Document Detail


Inhibition of sustained hypoxic vasoconstriction by Y-27632 in isolated intrapulmonary arteries and perfused lung of the rat.
MedLine Citation:
PMID:  10960061     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have examined the effects of Y-27632, a specific inhibitor of Rho-activated kinases (ROCK I and ROCK II) upon sustained hypoxic pulmonary vasoconstriction (HPV) in both rat isolated small intrapulmonary arteries (IPA) and perfused rat lungs in situ. Y-27632 (100 nM - 3 microM) was found to cause a concentration-dependent inhibition of acute sustained HPV in rat IPA. Application of Y-27632 (10-600 nM) in perfused rat lungs caused no change in basal perfusion pressure, but was found to inhibit HPV in a concentration-dependent manner, resulting in complete ablation of the pressor response to hypoxia at a concentration of 600 nM. Furthermore, addition of Y-27632 at any point during hypoxia caused a reversal of HPV in perfused rat lungs. These results suggest that activation of Rho-associated kinase may be a pivotal step in the generation of sustained HPV.
Authors:
T P Robertson; M Dipp; J P Ward; P I Aaronson; A M Evans
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  131     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-11-03     Completed Date:  2000-11-03     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  5-9     Citation Subset:  IM    
Affiliation:
Department of Respiratory Medicine and Allergy, GKT School of Medicine, King's College London, Guy's Campus, London SE1 9RT. tom.robertson@kcl.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Amides / pharmacology*
Animals
Anoxia / physiopathology*
Calcium / metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology*
Intracellular Signaling Peptides and Proteins
Lung / drug effects*,  physiology
Male
Perfusion
Protein-Serine-Threonine Kinases / antagonists & inhibitors*,  physiology
Pulmonary Artery / drug effects*,  physiology
Pyridines / pharmacology*
Rats
Rats, Wistar
Vasoconstriction / drug effects*
rho-Associated Kinases
Chemical
Reg. No./Substance:
0/Amides; 0/Enzyme Inhibitors; 0/Intracellular Signaling Peptides and Proteins; 0/Pyridines; 138381-45-0/Y 27632; 7440-70-2/Calcium; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/rho-Associated Kinases
Comments/Corrections

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


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