Document Detail

Role of endothelin receptor activation in secondary pulmonary hypertension in awake swine after myocardial infarction.
MedLine Citation:
PMID:  16709643     Owner:  NLM     Status:  MEDLINE    
We previously observed that pulmonary hypertension secondary to myocardial infarction (MI) in swine is characterized by elevated plasma endothelin (ET) levels and pulmonary vascular resistance (PVR). Consequently, we tested the hypothesis that an increased ET-mediated vasoconstrictor influence contributes to secondary pulmonary hypertension after MI and investigated the involvement of ET(A) and ET(B) receptor subtypes. Chronically instrumented swine with (MI swine; n = 25) or without (normal swine; n = 19) MI were studied at rest and during treadmill exercise (up to 4 km h(-1)), in the absence and presence of the ET(A) antagonist EMD 122946 or the mixed ET(A)/ET(B) antagonist tezosentan. In normal swine, exercise caused a small decrease in PVR. ET(A) blockade had no effect on PVR at rest or during exercise. Conversely, ET(A)/ET(B) blockade decreased PVR but only during exercise (at 4 km h(-1), from 3.0 +/- 0.1 to 2.3 +/- 0.1 mmHg min l(-1); P <or= 0.05). MI increased pulmonary arterial pressure and PVR both at rest and during exercise (both P <or= 0.05). The increased pulmonary arterial pressure correlated with the increased plasma ET levels in resting MI swine (r = 0.71; P <or= 0.01). Furthermore, the pulmonary vasoconstrictor response to ET-1 infusion was enhanced after MI (P <or= 0.05). ET(A)/ET(B) blockade decreased PVR in MI swine from 3.6 +/- 0.3 to 3.1 +/- 0.5 mmHg min l(-1) at rest and from 3.4 +/- 0.3 to 2.4 +/- 0.2 mmHg min l(-1) during exercise at 4 km h(-1) (both P <or= 0.05). This increased response to mixed ET(A)/ET(B) blockade in MI compared to normal swine appeared to be the result of an increased ET(A)-mediated vasoconstriction, as ET(A) blockade decreased PVR in MI swine from 3.4 +/- 0.4 to 2.8 +/- 0.2 mmHg min l(-1) at rest and from 3.1 +/- 0.3 to 2.6 +/- 0.2 mmHg min l(-1) at 4 km h(-1) (both P <or= 0.05). In conclusion, increased plasma ET levels together with increased pulmonary resistance vessel responsiveness to ET result in an exaggerated pulmonary vasoconstrictor influence of ET in swine with a recent MI. This vasoconstrictor influence is the result of an emergent tonic ET(A)-mediated vasoconstriction in addition to the exercise-induced ET(B)-mediated vasoconstriction that is already present in normal swine.
Birgit Houweling; Daphne Merkus; Oana Sorop; Frans Boomsma; Dirk J Duncker
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-18
Journal Detail:
Title:  The Journal of physiology     Volume:  574     ISSN:  0022-3751     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-17     Completed Date:  2006-09-18     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  615-26     Citation Subset:  IM    
Experimental Cardiology, Thoraxcentre, Erasmus MC, University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, the Netherlands.
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MeSH Terms
Blood Pressure / drug effects,  physiology
Consciousness / physiology*
Endothelin-1 / pharmacology
Hemodynamics / drug effects,  physiology
Hypertension, Pulmonary / blood,  etiology*,  physiopathology*
Myocardial Infarction / blood,  complications*,  physiopathology*
Physical Conditioning, Animal / physiology
Pulmonary Circulation / drug effects,  physiology
Pyridines / pharmacology
Receptors, Endothelin / antagonists & inhibitors,  blood,  physiology*
Rest / physiology
Tetrazoles / pharmacology
Vasoconstriction / physiology
Vasodilator Agents / pharmacology
Reg. No./Substance:
0/Endothelin-1; 0/Pyridines; 0/Receptors, Endothelin; 0/Tetrazoles; 0/Vasodilator Agents; 64J9J55263/tezosentan

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