Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 282, Issue 3, Pages H862-H871Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00417.2001
Keywords
ductus arteriosus; pulmonary circulation
Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL060190, R01HL061284] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL-61284, HL-60190] Funding Source: Medline
- NICHD NIH HHS [HD-398110] Funding Source: Medline
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Acute partial compression of the fetal ductus arteriosus (DA) results in an initial increase in pulmonary blood flow (PBF) that is followed by acute vasoconstriction. The objective of the present study was to determine the role of nitric oxide (NO)-endothelin-1 (ET-1) interactions in the acute changes in pulmonary vascular tone after in utero partial constriction of the DA. Twelve late-gestation fetal lambs (132-140 days) were instrumented to measure vascular pressures and left PBF. After a 24-h recovery period, acute constriction of the DA was performed by partially inflating a vascular occluder, and the hemodynamic variables were observed for 4 h. In control lambs (n = 7), acute ductal constriction initially increased PBF by 627% (P < 0.05). However, this was followed by active vasoconstriction, such that PBF was restored to preconstriction values by 4 h. This was associated with a 43% decrease in total NO synthase (NOS) activity (P < 0.05) and a 106% increase in plasma ET-1 levels (P < 0.05). Western blot analysis demonstrated no changes in lung tissue endothelial NOS, pre-proET-1, endothelin-converting enzyme-1, or ETB receptor protein levels. The infusion of PD-156707 (an ETA receptor antagonist, n = 5) completely blocked the vasoconstriction and preserved NOS activity. These data suggest that the fetal pulmonary vasoconstriction after acute constriction of the DA is mediated by NO-ET-1 interactions. These include an increase in ETA receptor-mediated vasoconstriction and an ETA receptor-mediated decrease in NOS activity. The mechanisms of these NO-ET-1 interactions, and their role in mediating acute changes in PBF, warrant further studies.
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