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.