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Renal Inhibition of Heme Oxygenase-1 Increases Blood Pressure in Angiotensin II-Dependent Hypertension
The goal of this study was to test the hypothesis that renal medullary heme oxygenase (HO) acts as a buffer against Ang-II dependent hypertension. To test this hypothesis, renal medullary HO activity was blocked using QC-13, an imidazole-dioxolane HO-1 inhibitor, or SnMP, a classical porphyrin based...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227477/ https://www.ncbi.nlm.nih.gov/pubmed/22164328 http://dx.doi.org/10.1155/2012/497213 |
Sumario: | The goal of this study was to test the hypothesis that renal medullary heme oxygenase (HO) acts as a buffer against Ang-II dependent hypertension. To test this hypothesis, renal medullary HO activity was blocked using QC-13, an imidazole-dioxolane HO-1 inhibitor, or SnMP, a classical porphyrin based HO inhibitor. HO inhibitors were infused via IRMI catheters throughout the study starting 3 days prior to implantation of an osmotic minipump which delivered Ang II or saline vehicle. MAP was increased by Ang II infusion and further increased by IRMI infusion of QC-13 or SnMP. MAP averaged 113 ± 3, 120 ± 7, 141 ± 2, 153 ± 2, and 154 ± 3 mmHg in vehicle, vehicle + IRMI QC-13, Ang II, Ang II + IRMI QC-13, and Ang II + IRMI SnMP treated mice, respectively (n = 6). Inhibition of renal medullary HO activity with QC-13 in Ang II infused mice was also associated with a significant increase in superoxide production as well as significant decreases in antioxidant enzymes catalase and MnSOD. These results demonstrate that renal inhibition of HO exacerbates Ang II dependent hypertension through a mechanism which is associated with increases in superoxide production and decreases in antioxidant enzymes. |
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