on August 11, 2008
Published online before print August 11, 2008, doi: 10.1161/HYPERTENSIONAHA.108.114884
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 14, 2008
From the Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson. * To whom correspondence should be addressed. E-mail: dstec{at}physiology.umsmed.edu.
Abstract—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.
Revised on April 28, 2008
Kidney-Specific Induction of Heme Oxygenase-1 Prevents Angiotensin II Hypertension
Trinity Vera;
Key words: heme oxygenase-1 • kidney • angiotensin II • hypertension • cobalt protoporphyrin
Related Article:
Hypertension 2008 52: 618-620.
This article has been cited by other articles:
 |
|
 |
|
  D. E. Stec, T. Vera, M. V. Storm, G. R. McLemore Jr, and M. J. Ryan Blood pressure and renal blow flow responses in heme oxygenase-2 knockout mice Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2009; 297(6): R1822 - R1828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Young, M. V. Storm, J. S. Speed, S. Kelsen, C. V. Tiller, T. Vera, H. A. Drummond, and D. E. Stec Inhibition of biliverdin reductase increases ANG II-dependent superoxide levels in cultured renal tubular epithelial cells Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1546 - R1553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Abraham, J. Cao, D. Sacerdoti, X. Li, and G. Drummond Heme oxygenase: the key to renal function regulation Am J Physiol Renal Physiol, November 1, 2009; 297(5): F1137 - F1152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Vera, J. P. Granger, and D. E. Stec Inhibition of bilirubin metabolism induces moderate hyperbilirubinemia and attenuates ANG II-dependent hypertension in mice Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R738 - R743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Danziger Use of Protoporphyrins to Evaluate Heme Oxygenase Problematical Hypertension, February 1, 2009; 53(2): e15 - e15. [Full Text] [PDF]
|
|
|
|
|
|
T. Vera, S. Kelsen, and D. E. Stec Response to Use of Protoporphyrins to Evaluate Heme Oxygenase Problematical Hypertension, February 1, 2009; 53(2): e16 - e16. [Full Text] [PDF]
|
|
|
|
|
|
N. G. Abraham Gene Targeting and Heme Oxygenase-1 Expression in Prevention of Hypertension Induced by Angiotensin II Hypertension, October 1, 2008; 52(4): 618 - 620. [Full Text] [PDF]
|
|