Document Detail

Differential effect of cobalt protoporphyrin on distributions of heme oxygenase in renal structure and on blood pressure in SHR.
MedLine Citation:
PMID:  12699248     Owner:  NLM     Status:  MEDLINE    
Heme oxygenase (HO) is a microsomal enzyme that oxidatively cleaves heme to form biliverdin, releasing iron and carbon monoxide (CO). Thus, HO not only controls the availability of heme for the synthesis of hemeproteins but also generates CO, which binds to the heme moiety of hemoproteins, thereby affecting their enzymatic activity. The present study was undertaken to explore changes in the relative expression of renal HO-1 and HO-2 in response to modulators and the effect on blood pressure regulation in spontaneously hypertensive rats (SHR). Immunohistochemistry confirmed a cobalt protoporphyrin (CoPP)-mediated increase in HO-1 protein. After a single injection of CoPP (5 mg/100 gram body weight) in 7-week-old SHR, blood pressure significantly decreased (p<0.01) while renal HO activity increased 6-fold over controls. CoPP pretreatment deceased the levels of the renal cytochrome P450-derived arachidonic acid metabolite, 20-HETE, a powerful vasoconstrictor, by 65% in renal tissue. Western blot analysis demonstrated that CoPP significantly increased HO-1 protein expression in the cortex and outer medulla and, to a lesser degree, in the inner medulla of the rat kidney. HO-2 was constitutively expressed in all parts of the kidney, and did not significantly change after treatment with CoPP. These results indicate that selective induction of cortical and outer medullary HO-1 is associated with a decrease in 20-HETE and blood pressure, suggesting an important role for HO-1 activity in the regulation of urine volume, electrolyte excretion and blood pressure.
N G Abraham; F T Botros; R Rezzani; L Rodella; R Bianchi; A I Goodman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cellular and molecular biology (Noisy-le-Grand, France)     Volume:  48     ISSN:  0145-5680     ISO Abbreviation:  Cell. Mol. Biol. (Noisy-le-grand)     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2003-04-17     Completed Date:  2003-09-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9216789     Medline TA:  Cell Mol Biol (Noisy-le-grand)     Country:  France    
Other Details:
Languages:  eng     Pagination:  895-902     Citation Subset:  IM    
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
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MeSH Terms
Blood Pressure
Blotting, Northern
Blotting, Western
Cytochrome P-450 Enzyme System / metabolism
Heme Oxygenase (Decyclizing) / biosynthesis*,  metabolism
Heme Oxygenase-1
Hydroxyeicosatetraenoic Acids / pharmacology
Kidney / metabolism*,  physiology*
Kidney Medulla / metabolism
Microsomes / metabolism
Protein Isoforms
Protoporphyrins / pharmacology*
Rats, Inbred SHR
Vasoconstrictor Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Hydroxyeicosatetraenoic Acids; 0/Protein Isoforms; 0/Protoporphyrins; 0/Vasoconstrictor Agents; 14325-03-2/cobaltiprotoporphyrin; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid; 9035-51-2/Cytochrome P-450 Enzyme System; EC Oxygenase (Decyclizing); EC Oxygenase-1; EC oxygenase-2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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