Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin

被引:217
作者
Ruschitzka, FT
Wenger, RH
Stallmach, T
Quaschning, T
de Wit, C
Wagner, K
Labugger, R
Kelm, M
Noll, G
Rülicke, T
Shaw, S
Lindberg, RLP
Rodenwaldt, B
Lutz, H
Bauer, C
Lüscher, TF
Gassmann, M
机构
[1] Univ Zurich Irchel, Inst Physiol, CH-8057 Zurich, Switzerland
[2] Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland
[3] Univ Zurich Hosp, Cent Biol Lab, CH-8091 Zurich, Switzerland
[4] Univ Munich, Inst Physiol, D-80336 Munich, Germany
[5] Univ Clin Lubeck, Dept Anesthesiol & Physiol, D-23538 Lubeck, Germany
[6] Univ Hosp Dusseldord, Dept Cardiol, D-40225 Dusseldorf, Germany
[7] Univ Hosp Bern, Dept Clin Res, CH-3010 Bern, Switzerland
[8] Univ Basel Hosp, Dept Res & Neurol, CH-4031 Basel, Switzerland
[9] Univ Zurich, Dept Vet Internal Med, CH-8057 Zurich, Switzerland
关键词
D O I
10.1073/pnas.97.21.11609
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 bur 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.
引用
收藏
页码:11609 / 11613
页数:5
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