Document Detail

Induction of heme oxygenase-1 and stimulation of cGMP production by hemin in aortic tissues from hypertensive rats.
MedLine Citation:
PMID:  12506017     Owner:  NLM     Status:  MEDLINE    
Heme oxygenase (HO) and carbon monoxide (CO) have been implicated in the modulation of various cardiovascular functions including blood pressure (BP) regulation. Up-regulating the HO/CO system lowers BP in young (8-week-old) but not in adult (20-week-old) spontaneously hypertensive rats (SHRs). The mechanisms for this selective effect are largely unknown. We investigated the effects of HO-1 inducer, hemin, on the HO/CO-soluble gyanylyl cyclase (sGC)/cGMP system in the aorta of prehypertensive (4-week-old) young and adult SHRs as well as age-matched Wistar-Kyoto rats (WKYs). Reduced expressions of HO-1, HO-2, and sGC proteins associated with depressed HO activity and cGMP levels were detected in young SHRs. These deficiencies were significantly reversed by hemin treatment. Macrophage infiltration of vascular tissues was more significant in adult SHRs than adult WKYs, but invisible in young SHRs and WKYs. Hemin treatment did not alter macrophage infiltration of vascular tissues in young SHRs. The same hemin administration resulted in a significant decrease in BP (from 148.6 +/- 3.2 to 125.8 +/- 2.6 mmHg, P <.01) in young SHRs, but not in prehypertensive or adult SHRs or WKYs of all ages. The HO inhibitor zinc protoporphyrin abrogated the hemin effect in young SHRs. Aortic tissues became desensitized to YC-1, an activator sGC, in adult SHRs. Thus, in young SHRs the expression and function of the HO/CO-sGC/cGMP system were suppressed, constituting a pathogenic mechanism for the development of hypertension. In adult SHRs, the HO/CO-sGC/cGMP system appeared normal, but desensitization of the sGC/cGMP pathway caused hypertension to prevail.
Joseph Fomusi Ndisang; Lingyun Wu; Weimin Zhao; Rui Wang
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2002-12-27
Journal Detail:
Title:  Blood     Volume:  101     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-06     Completed Date:  2003-07-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3893-900     Citation Subset:  AIM; IM    
Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada.
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MeSH Terms
Aorta / drug effects,  metabolism*
Blood Pressure
Cyclic GMP / metabolism*
Enzyme Induction / drug effects
Guanylate Cyclase / biosynthesis
Heme Oxygenase (Decyclizing) / biosynthesis*
Heme Oxygenase-1
Hemin / pharmacology*
Hypertension / enzymology,  genetics,  physiopathology*
Muscle, Smooth, Vascular / drug effects,  metabolism*
Rats, Inbred SHR
Rats, Inbred WKY
Reg. No./Substance:
16009-13-5/Hemin; 7665-99-8/Cyclic GMP; EC Oxygenase (Decyclizing); EC Oxygenase-1; EC oxygenase-2; EC Cyclase

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