| Autor: |
Paliege A; National Institute of Diabetes and Kidney Disease, National Institutes of Health, Bethesda, MD 20892, USA., Mizel D, Medina C, Pasumarthy A, Huang YG, Bachmann S, Briggs JP, Schnermann JB, Yang T |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2004 Jul; Vol. 287 (1), pp. F152-9. Date of Electronic Publication: 2004 Mar 09. |
| DOI: |
10.1152/ajprenal.00287.2003 |
| Abstrakt: |
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 PGE(2) on nNOS expression. In a cultured macula densa cell line, PGE(2) significantly 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) 3 to 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 PGE(2) on nNOS mRNA expression indicates a novel interaction between NO and prostaglandin-mediated pathways of renin regulation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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