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Prolonged endothelin B receptor blockade causes pulmonary hypertension in the ovine fetus.
Ivy, D D; Parker, T A; Abman, S H.
Afiliación
  • Ivy DD; Section of Cardiology, Pediatric Heart Lung Center, University of Colorado School of Medicine, and The Children's Hospital, Denver, Colorado 80218, USA. dunbar.ivy@UCHSC.edu
Am J Physiol Lung Cell Mol Physiol ; 279(4): L758-65, 2000 Oct.
Article en En | MEDLINE | ID: mdl-11000137
Endothelin (ET)-1 contributes to regulation of pulmonary vascular tone and structure in the normal ovine fetus and in models of perinatal pulmonary hypertension. The hemodynamic effects of ET-1 are due to activation of its receptors. The ET(A) receptor mediates vasoconstriction and smooth muscle cell proliferation, whereas the ET(B) receptor mediates vasodilation. In a lamb model of chronic intrauterine pulmonary hypertension, ET(B) receptor activity and gene expression are decreased. To determine whether prolonged ET(B) receptor blockade causes pulmonary hypertension, we studied the hemodynamic effects of selective ET(B) receptor blockade with BQ-788. Animals were treated with an infusion of either BQ-788 or vehicle for 7 days. Prolonged BQ-788 treatment increased pulmonary arterial pressure and pulmonary vascular resistance (P < 0.05). The pulmonary vasodilator response to sarafotoxin 6c, a selective ET(B) receptor agonist, was attenuated after 7 days of BQ-788 treatment, demonstrating pharmacological blockade of the ET(B) receptor. Animals treated with BQ-788 had greater right ventricular hypertrophy and muscularization of small pulmonary arteries (P < 0. 05). Lung ET-1 levels were threefold higher in the animals treated with BQ-788 (P < 0.05). We conclude that prolonged selective ET(B) receptor blockade causes severe pulmonary hypertension and pulmonary vascular remodeling in the late-gestation ovine fetus.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligopéptidos / Piperidinas / Receptores de Endotelina / Endotelina-1 / Hemodinámica / Hipertensión Pulmonar Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Pregnancy Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2000 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligopéptidos / Piperidinas / Receptores de Endotelina / Endotelina-1 / Hemodinámica / Hipertensión Pulmonar Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Pregnancy Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2000 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos