Document Detail

HO-1 induction lowers blood pressure and superoxide production in the renal medulla of angiotensin II hypertensive mice.
MedLine Citation:
PMID:  17194725     Owner:  NLM     Status:  MEDLINE    
Heme oxygenase-1 (HO-1) induction can attenuate the development of angiotensin II (ANG II)-dependent hypertension. However, the mechanism by which HO-1 lowers blood pressure in this model is not clear. The goal of this study was to test the hypothesis that induction of HO-1 in the kidney can attenuate the increase in reactive oxygen species (ROS) generation in the kidney that occurs during ANG II-dependent hypertension. Mice were divided into four groups, control (Con), cobalt protoporphyrin (CoPP), ANG II, and ANG II + CoPP. CoPP treatment (50 mg/kg) was administered in a single subcutaneous injection 2 days prior to implantation of an osmotic minipump that infused ANG II at a rate of 1 microg x kg(-1) x min(-1). At the end of this period, mean arterial blood pressure (MAP) averaged 93 +/- 5, 90 +/- 5, 146 +/- 8, and 105 +/- 6 mmHg in Con, CoPP-, ANG II-, and ANG II + CoPP-treated mice. To determine whether HO-1 induction resulted in a decrease in ANG II-stimulated ROS generation in the renal medulla, superoxide production was measured. Medullary superoxide production was increased by ANG II infusion and normalized in mice pretreated with CoPP. The reduction in ANG II-mediated superoxide production in the medulla with CoPP was associated with a decrease in extracellular superoxide dismutase protein but an increase in catalase protein and activity. These results suggest that reduction in superoxide and possibly hydrogen peroxide production in the renal medulla may be a potential mechanism by which induction of HO-1 with CoPP lowers blood pressure in ANG-II dependent hypertension.
Trinity Vera; Silvia Kelsen; Licy L Yanes; Jane F Reckelhoff; David E Stec
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-12-28
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  292     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-04     Completed Date:  2007-05-23     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1472-8     Citation Subset:  IM    
Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216-4505, USA.
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MeSH Terms
Angiotensin II / administration & dosage,  pharmacology*
Blood Pressure / physiology*
Enzyme Induction
Heme Oxygenase-1 / biosynthesis*,  genetics
Hypertension, Renal / chemically induced,  metabolism*,  physiopathology
Implants, Experimental
Infusions, Intravenous
Injections, Subcutaneous
Kidney Medulla* / enzymology,  metabolism
Mice, Inbred C57BL
Protoporphyrins / administration & dosage,  pharmacology
Superoxides / metabolism*
Vasoconstrictor Agents / administration & dosage,  pharmacology*
Grant Support
Reg. No./Substance:
0/Protoporphyrins; 0/Vasoconstrictor Agents; 11062-77-4/Superoxides; 11128-99-7/Angiotensin II; 14325-03-2/cobaltiprotoporphyrin; EC Oxygenase-1

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