Document Detail


Heme oxygenase-1-derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo.
MedLine Citation:
PMID:  9734480     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The enzyme heme oxygenase, which exists in inducible (HO-1) and constitutive (HO-2) isoforms, catalyzes the degradation of heme to biliverdin and CO in mammalian tissues. CO has been implicated in the control of vascular tone in a manner similar to that for NO. In the present study, we investigated the contribution of the heme oxygenase/CO pathway to the modulation of acute hypertensive responses in vivo induced by (1) alphaalphaHb, a chemically modified hemoglobin known to scavenge NO, and (2) NG-nitro-L-arginine methyl ester (L-NAME), a competitive NOS inhibitor. Experiments were carried out in conscious rats in which femoral arteries and veins were surgically catheterized 1 or 5 days before treatment with the vasoconstrictor agents. Intravenous infusion of alphaalphaHb (8% solution) or L-NAME (30 micromol/kg) [corrected] produced an acute and significant increase in mean arterial pressure (P<0.05) in rats at 5 days after catheter implantation. In contrast, no change in blood pressure was observed when alphaalphaHb or L-NAME was infused 1 day after the surgical intervention. The suppression of the hypertensive response observed at 1 day after surgery correlated with a significant (P<0.05) HO-1 expression in aorta, heart, and liver as well as increased aortic CO production and cGMP levels. At 1 day after surgery, pretreatment of animals with the heme oxygenase inhibitor zinc protoporphyrin IX (50 micromol/kg IP) markedly decreased aortic CO and cGMP levels and completely restored the vasoconstrictor effects of both alphaalphaHb and L-NAME. These results provide evidence for a crucial role of the heme oxygenase/CO pathway in the regulation of blood pressure under stress conditions in vivo.
Authors:
R Motterlini; A Gonzales; R Foresti; J E Clark; C J Green; R M Winslow
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  83     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-09-24     Completed Date:  1998-09-24     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  568-77     Citation Subset:  IM    
Affiliation:
Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex, UK. r.motterlini@ic.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Animals
Blood Pressure / physiology
Carbon Monoxide / metabolism*
Depression, Chemical
Enzyme Inhibitors / pharmacology*
Heme Oxygenase (Decyclizing) / metabolism*
Heme Oxygenase-1
Hemoglobins / pharmacology
Hypertension / prevention & control*
Male
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide Synthase / antagonists & inhibitors*
Postoperative Complications / prevention & control
Rats
Rats, Sprague-Dawley
Stress, Physiological / physiopathology*
Up-Regulation
Grant Support
ID/Acronym/Agency:
P01 HL-48018/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Hemoglobins; 50903-99-6/NG-Nitroarginine Methyl Ester; 630-08-0/Carbon Monoxide; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.99.3/Heme Oxygenase (Decyclizing); EC 1.14.99.3/Heme Oxygenase-1
Comments/Corrections
Erratum In:
Circ Res 1998 Dec 14-28;83(12):1289

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