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Titolo:
Developmental changes in endothelin expression and activity in the ovine fetal lung
Autore:
Ivy, DD; Le Cras, TD; Parker, TA; Zenge, JP; Jakkula, M; Markham, NE; Kinsella, JP; Abman, SH;
Indirizzi:
Childrens Hosp, Dept Cardiol, Denver, CO 80218 USA Childrens Hosp Denver CO USA 80218 sp, Dept Cardiol, Denver, CO 80218 USA Univ Colorado, Sch Med, Pediat Heart Lung Ctr, Denver, CO 80218 USA Univ Colorado Denver CO USA 80218 at Heart Lung Ctr, Denver, CO 80218 USA Univ Colorado, Sch Med, Pediat Cardiol Sect, Denver, CO 80218 USA Univ Colorado Denver CO USA 80218 diat Cardiol Sect, Denver, CO 80218 USA Univ Colorado, Sch Med, Sect Pediat Pulm Med, Denver, CO 80218 USA Univ Colorado Denver CO USA 80218 t Pediat Pulm Med, Denver, CO 80218 USA Univ Colorado, Sch Med, Sect Pediat Neonatol, Denver, CO 80218 USA Univ Colorado Denver CO USA 80218 t Pediat Neonatol, Denver, CO 80218 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
fascicolo: 4, volume: 278, anno: 2000,
pagine: L785 - L793
SICI:
1040-0605(200004)278:4<L785:DCIEEA>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
PULMONARY BLOOD-FLOW; DUCTUS-ARTERIOSUS; RECEPTOR BLOCKADE; BIG ENDOTHELIN-1; L-ARGININE; LAMBS; CIRCULATION; FETUS; RESPONSES; VASODILATION;
Keywords:
endothelin receptors; pulmonary hypertension; persistent pulmonary hypertension of the newborn; fetus; pulmonary circulation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Ivy, DD Childrens Hosp, Dept Cardiol, Box B100,1056 E 19th Ave, Denver, CO80218 USA Childrens Hosp Box B100,1056 E 19th Ave Denver CO USA 80218 18 USA
Citazione:
D.D. Ivy et al., "Developmental changes in endothelin expression and activity in the ovine fetal lung", AM J P-LUNG, 278(4), 2000, pp. L785-L793

Abstract

Mechanisms that regulate endothelin (ET) in the perinatal lung are complexand poorly understood, especially with regard to the role of ET before andafter birth. We hypothesized that the ET system is developmentally regulated and that the balance of ETA and ETB receptor activity favors vasoconstriction. To test this hypothesis, we performed a series of molecular and physiological studies in the fetal lamb, newborn lamb, and adult sheep. Lung preproET-1 mRNA levels, tissue ET peptide levels, and cellular localization of ET-1 expression were determined by Northern blot analysis, peptide assay,and immunohistochemistry in distal lung tissue from fetal lambs between 70and 140 days (term = 145 days), newborn lambs, and ewes. Lung mRNA expression for the ETA and ETB receptors was also measured at these ages. We foundthat preproET-1 mRNA expression increased from 113 to 130 days gestation. Whole lung ET protein content was highest at 130 days gestation but decreased before birth in the fetal lamb lung. Immunolocalization of ET-1 protein showed expression of ET-1 in the vasculature and bronchial epithelium at all gestational ages. ETA receptor mRNA expression and ETB receptor mRNA increased from 90 to 125 and 135 days gestation. To determine changes in activity of the ETA and ETB receptors, we studied the effect of selective antagonists to the ETA or ETB receptors at 120, 130, and 140 days of fetal gestation. ETA receptor-mediated vasoconstriction increased from 120 to 140 days, whereas blockade of the ETB receptor did not change basal fetal pulmonary vascular tone at any age examined. We conclude that the ET system is developmentally regulated and that the increase in ETA receptor gene expression correlates with the onset of the vasodilator response to ETA receptor blockade. Although ETB receptor gene expression increases during late gestation, the balance of ET receptor activity favors vasoconstriction under basal conditions. We speculate that changes in ET receptor activity play important roles in regulation of pulmonary vascular tone in the ovine fetus.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 16:48:50