Document Detail


Heme Oxygenase-1 Overexpression Fails to Attenuate Hypertension when the Nitric Oxide Synthase System Is Not Fully Operative.
MedLine Citation:
PMID:  21646819     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Heme oxygenase (HO) is an enzyme that is involved in numerous secondary actions. One of its products, CO, seems to have an important but unclear role in blood pressure regulation. CO exhibits a vasodilator action through the activation of soluble guanylate cyclase and the subsequent production of cyclic guanosine monophosphate (cGMP). The aim of the present study was to determine whether pathological and pharmacological HO-1 overexpression has any regulatory role on blood pressure in a renovascular model of hypertension. We examined the effect of zinc protoporyphyrin IX (ZnPP-IX) administration, an inhibitor of HO activity, on mean arterial pressure (MAP) and heart rate in sham-operated and aorta-coarcted (AC) rats and its interaction with the nitric oxide synthase (NOS) pathway. Inhibition of HO increased MAP in normotensive rats with and without hemin pretreatment but not in hypertensive rats. Pretreatment with NG-nitro-L-arginine methyl ester blocked the pressor response to ZnPP-IX, suggesting a key role of NOS in the cardiovascular action of HO inhibition. In the same way, AC rats, an experimental model of hypertension with impaired function and low expression of endothelial NOS (eNOS), did not show any cardiovascular response to inhibition or induction of HO. This finding suggests that eNOS was necessary for modulating the CO response in the hypertensive group. In conclusion, the present study suggests that HO regulates blood pressure through CO only when the NOS pathway is fully operative. In addition, chronic HO induction fails to attenuate the hypertensive stage induced by coarctation as a consequence of the impairment of the NOS pathway.
Authors:
Ariel H Polizio; Diego M Santa-Cruz; Karina B Balestrasse; Mariela M Gironacci; Facundo M Bertera; Christian Höcht; Carlos A Taira; Maria L Tomaro; Susana B Gorzalczany
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-03
Journal Detail:
Title:  Pharmacology     Volume:  87     ISSN:  1423-0313     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0152016     Medline TA:  Pharmacology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  341-349     Citation Subset:  -    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Affiliation:
Department of Pharmacology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
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