ANG II stimulates endothelial nitric oxide synthase expression in bovine pulmonary artery endothelium

被引:41
作者
Olson, SC
Dowds, TA
Pino, PA
Barry, MT
BurkeWolin, T
机构
[1] NEW YORK MED COLL, DEPT PHARMACOL, VALHALLA, NY 10595 USA
[2] NEW YORK MED COLL, DEPT BIOCHEM, VALHALLA, NY 10595 USA
[3] NEW YORK MED COLL, DEPT MED, VALHALLA, NY 10595 USA
关键词
angiotensin II; pulmonary circulation; hypertension;
D O I
10.1152/ajplung.1997.273.2.L315
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Although angiotensin II (ANG II) is a known pulmonary vasoconstrictor, the purpose of this study was to examine the effect of ANG II on pulmonary artery endothelial cell nitric oxide synthase (ecNOS) mRNA and protein expression. Cultured bovine pulmonary artery endothelial (BPAE; passages 5-8) cells were incubated for 0-12 h with 10(-6) M ANG II. Total RNA was extracted, and ecNOS expression was assessed by Northern blot analysis. In BPAE cells, ecNOS mRNA was significantly increased 2.4 +/- 0.3-fold (P < 0.05 vs. basal; n = 5) 6 h after the addition of ANG II over basal levels. In a similar time course, it was found that ecNOS protein concentrations are increased 247 +/- 62% (P < 0.05 vs. basal; n = 8) over basal levels 4 h after ANG II addition. There is a second protein peak 8 h after ANG II addition in which ecNOS was increased 333 +/- 145% over basal (P < 0.05, n = 3). These data suggest that ANG II stimulates ecNOS mRNA expression and are followed by increased levels of ecNOS protein in cultured BPAE cells, consistent with an observed increase in nitrite production. Both the increase in ecNOS protein and mRNA expression could be inhibited with the ANG II receptor antagonist saralasin. Additionally, actinomycin D, an inhibitor of transcription, prevented the rise in mRNA at 6 h while cycloheximide inhibited the initial protein peak. The effects of ANG II on ecNOS were specific for the pulmonary artery endothelium. Addition of ANG II did not increase ecNOS protein or mRNA expression in parallel studies in bovine coronary artery endothelium. The stimulation of ecNOS by ANG II may act to protect the lung and maintain low pulmonary artery pressures in the renin-agiotensin model of systemic hypertension.
引用
收藏
页码:L315 / L321
页数:7
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