Increased Expression of Renal Cyclooxygenase-2 and Neuronal Nitric Oxide Synthase in Hypertensive Cx40-Deficient Mice.

Details

Serval ID
serval:BIB_B94A14FEFFB5
Type
Article: article from journal or magazin.
Collection
Publications
Title
Increased Expression of Renal Cyclooxygenase-2 and Neuronal Nitric Oxide Synthase in Hypertensive Cx40-Deficient Mice.
Journal
Journal of Vascular Research
Author(s)
Krattinger N., Alonso F., Capponi A., Mazzolai L., Nicod P., Meda P., Haefliger J.A.
ISSN
1423-0135[electronic]
Publication state
Published
Issued date
2008
Volume
46
Number
3
Pages
188-198
Language
english
Abstract
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.
Pubmed
Web of science
Open Access
Yes
Create date
19/03/2009 12:28
Last modification date
20/08/2019 16:27
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