PMID: 8594905Dec 1, 1995Paper

Endothelin-1 vasoactive responses in lambs with pulmonary hypertension and increased pulmonary blood flow

The American Journal of Physiology
J WongJeffrey R Fineman

Abstract

Increased concentrations of endothelin-1 (ET-1) are found in children with congenital heart diseases that produce increased pulmonary blood flow and pulmonary hypertension, but the role of ET-1 in the pathophysiology of pulmonary hypertension is unclear. Therefore, we investigated ET-1-induced vasoactive responses and ET-1 concentrations in an animal model of pulmonary hypertension and increased pulmonary blood flow. Vascular shunts were placed between the ascending aorta and main pulmonary artery in seven late-gestation fetal sheep. Four weeks after spontaneous delivery, ET-1 increased pulmonary vascular resistance by 29.7 +/- 34.4% (P < 0.05), the ETb-receptor agonist [Ala1,3,11,15]ET-1 (4AlaET-1) had no effect, and the ETa-receptor antagonist cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp) (BQ-123) decreased pulmonary vascular resistance by -16.0 +/- 5.6% (P < 0.05). In contrast, in six control lambs with a similar degree of pulmonary hypertension induced by U-46619, ET-1 and 4AlaET-1 decreased pulmonary vascular resistance by 24.8 +/- 17.6, and 20.0 +/- 13.8%, respectively (P < 0.05). In addition, systemic arterial concentrations of immunoreactive ET-1 were elevated in lambs with pulmonary hypertension (29.2 +/- 9.6 vs. 15.2 +/- 10.7 ...Continue Reading

Citations

Nov 24, 1999·Artificial Organs·R H Steinhorn, J R Fineman
Apr 24, 2010·American Journal of Respiratory and Critical Care Medicine·Roberta L KellerJeffrey R Fineman
May 25, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sohrab FratzJeffrey R Fineman
Sep 7, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Gregory A RossJeffrey R Fineman
Nov 1, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Peter OishiJeffrey R Fineman
Feb 18, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Sanjeev A DatarJeffrey R Fineman
Oct 26, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Boaz OvadiaJeffrey R Fineman

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