Gene Targeting and Heme Oxygenase-1 Expression in Prevention of Hypertension Induced by Angiotensin II

The report by Vera et al1 that appears in this issuedemonstrates that the kidney-specific induction of heme oxygenase (HO)-1 prevents angiotensin (Ang) II hyperten-sion in CL57BL/6J mice. Kidney-specific induction of HO-1 was achieved by implanting intrarenal medullary interstitial catheters in the left kidney of uninephrectomized mice. Infusion of cobalt protoporphyrin, a known inducer of HO-1, produced a significant induction of HO-1 protein levels and increased HO activity largely in the renal medulla. Ang II–dependent hypertension was examined by measuring mean arterial pressure and was found to be attenuated in cobalt protoporphyrin–treated animals. The levels of heme, the substrate of HO, and superoxide were increased in Ang II–treated animal. These increases were blocked in cobalt protoporphyrin–treated animals. The authors conclude that the specific induction of renal HO-1 is responsible fo