Document Detail

Inhalation of the ETA receptor antagonist LU-135252 selectively attenuates hypoxic pulmonary vasoconstriction.
MedLine Citation:
PMID:  18077516     Owner:  NLM     Status:  MEDLINE    
Endogenous endothelin (ET)-1 modulates hypoxic pulmonary vasoconstriction (HPV). Accordingly, intravenously applied ET(A) receptor antagonists reduce HPV, but this is accompanied by systemic vasodilation. We hypothesized that inhalation of an ET(A) receptor antagonist might act selectively on the pulmonary vasculature and investigated the effects of aerosolized LU-135252 in an experimental model of HPV. Sixteen piglets (weight: 25 +/- 1 kg) were anesthetized and mechanically ventilated at an inspiratory oxygen fraction (Fi(O(2))) of 0.3. After 1 h of hypoxia at Fi(O(2)) 0.15, animals were randomly assigned either to receive aerosolized LU-135252 as bolus (0.3 mg/kg for 20 min; n = 8, LU group), or to receive aerosolized saline (n = 8, controls). In all animals, hypoxia significantly increased mean pulmonary arterial pressure (32 +/- 1 vs. 23 +/- 1 mmHg; P < 0.01; means +/- SE) and increased arterial plasma ET-1 (0.52 +/- 0.04 vs. 0.37 +/- 0.05 fmol/ml; P < 0.01) compared with mild hyperoxia at Fi(O(2)) 0.3. Inhalation of LU-135252 induced a significant and sustained decrease in mean pulmonary arterial pressure compared with controls (LU group: 27 +/- 1 mmHg; controls: 32 +/- 1 mmHg; values at 4 h of hypoxia; P < 0.01). In parallel, mean systemic arterial pressure and cardiac output remained stable and were not significantly different from control values. Consequently, in our experimental model of HPV, the inhaled ET(A) receptor antagonist LU-135252 induced selective pulmonary vasodilation without adverse systemic hemodynamic effects.
Bodil Petersen; Maria Deja; Roland Bartholdy; Bernd Donaubauer; Sven Laudi; Roland C E Francis; Willehad Boemke; Udo Kaisers; Thilo Busch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-12
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  294     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-31     Completed Date:  2008-03-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R601-5     Citation Subset:  IM    
Klinik und Poliklinik fuer Anaesthesiologie und Intensivtherapie, Universitaetsklinikum Leipzig, Liebigstrasse 20, Leipzig, Germany.
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MeSH Terms
Administration, Inhalation
Anoxia / drug therapy*
Blood Pressure / drug effects
Disease Models, Animal
Hypertension, Pulmonary / drug therapy*
Phenylpropionates / pharmacology*
Pulmonary Artery / drug effects,  physiology
Pulmonary Circulation / drug effects
Pyrimidines / pharmacology*
Receptor, Endothelin A / antagonists & inhibitors*,  metabolism
Vasoconstriction / drug effects*
Reg. No./Substance:
0/LU 135252; 0/Phenylpropionates; 0/Pyrimidines; 0/Receptor, Endothelin A

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

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