and water by about 65% and 60%. Basal as well as furosemide-induced stimulation of plasma renin activity (PRA) and of renal renin mRNA was further enhanced by CsA. In contrast, rofecoxib attenuated the furosemide-induced rise of PRA and of renin mRNA, both in the absence and in the presence of CsA. In addition, the increase in plasma 6-keto PGF(1alpha) levels by furosemide was further enhanced by CsA and was attenuated by rofecoxib. Conclusion. Taken together, our data suggest that CsA acts as an antinatriuretic, likely by the inhibition of COX-2-mediated renal prostanoid formation. Since the furosemide-induced stimulation of the renin system is not attenuated by CsA but by COX-2 inhibition, we speculate that extrarenal COX-2-derived prostanoids may be involved in the stimulation of the renin system by CsA and by loop diuretics.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYNDROME/ANTENATAL BARTTER-SYNDROME; MACULA DENSA CYCLOOXYGENASE-2; PLASMA-RENIN ACTIVITY; THICK ASCENDING LIMB; ANGIOTENSIN-II; INDUCED HYPERTENSION; SALT INTAKE; FUROSEMIDE; RATS; PROSTAGLANDIN-E2; cyclooxygenase; renin; kidney |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Jul 2021 13:54 |
| Last Modified: | 19 Jul 2021 13:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37600 |
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