In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 21 ( 2000-10-10), p. 11609-11613
Abstract:
Nitric oxide (NO) induces vasodilatatory, antiaggregatory, and
antiproliferative effects in vitro . To delineate
potential beneficial effects of NO in preventing vascular disease in vivo , we generated transgenic mice overexpressing
human erythropoietin. These animals induce polyglobulia known to be associated with a high incidence of vascular disease. Despite
hematocrit levels of 80%, adult transgenic mice did not develop hypertension or thromboembolism. Endothelial NO synthase levels,
NO-mediated endothelium-dependent relaxation and circulating and vascular tissue NO levels were markedly increased. Administration of
the NO synthase inhibitor N G -nitro-L-arginine methyl
ester (L-NAME) led to vasoconstriction of peripheral resistance vessels, hypertension, and death of transgenic mice, whereas wild-type
siblings developed hypertension but did not show increased mortality. L-NAME-treated polyglobulic mice revealed acute left ventricular
dilatation and vascular engorgement associated with pulmonary congestion and hemorrhage. In conclusion, we here unequivocally
demonstrate that endothelial NO maintains normotension, prevents cardiovascular dysfunction, and critically determines survival in vivo under conditions of increased hematocrit.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.97.21.11609
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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