renal inhibition of heme oxygenase-1 increases blood pressure in angiotensin ii-dependent hypertension肾抑制血红素oxygenase-1血压增加血管紧张素ii-dependent高血压.pdf

Hindawi Publishing Corporation International Journal of Hypertension Volume 2012, Article ID 497213, 8 pages doi:10.1155/2012/497213 Research Article Renal Inhibition of Heme Oxygenase-1 Increases Blood Pressure in Angiotensin II-Dependent Hypertension Eva Csongradi,1, 2 Megan V. Storm,1 and David E. Stec1 1 Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA 2 1st Department of Internal Medicine, Medical and Health Sciences Center, University of Debrecen, 4032 Debrecen, Hungary Correspondence should be addressed to David E. Stec, dstec@ Received 8 August 2011; Accepted 6 September 2011 Academic Editor: David Sacerdoti Copyright © 2012 Eva Csongradi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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). Inhi