| Title: |
Increased Expression of Renal Cyclooxygenase-2 and Neuronal Nitric Oxide Synthase in Hypertensive Cx40-Deficient Mice |
| Authors: |
Krattinger, Nathalie; Alonso, Florian; Capponi, Alessandro; Mazzolai, Lucia; Nicod, Pascal; Meda, Paolo; Haefliger, Jacques-Antoine |
| Source: |
Journal of Vascular Research ; volume 46, issue 3, page 188-198 ; ISSN 1018-1172 1423-0135 |
| Publisher Information: |
S. Karger AG |
| Publication Year: |
2008 |
| Description: |
Cx40-deficient mice (Cx40–/–) are hypertensive due to increased renin secretion. We evaluated the renal expression of neuronal nitric oxide synthase (nNOS) and cyclooxygenases COX-1 and COX-2, three macula densa enzymes. The levels of nNOS were increased in kidneys of Cx40–/– mice, as well as in those of wild-type (WT) mice subjected to the two-kidney one-clip model of hypertension. In contrast, the levels of COX-2 expression were only increased in the hypoperfused kidney of Cx40–/– mice. Treatment with indomethacin lowered blood pressure and renin mRNA in Cx40–/– mice without affecting renin levels, indicating that changes in COX-2 do not cause the altered secretion of renin. Suppression of NOS activity by N G -nitro- L-arginine methyl ester ( L-NAME) decreased renin levels in Cx40–/– animals, indicating that NO regulates renin expression in the absence of Cx40. Treatment with candesartan normalized blood pressure in Cx40–/– mice, and decreased the levels of both COX-2 and nNOS. After a treatment combining candesartan and L-NAME, the blood pressure of Cx40–/– mice was higher than that of WT mice, showing that NO may counterbalance the vasoconstrictor effects of angiotensin II in Cx40–/– mice. These data document that renal COX-2 and nNOS are differentially regulated due to the elevation of renin-dependent blood pressure in mice lacking Cx40. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1159/000156704 |
| Availability: |
https://doi.org/10.1159/000156704; https://www.karger.com/Article/Pdf/156704 |
| Rights: |
https://www.karger.com/Services/SiteLicenses ; https://www.karger.com/Services/SiteLicenses |
| Accession Number: |
edsbas.45FAA8F8 |
| Database: |
BASE |