Increased Expression of Renal Cyclooxygenase-2 and Neuronal Nitric Oxide Synthase in Hypertensive Cx40-Deficient Mice
| Autor: | Alessandro M. Capponi, Pascal Nicod, Lucia Mazzolai, Paolo Meda, Jacques-Antoine Haefliger, Florian Alonso, Nathalie Krattinger |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Prostaglandin Antagonists Physiology Blood Pressure Nitric Oxide Synthase Type I Kidney Connexins Blood Pressure/drug effects Renin/blood Mice Prostaglandin Antagonists/pharmacology Internal medicine Renin Kidney/*enzymology Renin–angiotensin system medicine Animals RNA Messenger ddc:612 Cyclooxygenase 2/analysis/genetics/*physiology biology RNA Messenger/analysis Connexins/deficiency/*physiology Angiotensin II Mice Inbred C57BL Nitric oxide synthase Hypertension/enzymology/*etiology Candesartan medicine.anatomical_structure Endocrinology Blood pressure Cyclooxygenase 2 Hypertension Nitric Oxide Synthase Type I/analysis/genetics/*physiology biology.protein Macula densa Cyclooxygenase Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Journal of Vascular Research, Vol. 46, No 3 (2009) pp. 188-198 |
| ISSN: | 1423-0135 1018-1172 |
| DOI: | 10.1159/000156704 |
| Popis: | 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 NG-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. |
| Databáze: | OpenAIRE |
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