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Increased expression of renal cyclooxygenase-2 and neuronal nitric oxide synthase in hypertensive Cx40-deficient mice

Krattinger, Nathalie
Alonso, Florian
Mazzolai, Lucia
Nicod, Pascal
Haefliger, Jacques-Antoine
Published in Journal of Vascular Research. 2009, vol. 46, no. 3, p. 188-198
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.
Keywords AnimalsBlood Pressure/drug effectsConnexins/deficiency/*physiologyCyclooxygenase 2/analysis/genetics/*physiologyHypertension/enzymology/*etiologyKidney/*enzymologyMiceMice, Inbred C57BLNitric Oxide Synthase Type I/analysis/genetics/*physiologyProstaglandin Antagonists/pharmacologyRNA, Messenger/analysisRenin/blood
PMID: 18812700
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KRATTINGER, Nathalie et al. Increased expression of renal cyclooxygenase-2 and neuronal nitric oxide synthase in hypertensive Cx40-deficient mice. In: Journal of Vascular Research, 2009, vol. 46, n° 3, p. 188-198. https://archive-ouverte.unige.ch/unige:19898

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Deposited on : 2012-04-23

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