Role of nitric oxide in the autocrine control of growth and
apoptosis of endothelial cells.
L[acute]opez-Farr[acute]e, Antonio, Lourdes S[acute]anchez De Miguel,
Carlos Caramelo, Juana G[acute]omez-Mac[acute]ias, Rosa
Garc[acute]ia, Juan Ram[acute]on Mosquera, Trinidad De Frutos,
Inmaculada Mill[acute]as, Francisca Rivas, Gemma Echezarreta, Santos
Casado.
Laboratorio de Nefrolog[acute]ia-Hipertensi[acute]on. Instituto de
Investigaciones M[acute]edicas. Fundaci[acute]on Jim[acute]enez
D[acute]iaz. Universidad Aut[acute]onoma. Madrid. Spain
APStracts 3:0334H, 1996.
Nitric oxide (NO) is a growth inhibitor for diverse cellular types. In
the present study, we have found that the inhibition of nitric oxide
production in bovine endothelial cells by a L-arginine competitive
antagonist, induces DNA replication, promotes the transition from
prereplicative to replicative phases of the endothelial cell cycle
and an increase in c-myc and c-fos oncogen encoded-proteins
expression. The inhibition of NO generation had, however, a markedly
different outcome depending on the state of confluence of the cells,
namely, proliferation was found in subconfluent cells, whereas
apoptosis occurred in confluent cells. Moreover, Western blot
analysis revealed differences in the constitutive NO synthase
expression in proliferating compared with growth-arrested cells. In
conclusion, these results disclose an alternative mechanism of
endothelial cell apoptosis at the confluent state, which is related
to NO inhibition. Moreover, the fact that the apoptotic phenomenon
occurred in the presence of growth factors indicates the existence of
apoptotic mechanisms which do not require growth factor deprivation.
Received 29 January 1996; accepted in final form 2 August 1996.
APS Manuscript Number H82-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996