Angiotensin-converting enzyme inhibition alters nitric oxide and superoxide release in normotensive and hypertensive rats.
Angiotensin-converting enzyme inhibition alters nitric oxide and superoxide release in normotensive and hypertensive rats.
复制标题
血管紧张素转换酶抑制改变血压正常和高血压大鼠中一氧化氮和超氧化物的释放。
DOI：
10.1161/01.hyp.30.5.1183
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Malinski,T
中科院分区：
文献类型：
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作者：
Wiemer,G;Linz,W;Hatrik,S;Schölkens,BA;Malinski,T
≈1月龄雄性正常血压大鼠(n=26)和自发性高血压大鼠(n=38)随机分为3组，分别给予安慰剂、低剂量和高剂量血管紧张素转换酶抑制剂雷米普利(10μg·kg−1·d−1，非降压剂或1 mg·kg−1·d−1，降压剂)。与安慰剂治疗相比，两种剂量的雷米普利分别增加了新鲜切除的颈动脉和胸主动脉内皮结构性一氧化氮合酶的表达(Western印迹)和合成的一氧化氮(卟啉感受器)的合成。矛盾的是，这种活性与24/22月龄正常血压/高血压大鼠新鲜切除的主动脉中超氧化物积累(化学发光)的增加/减少有关。在血压正常的大鼠中，与安慰剂治疗相比，降压药雷米普利治疗后超氧化物歧化酶积累量增加了三倍，这很可能是因为内皮细胞构成的一氧化氮合酶表达增加了300%(其中一些可能是由于局部l-精氨酸或四氢生物蝶呤缺乏引起的)。在高血压大鼠中，与安慰剂治疗相比，长期降压雷米普利治疗使一氧化氮的可获得性增加了35%，这可能有助于保护内皮细胞，并通过抑制超氧化物的产生来防止其功能障碍。一氧化氮产生的增加伴随着超氧化物积累的减少(大约是安慰剂水平的三分之一)与先前报道的使用雷米普利降压剂治疗的遗传性高血压大鼠的寿命延长+40%呈正相关。
Young (≈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 ≈2 years with, respectively, placebo, low doses, or high doses of an angiotensin-converting enzyme inhibitor, ramipril (10 μg · 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 inl-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.