Alterations in Endothelial Control of the Pulmonary Circulation in Exercising Swine with Secondary Pulmonary Hypertension After Myocardial Infarction.
From: Experimental Cardiology, Thoraxcentre, Cardiovascular Research School COEUR, Erasmus MC, University Medical Centre Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. d.merkus@erasmusmc.nl
The Journal of physiology
- Publish Date: May 2007
- ISSN: 0022-3751
- Volume: 580
- Issue: Pt.3
- Pages: 907-23
- Medium: Print
- Language: English
- Citation (JAMA): Merkus Daphne, Houweling Birgit, de Beer Vincent J, et al. Alterations in Endothelial Control of the Pulmonary Circulation in Exercising Swine with Secondary Pulmonary Hypertension After Myocardial Infarction.. J. Physiol. (Lond.) May 2007;580:907-23
Abstract
Secondary pulmonary hypertension after myocardial infarction (MI) has been associated with endothelial dysfunction and activation of the endothelin (ET) system. Here, we investigated whether an increased ET-mediated pulmonary vasoconstrictor influence contributes to pulmonary hypertension after MI, and whether this increased ET vasoconstriction is caused by impaired nitric oxide (NO) and prostanoid production. For this purpose, chronically instrumented swine with and without MI ran on a treadmill at 0-4 km h(-1). Mixed ET(A)/ET(B) receptor blockade (tezosentan) was performed in the absence and presence of single or combined inhibition of endothelial NO synthase (eNOS, with N(omega)-nitro-l-arginine) and cyclo-oxygenase (COX, with indometacin). In normal swine, mixed ET(A)/ET(B) blockade decreased pulmonary vascular resistance, but only during exercise. In MI swine, an increased ET-mediated vasoconstrictor influence was observed in the pulmonary circulation both at rest and during exercise. Inhibition of COX resulted in pulmonary vasoconstriction at rest in MI, but not in normal swine; this vasoconstriction in MI swine was normalized by ET(A)/ET(B) receptor blockade. Inhibition of eNOS enhanced the vasodilator response to ET(A)/ET(B) blockade, indicating that NO blunts the pulmonary vasoconstrictor influence of ET. However, this vasodilator response was enhanced to a similar degree in MI and normal swine. In summary, swine with a recent MI are characterized by an exaggerated pulmonary vasoconstrictor influence of ET. This increased ET-mediated pulmonary vasoconstrictor influence is not caused by a loss of NO bioavailability, and is blunted by an increased prostanoid-mediated vasodilatation. In conclusion, an increased ET-mediated vasoconstriction, which does not appear to be the result of loss of endothelial vasodilators, contributes to pulmonary hypertension after MI.
Mesh Headings (Keywords): Animals, Endothelins, Endothelium, Vascular, Female, Hypertension, Pulmonary, Male, Myocardial Infarction, Nitric Oxide, Physical Conditioning, Animal, Prostaglandins, Pulmonary Circulation, Swine, Vasoconstriction, Vasomotor System
Check for Full Text / PubMed Unique Identifier (PMID): 17289783
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.