Document Detail

Alterations in heme oxygenase/carbon monoxide system in pulmonary arteries in hypertension.
MedLine Citation:
PMID:  12709586     Owner:  NLM     Status:  MEDLINE    
Enhancement of the heme oxygenase/carbon monoxide (HO/CO) system has been shown to lower blood pressure (BP) in young (8 weeks), but not in adult (20 weeks) spontaneously hypertensive (SHR) rats. The reasons for this selective effect still remain puzzling. We investigated the effects of hemin on the HO/CO system of the pulmonary artery (PA) in SHR and Wistar-Kyoto (WKY) rats at different ages and evaluated the hemin-dependent changes in sGC and cGMP pathways. Hemin administration resulted in an evident reduction of BP (from 148.6 +/- 3.2 to 125.8 +/- 2.6 mmHg, P < 0.01) in young, but not in prehypertensive (4 weeks) or adult SHR or WKY rats at all ages. Coadministration of the HO inhibitor, chromium mesoporphyrin, with hemin, cancelled the BP-lowering effect of hemin. Remarkably, lower expression levels of HO-1, HO-2, and sGC paralleled with reduced HO activity and cGMP content were observed in PA from 8-week SHR rats, but not from adult SHR or WKY rats of all ages. Interestingly, hemin treatment restored these deficiencies, although the expression level of non-inducible HO-2 protein remained unchanged. We conclude that in young and prehypertensive SHR rats, an impaired HO/CO-sGC/cGMP system in the PA might be indicative of the pathogenesis and development of hypertension. In contrast, the HO/CO system in the PA of adult SHR rats was upregulated as a compensatory reaction to elevated BP and desensitization of the downstream targets of the sGC/cGMP pathway occurred.
Joseph Fomusi Ndisang; Rui Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  228     ISSN:  1535-3702     ISO Abbreviation:  Exp. Biol. Med. (Maywood)     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-04-23     Completed Date:  2003-06-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  557-63     Citation Subset:  IM    
Department of Physiology, University of Saskatchewan, Saskatchewan, Canada, S7N 5E5.
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MeSH Terms
Aging / physiology
Carbon Monoxide / metabolism*
Cyclic GMP / metabolism
Guanylate Cyclase
Heme Oxygenase (Decyclizing) / metabolism*
Heme Oxygenase-1
Hemin / metabolism*
Hypertension / metabolism*
Pulmonary Artery / metabolism*
Rats, Inbred SHR
Rats, Inbred WKY
Receptors, Cytoplasmic and Nuclear / metabolism
Reg. No./Substance:
0/Receptors, Cytoplasmic and Nuclear; 16009-13-5/Hemin; 630-08-0/Carbon Monoxide; 7665-99-8/Cyclic GMP; EC Oxygenase (Decyclizing); EC Oxygenase-1; EC oxygenase-2; EC Cyclase; EC guanylyl cyclase
Erratum In:
Exp Biol Med (Maywood). 2003 Jun;228(6):767

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