Title: Renal Medullary Infusion of CoPP Prevents Angiotensin‐II Dependent Hypertension in Mice
Abstract: Several studies have established systemic induction of Heme Oxygenase-1 (HO-1) as a viable means of attenuating the development of hypertension in several experimental models. However, the precise mechanism behind the anti-hypertensive actions of HO-1 induction is still unclear. In this study, we tested the hypothesis that kidney specific induction of HO-1 can prevent the development of Ang-II dependent hypertension. To test this hypothesis, renal medullary interstitial catheters were implanted into the left kidney of uninephrectomized mice. Infusion of a known inducer of HO-1, cobalt protoporphyrin (CoPP; 250 μg/ml; at 50 μl/hr for 48hrs), resulted in significant induction of HO-1 mainly in the renal medulla when examined 2 weeks after the infusion with no induction observed in other organs such as the brain, heart, and liver. Next, we examined the effect of this approach of inducing 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 at a rate of 1 μg/kg/min. Mean arterial pressure (MAP) was measured in conscious, unrestrained mice for 3 consecutive days starting 7 days after the implantation of the Ang II minipumps. MAP averaged 112 ± 4, 121 ± 4, 162 ± 2 and 126 ± 6 mmHg in Vehicle + Vehicle, CoPP + Vehicle, Vehicle + Ang II and CoPP + Ang II treated mice respectively (n=6). These results suggest that renal medullary infusion of CoPP to induce HO-1 specifically in the kidneys can prevent the development of Ang II dependent hypertension in mice. Induction of HO-1 in the renal medulla may be the mechanism by which systemic delivery of CoPP lowers blood pressure in Ang-II dependent hypertension.
Publication Year: 2007
Publication Date: 2007-01-01
Language: en
Type: article
Indexed In: ['crossref']
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