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Citations to this article

Prolonged endothelin A receptor blockade attenuates chronic pulmonary hypertension in the ovine fetus.
D D Ivy, … , R M Tuder, S H Abman
D D Ivy, … , R M Tuder, S H Abman
Published March 15, 1997
Citation Information: J Clin Invest. 1997;99(6):1179-1186. https://doi.org/10.1172/JCI119274.
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Research Article

Prolonged endothelin A receptor blockade attenuates chronic pulmonary hypertension in the ovine fetus.

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Abstract

Based on past studies of an experimental model of severe intrauterine pulmonary hypertension, we hypothesized that endothelin-1 (ET-1) contributes to high pulmonary vascular resistance (PVR), hypertensive lung structural changes, and right ventricular hypertrophy (RVH) caused by prolonged closure of the ductus arteriosus. To test this hypothesis, we studied the effects of BQ 123, a selective ET(A) receptor antagonist, after ligation of the ductus arteriosus in utero. In 19 late gestation fetal lambs (126+/-3 d; 147 d, term) we ligated the ductus arteriosus at surgery, and treated animals with either BQ 123 (1 mg/d) or vehicle (0.1% DMSO, HTN) in the pulmonary artery for 8 d. Chronic BQ 123 treatment attenuated the rise in mean pulmonary artery pressure (PAP) 8 d after ductus arteriosus ligation (78+/-2, HTN vs. 70+/-4 mmHg, BQ 123, P < 0.05). To study the effects of ET(A) blockade at birth, 15 animals were delivered by cesarean section and ventilated with 10% oxygen (O2), 100% O2 and inhaled nitric oxide (NO). Lambs treated with BQ 123 had lower PVR after delivery during ventilation with 10% O2, 100% O2, and inhaled NO (HTN vs. BQ 123, P < 0.05 for each intervention). Acute BQ 123 treatment (2 mg/30 min) lowered PVR in three HTN animals ventilated with 100% O2 and inhaled NO (P < 0.05). Chronic BQ 123 treatment prevented the development of RVH as determined by the ratio of the right ventricle/left ventricle + septum (0.79+/-0.03, HTN vs. 0.57+/-0.06, BQ 123, P < 0.05) and attenuated the increase in wall thickness of small pulmonary arteries (61+/-2, HTN vs. 50+/-2%, BQ 123, P < 0.05). In summary, chronic intrauterine ET(A) receptor blockade decreased PAP in utero, decreased RVH and distal muscularization of small pulmonary arteries, and increased the fall in PVR at delivery. We conclude that ET(A) receptor stimulation contributes to the pathogenesis and pathophysiology of experimental perinatal pulmonary hypertension.

Authors

D D Ivy, T A Parker, J W Ziegler, H L Galan, J P Kinsella, R M Tuder, S H Abman

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Total citations by year

Year: 2023 2022 2021 2020 2018 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1964 Total
Citations: 1 2 3 3 1 3 1 3 16 5 3 4 2 4 5 4 5 3 5 4 8 8 7 6 1 1 108
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2012 (5)

Title and authors Publication Year
Reactive oxygen and nitrogen species in pulmonary hypertension
DM Tabima, S Frizzell, MT Gladwin
Free radical biology & medicine 2012
The Pulmonary Circulation in Neonatal Respiratory Failure
S Lakshminrusimha
Clinics in Perinatology 2012
Endothelin-1 impairs angiogenesis in vitro through Rho-kinase activation after chronic intrauterine pulmonary hypertension in fetal sheep
J Gien, N Tseng, G Seedorf, G Roe, SH Abman
Pediatric Research 2012
Enhanced central and conduit pulmonary arterial reservoir function offsets reduced ductal systolic outflow during constriction of the fetal ductus arteriosus
JJ Smolich, DJ Penny, JP Mynard
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 2012
Increased right ventricular output and central pulmonary reservoir function support rise in pulmonary blood flow during adenosine infusion in the ovine fetus
JJ Smolich, DJ Penny, JP Mynard
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 2012

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