Intrauterine growth retardation is associated with reduced activity and expression of the cationic amino acid transport systems y(+)/hCAT-1 and y(+)/hCAT-2B and lower activity of nitric oxide synthase in human umbilical vein endothelial cells

Casanello, P; Sobrevia L.

Abstract

Intrauterine growth retardation (IUGR) is associated with vascular complications leading to hypoxia and abnormal fetal development. The effect of IUGR on L-arginine transport and nitric oxide (NO) synthesis was investigated in cultures of human umbilical vein endothelial cells (HUVECs). IUGR was associated with membrane depolarization and reduced L-arginine transport (Vmax=5.8±0.2 versus 3.3±0.1 pmol/?g protein per minute), with no significant changes in transport affinity (Km=159±15 versus 137±14 ?mol/L). L-Arginine transport was trans-stimulated (8- to 9-fold) in cells from normal and IUGR pregnancies. IUGR was associated with reduced production of L-[3H]citrulline from L-[3H]arginine, lower nitrite and intracellular L-arginine, L-citrulline, and cGMP. IUGR decreased hCAT-1 and hCAT-2B mRNA, and increased eNOS mRNA and protein levels. IUGR-associated inhibition of L-arginine transport and NO synthesis, and membrane depolarization were reversed by the NO donor S-nitroso-N-acetyl-L,D-penicillamine. In summary, endothelium from fetuses with IUGR exhibit altered L-arginine transport and NO synthesis (L-arginine/NO pathway), reduced expression and activity of hCAT-1 and hCAT-2B and reduced eNOS activity. Alterations in L-arginine/NO pathway could be critical for the physiological processes involved in the etiology of IUGR in human pregnancies.

Más información

Título según WOS: Intrauterine growth retardation is associated with reduced activity and expression of the cationic amino acid transport systems y(+)/hCAT-1 and y(+)/hCAT-2B and lower activity of nitric oxide synthase in human umbilical vein endothelial cells
Título según SCOPUS: Intrauterine growth retardation is associated with reduced activity and expression of the cationic amino acid transport systems y+/hCAT-1 and y+/hCAT-2B and lower activity of nitric oxide synthase in human umbilical vein endothelial cells
Título de la Revista: CIRCULATION RESEARCH
Volumen: 91
Número: 2
Editorial: LIPPINCOTT WILLIAMS & WILKINS
Fecha de publicación: 2002
Página de inicio: 127
Página final: 134
Idioma: English
URL: http://circres.ahajournals.org/cgi/doi/10.1161/01.RES.0000027813.55750.E7
DOI:

10.1161/01.RES.0000027813.55750.E7

Notas: ISI, SCOPUS