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(Hypertension. 2008;52:660.)
© 2008 American Heart Association, Inc.

Original Articles

Kidney-Specific Induction of Heme Oxygenase-1 Prevents Angiotensin II Hypertension

Trinity Vera; Silvia Kelsen; David E. Stec

From the Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson.

Correspondence to David E. Stec, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505. E-mail dstec{at}physiology.umsmed.edu

The main goal of this study was to determine whether kidney-specific induction of heme oxygenase-1 (HO-1) can prevent the development of angiotensin (Ang) II–dependent hypertension. To test this hypothesis, intrarenal medullary interstitial catheters were implanted into the left kidney of uninephrectomized mice. Infusion of cobalt protoporphyrin (CoPP; 250 µg/mL; at 50 µL/h for 48 hours) 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 mol/L NaOH [pH 8.3]) was infused as indicated above 2 days before implantation of an osmotic minipump, which delivered Ang II or saline vehicle at a rate of 1 µg/kg per minute. Mean arterial pressure was measured in conscious, unrestrained mice for 3 consecutive days starting on day 7 after implantation of the minipumps. Mean arterial pressure averaged 114±5, 122±4, 162±2, and 125±6 mm Hg in vehicle-, intrarenal medullary interstitial CoPP–, Ang II-, and Ang II + intrarenal medullary interstitial 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.

Key Words: heme oxygenase-1 • kidney • angiotensin II • hypertension • cobalt protoporphyrin

Related Article:

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

Nader G. Abraham
Hypertension 2008 52: 618-620. [Extract] [Full Text] [PDF]

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