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Inhibition of nNOS expression in the macula densa by COX-2-derived prostaglandin E2
- Source :
- American Journal of Physiology - Renal Physiology; July 2004, Vol. 287 Issue: 1 pF152-F159, 8p
- Publication Year :
- 2004
-
Abstract
- It is well established that cyclooxygenase-2 (COX-2) and the neuronal form of nitric oxide synthase (nNOS) are coexpressed in macula densa cells and that the expression of both enzymes is stimulated in a number of high-renin states. To further explore the role of nNOS and COX-2 in renin secretion, we determined plasma renin activity in mice deficient in nNOS or COX-2. Plasma renin activity was significantly reduced in nNOS −/− mice on a mixed genetic background and in COX-2 −/− mice on either BALB/c or C57/BL6 congenic backgrounds. In additional studies, we accumulated evidence to show an inhibitory influence of PGE2on nNOS expression. In a cultured macula densa cell line, PGE2significantly reduced nNOS mRNA expression, as quantified by real-time RT-PCR. In COX-2 −/− mice, nNOS mRNA expression in the kidney, determined by real-time RT-PCR, was upregulated throughout the postnatal periods, ranging from postnatal day(PND) 3to PND 60. The induction of nNOS protein expression and NOS activity in COX-2 −/− mice was localized to macula densa cells using immunohistochemistry and NADPH-diaphorase staining methods, respectively. Therefore, these findings reveal that the absence of either COX-2 or nNOS is associated with suppressed renin secretion. Furthermore, the inhibitory effect of PGE2on nNOS mRNA expression indicates a novel interaction between NO and prostaglandin-mediated pathways of renin regulation.
Details
- Language :
- English
- ISSN :
- 1931857x and 15221466
- Volume :
- 287
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- American Journal of Physiology - Renal Physiology
- Publication Type :
- Periodical
- Accession number :
- ejs46331855
- Full Text :
- https://doi.org/10.1152/ajprenal.00287.2003