Document Detail


Endothelial control of the pulmonary circulation in normal and chronically hypoxic rats.
MedLine Citation:
PMID:  8246176     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. The effect of blockade of nitric oxide synthesis in pulmonary endothelium by two L-arginine analogues was tested in isolated blood-perfused lungs of normal rats and rats exposed chronically to 10% O2. 2. In both groups of rats the analogues (N-monomethyl-L-arginine (L-NMMA) and N-nitro-L-arginine methyl ester (L-NAME)) enhanced hypoxic vasoconstriction. In normal rats, with rare exceptions, these analogues had little or no effect on pulmonary artery pressure (Ppa) at constant blood flow during normoxia. However, chronically hypoxic rats have pulmonary hypertension and in these rats the analogues always raised Ppa; the rise in Ppa after L-NMMA but not L-NAME could be partially reversed by L-arginine. L-NAME was more potent than L-NMMA. 3. To see whether the difference between rat groups was due to the high Ppa in chronically hypoxic rats, in control rats we raised Ppa passively by lung inflation to values higher than found in chronically hypoxic rats. L-NAME did not alter the effects of lung inflation on Ppa. 4. Ppa was also raised passively by plotting pressure-flow lines up to high flow rates; the lines were changed minimally by both analogues in control rats but in chronically hypoxic rats the lines were raised to higher pressures and steepened substantially. 5. In control rats, during vasoconstriction caused by hypoxia, endothelin 1 and almitrine, L-NAME caused further rises in pressure. We conclude that a stimulus for nitric oxide release in control rats is the narrowing of vessels caused by vasoconstriction rather than passive increases in intravascular pressure. 6. In chronically hypoxic rats arterioles are narrowed by growth of new muscle and there is some muscle tone even in normoxia. Thus narrowing of the vascular lumen is the stimulus common to both groups of rats which leads to nitric oxide synthesis and attenuation of Ppa by a negative feedback process. Narrowing is associated with a large increase in shear stress due to two factors; the pressure drop along a vessel segment is increased and the surface area of the lining of the affected segment is decreased. 7. Atrial natriuretic peptide caused dose-dependent pulmonary vasodilation in both rat groups but had a greater effect in chronically hypoxic rats. The action persisted and was enhanced after blockade of NO synthesis.
Authors:
G Barer; C Emery; A Stewart; D Bee; P Howard
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of physiology     Volume:  463     ISSN:  0022-3751     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  1993 Apr 
Date Detail:
Created Date:  1993-12-30     Completed Date:  1993-12-30     Revised Date:  2010-08-25    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1-16     Citation Subset:  IM    
Affiliation:
Department of Medicine and Pharmacology, University of Sheffield, Royal Hallamshire Hospital.
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MeSH Terms
Descriptor/Qualifier:
Almitrine / pharmacology
Animals
Anoxia / physiopathology*
Arginine / analogs & derivatives,  pharmacology
Atrial Natriuretic Factor / pharmacology
Blood Pressure / drug effects,  physiology
Chronic Disease
Endothelins / pharmacology
Endothelium, Vascular / physiology*
Male
NG-Nitroarginine Methyl Ester
Nitric Oxide / antagonists & inhibitors,  metabolism
Pulmonary Circulation / physiology*
Rats
Rats, Wistar
Respiration / physiology
Vasoconstriction / drug effects
omega-N-Methylarginine
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Endothelins; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; 27469-53-0/Almitrine; 50903-99-6/NG-Nitroarginine Methyl Ester; 74-79-3/Arginine; 85637-73-6/Atrial Natriuretic Factor
Comments/Corrections

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