Kidney Specific Induction of HO-1 Prevents Angiotensin II Hypertension

The main goal of this study was to determine if kidney specific induction of heme oxygenase-1 (HO-1) can prevent the development of Ang-II dependent hypertension. To test this hypothesis, intrarenal medullary interstitial catheters (IRMI) were implanted into the left kidney of uninephrectomized mice. Infusion of cobalt protoporphyrin (CoPP; 250 μg/ml; at 50 μl/hr for 48hrs) resulted in significant induction of HO-1 in the renal medulla when examined 2 weeks after the infusion with no induction observed in other organs such as the heart or liver. Next, we examined the effect of renal specific induction of HO-1 on the development of Ang II dependent hypertension. CoPP or Vehicle (0.1 M NaOH, pH 8.3) was infused as indicated above 2 days prior to implantation of an osmotic minipump which delivered Ang II or saline vehicle at a rate of 1 μg/kg/min. Mean arterial pressure (MAP) was measured in conscious, unrestrained mice for 3 consecutive days starting on day 7 after implantation of the minipumps. MAP averaged 114± 5, 122± 4, 162 ± 2 and 125 ± 6 mmHg in Vehicle, IRMI CoPP, Ang II and Ang II + IRMI CoPP treated mice respectively (n=6 or 7). These results demonstrate that kidney specific induction of HO-1 prevents the development of Ang II dependent hypertension and that induction of HO-1 in the kidney may be the mechanism by which systemic delivery of CoPP lowers blood pressure in Ang-II dependent hypertension.