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This Article Full Text Full Text (PDF) All Versions of this Article: 574/2/615    most recent jphysiol.2006.107060v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Houweling, B. Articles by Duncker, D. J. Search for Related Content PubMed PubMed Citation Articles by Houweling, B. Articles by Duncker, D. J. Related Collections Integrative

¹ Experimental Cardiology, Thoraxcentre²Internal Medicine, Cardiovascular Research Institute COEUR, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands

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 0.05). MI increased pulmonary arterial pressure and PVR both at rest and during exercise (both P 0.05). The increased pulmonary arterial pressure correlated with the increased plasma ET levels in resting MI swine (r = 0.71; P 0.01). Furthermore, the pulmonary vasoconstrictor response to ET-1 infusion was enhanced after MI (P 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 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 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.

(Received 8 February 2006; accepted after revision 11 May 2006; first published online 18 May 2006)
Corresponding author D. J. Duncker: Experimental Cardiology, Thoraxcentre, Erasmus MC, University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, the Netherlands. Email: d.duncker{at}erasmusmc.nl

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				D. Merkus, B. Houweling, V. J. de Beer, Z. Everon, and D. J. Duncker Alterations in endothelial control of the pulmonary circulation in exercising swine with secondary pulmonary hypertension after myocardial infarction J. Physiol., May 1, 2007; 580(3): 907 - 923. [Abstract] [Full Text] [PDF]