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 base...
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Online Access: | http://dx.doi.org/10.1155/2012/497213 |
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doaj-b8207f96d4c44af48b99cc303824a0a42020-11-24T21:03:53ZengHindawi LimitedInternational Journal of Hypertension2090-03842090-03922012-01-01201210.1155/2012/497213497213Renal Inhibition of Heme Oxygenase-1 Increases Blood Pressure in Angiotensin II-Dependent HypertensionEva Csongradi0Megan V. Storm1David E. Stec2Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USADepartment of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USADepartment of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USAThe 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.http://dx.doi.org/10.1155/2012/497213 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eva Csongradi Megan V. Storm David E. Stec |
spellingShingle |
Eva Csongradi Megan V. Storm David E. Stec Renal Inhibition of Heme Oxygenase-1 Increases Blood Pressure in Angiotensin II-Dependent Hypertension International Journal of Hypertension |
author_facet |
Eva Csongradi Megan V. Storm David E. Stec |
author_sort |
Eva Csongradi |
title |
Renal Inhibition of Heme Oxygenase-1 Increases Blood Pressure in Angiotensin II-Dependent Hypertension |
title_short |
Renal Inhibition of Heme Oxygenase-1 Increases Blood Pressure in Angiotensin II-Dependent Hypertension |
title_full |
Renal Inhibition of Heme Oxygenase-1 Increases Blood Pressure in Angiotensin II-Dependent Hypertension |
title_fullStr |
Renal Inhibition of Heme Oxygenase-1 Increases Blood Pressure in Angiotensin II-Dependent Hypertension |
title_full_unstemmed |
Renal Inhibition of Heme Oxygenase-1 Increases Blood Pressure in Angiotensin II-Dependent Hypertension |
title_sort |
renal inhibition of heme oxygenase-1 increases blood pressure in angiotensin ii-dependent hypertension |
publisher |
Hindawi Limited |
series |
International Journal of Hypertension |
issn |
2090-0384 2090-0392 |
publishDate |
2012-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2012/497213 |
work_keys_str_mv |
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