Document Detail


A heme oxygenase product, presumably carbon monoxide, mediates a vasodepressor function in rats.
MedLine Citation:
PMID:  7843765     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heme oxygenase is a mammalian enzyme that converts heme to biliverdin and carbon monoxide. Carbon monoxide activates soluble guanylate cyclase and relaxes vascular smooth muscle, and it has been implicated as a potential neuromessenger. The regulatory functions of endogenous carbon monoxide on hemodynamics are not known. Zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) inhibits heme oxygenase in rats and thus permits assessment of the hemodynamic response to inhibition of endogenous carbon monoxide synthesis. In chronically instrumented, awake male Sprague-Dawley rats, ZnDPBG (45 mumol/kg IP) increased mean arterial pressure (19 +/- 2%, P < .05) and total peripheral resistance (47 +/- 4%, P < .05), decreased cardiac output (-16 +/- 2%, P < .05), but did not affect heart rate. Another heme oxygenase inhibitor, zinc protoporphyrin IX (45 mumol/kg IP), also increased arterial pressure (17 +/- 5%, P < .05), with no effect on heart rate. In contrast, neither the nonmetallic deuteroporphyrin 2,4-bis glycol (45 mumol/kg IP) nor bilverdin (45 mumol/kg IP) had any effect on blood pressure or heart rate. These findings suggest that ZnDPBG and zinc protoporphyrin IX increase arterial pressure by inhibiting heme oxygenase activity. After pretreatment with chlorisondamine (5 mg/kg IP) or prazosin (5 mg/kg IP) to inhibit autonomic ganglionic or alpha 1-adrenoceptor functions, respectively, ZnDPBG did not affect arterial pressure or heart rate. This suggests that ZnDPBG-induced increases in blood pressure rely on autonomic nervous function. We conclude that the pressor response to heme oxygenase inhibitors results from withdrawal of the inhibitory influence of endogenous carbon monoxide on a pressor mechanism mediated by the autonomic nervous system.
Authors:
R A Johnson; M Lavesa; B Askari; N G Abraham; A Nasjletti
Related Documents :
11847195 - Cardiovascular effects of overexpression of endothelial nitric oxide synthase in the ro...
17266625 - Analogy of cardiac and renal complications in essential hypertension and aged shr or l-...
18635755 - Direct and acute cardiotoxic effects of ultrafine air pollutants in spontaneously hyper...
3652625 - Disturbance of acid-base balance in the young spontaneously hypertensive rat.
23194285 - Treatment with the cytochrome p450 ω-hydroxylase inhibitor het0016 attenuates cerebrova...
17980485 - Calculation of the upper flammability limit of methane/air mixtures at elevated pressur...
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  25     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1995 Feb 
Date Detail:
Created Date:  1995-03-06     Completed Date:  1995-03-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  166-9     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, New York Medical College, Valhalla 10595.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / physiology*
Carbon Monoxide / metabolism*
Chlorisondamine / pharmacology
Deuteroporphyrins / pharmacology
Heart Rate / drug effects
Heme Oxygenase (Decyclizing) / antagonists & inhibitors,  metabolism*
Hemodynamics / drug effects
Male
Prazosin / pharmacology
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
5PO1 HL-34300/HL/NHLBI NIH HHS; HL-18579/HL/NHLBI NIH HHS; HL-36670/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Deuteroporphyrins; 119700-81-1/zinc deuteroporphyrin IX 2,4-bis(glycol); 19216-56-9/Prazosin; 630-08-0/Carbon Monoxide; 7701-62-4/Chlorisondamine; EC 1.14.99.3/Heme Oxygenase (Decyclizing)

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


Previous Document:  Resetting blood pressure in spontaneously hypertensive rats. The role of bradykinin.
Next Document:  Production of aldosterone in isolated rat blood vessels.