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Exogenous, basal, and flow‐induced nitric oxide production and endothelial cell proliferation
Author(s) -
Gooch Keith J.,
Dangler Charles A.,
Frangos John A.
Publication year - 1997
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199706)171:3<252::aid-jcp3>3.0.co;2-n
Subject(s) - umbilical vein , cell growth , endothelial stem cell , nitric oxide , endothelium , nitric oxide synthase , biology , endogeny , autocrine signalling , microbiology and biotechnology , chemistry , cell culture , medicine , biochemistry , endocrinology , in vitro , genetics
The role of nitric oxide (NO) from endogenous and exogenous sources in regulating large vessel and microvascular endothelial cell proliferation was investigated. Exogenous NO liberated from five different chemical donors inhibited bovine aortic, bovine retinal microvascular, and human umbilical vein endothelial cell proliferation in a dose‐dependent manner as determined by 3 H‐thymidine incorporation. The potency of the donors varied as a function of the donors' half‐lives. Donors with half‐lives greater than 30 min were more effective than donors with significantly shorter half‐lives. Coincubation of endothelial cells with 0.4 mM deoxyadenosine and 0.4 mM deoxyguanosine reduced the percentage of inhibition due to an NO donor. These data are consistent with a ribonucleotide reductase‐dependent mechanism of inhibition. Inhibition of basal NO production with four different inhibitors of nitric oxide synthase (NOS) did not modify proliferation. Laminar flow with a wall shear stress of 22 dyn/cm 2 inhibited the proliferation of subconfluent bovine aortic endothelial cells. The addition of a NOS inhibitor did not abrogate the flow‐induced inhibition of proliferation, suggesting that flow‐stimulated release of NO from endothelial cells did not account for flow‐induced inhibition of proliferation. Taken together, these data suggest that relatively large concentrations of exogenous NO inhibit endothelial cell proliferation, while endogenous levels of NO are inadequate to inhibit proliferation. J. Cell. Physiol. 171:252–258, 1997. © 1997 Wiley‐Liss, Inc.