Angiotensin-converting enzyme inhibition alters nitric oxide and superoxide release in normotensive and hypertensive rats

被引:74
作者
Wiemer, G
Linz, W
Hatrik, S
Scholkens, BA
Malinski, T
机构
[1] OAKLAND UNIV, INST BIOTECHNOL, DEPT CHEM, ROCHESTER, MI 48309 USA
[2] HOECHST MARION ROUSSEL, DG RES CARDIOVASC, FRANKFURT, GERMANY
关键词
ramipril; nitric oxide; nitric oxide synthase-III; hypertension; aging; endothelium; superoxide;
D O I
10.1161/01.HYP.30.5.1183
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Young (approximate to 1 month old) male normotensive Wistar-Kyoto rats (n=26) and spontaneously hypertensive rats (n=38) were randomized into three groups treated via drinking water for approximate to 2 years with, respectively, placebo, low doses, or high doses of an angiotensin-converting enzyme inhibitor, ramipril(10 mu g.kg(-1).d(-1), non-blood pressure-lowering dose, or 1 mg.kg(-1).d(-1), blood pressure-lowering dose). Relative to placebo treatment in each respective rat strain, both ramipril dosages increased endothelial constitutive nitric oxide synthase expression (Western blot) and resultant synthesis of nitric oxide (porphyrinic sensor) in freshly excised carotids and thoracic aortas, respectively. Paradoxically, this activity was associated with an increased/decreased superoxide accumulation (chemiluminescence) in freshly excised aortas from 24-/22-month-old normotensive/hypertensive rats. In normotensive rats, relative to placebo treatment, the threefold increase in superoxide accumulation with antihypertensive ramipril treatment is most likely from the >300% increase in endothelial constitutive nitric oxide synthase expression (some of which may be disarranged by local insufficiencies in L-arginine or tetrahydrobiopterin). In hypertensive rats, relative to placebo treatment, the 35% increase in nitric oxide availability by long-term antihypertensive ramipril treatment may contribute to the preservation of the endothelium and prevent its dysfunction by inhibiting superoxide production. Increased nitric oxide production with concomitant decreased superoxide accumulation (approximately one third of placebo levels) correlates positively with the previously reported +40% life span extension for rats with genetic hypertension that were treated with antihypertensive doses of ramipril.
引用
收藏
页码:1183 / 1190
页数:8
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