Angiotensin II type 1 receptor blocker prevents atrial structural remodeling in rats with hypertension induced by chronic nitric oxide inhibition
Angiotensin II type 1 receptor blocker prevents atrial structural remodeling in rats with hypertension induced by chronic nitric oxide inhibition
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DOI：
10.1291/hypres.29.277
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发表时间：
2006-04-01
影响因子：
5.4
通讯作者：
Kitakaze, Masafumi
中科院分区：
文献类型：
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作者：
Okazaki, Hidetoshi;Minamino, Tetsuo;Kitakaze, Masafumi
高血压患者心房颤动（AF）的患病率增加。血管紧张素 11 参与结构性心房重塑，这有助于起搏动物模型中 AF 的发生和维持。我们研究了血管紧张素 11 在高血压大鼠心房结构重塑中的作用。 10周龄雄性Wistar-Kyoto大鼠被随机分为4组：对照组（不处理）、N-omega-硝基-L-精氨酸甲酯（L-NAME）组（在饮用水中给予一氧化氮合酶抑制剂L-NAME 1 g/l）、L-NAME+坎地沙坦组（L-NAME加坎地沙坦-血管紧张素II受体阻滞剂（ARB）-0.1） mg/kg/天），以及 L-NAME + 肼屈嗪组（L-NAME 加肼屈嗪，饮用水中浓度为 120 mg/l）。治疗八周后，L-NAME 组的收缩压显着高于对照组（197 +/- 12 vs.138 +/- 5 mmHg，p < 0.05）。坎地沙坦或肼屈嗪联合 L-NAME 可将收缩压降低至基线。长期抑制NO合成会增加心房组织中纤维化的程度和转化生长因子-β的表达，坎地沙坦可以阻止这两种作用，但肼屈嗪则不能。 L-NAME 组诱发了心脏肥大和功能障碍，坎地沙坦也可以预防这些影响，但肼苯哒嗪则不能。相反，坎地沙坦和肼苯达嗪可恢复高血压大鼠心房内膜中血栓调节蛋白表达的降低。在长期抑制 NO 合成而诱发的高血压大鼠的心脏中，ARB 可以防止心房结构重塑，而心房结构重塑可能是导致 AF 发生的因素。
The prevalence of atrial fibrillation (AF) increases in patients with hypertension. Angiotensin 11 is involved in structural atrial remodeling, which contributes to the onset and maintenance of AF in paced animal models. We investigated the role of angiotensin 11 in atrial structural remodeling in rats with hypertension. Ten-week-old male Wistar-Kyoto rats were randomly divided into 4 groups: a control group (no treatment), an N-omega-nitro-L-arginine methyl ester (L-NAME) group (administered L-NAME, an inhibitor of nitric oxide synthase, 1 g/l in drinking water), an L-NAME+candesartan group (L-NAME plus candesartan-an angiotensin II receptor blocker (ARB)-at 0.1 mg/kg/day), and an L-NAME + hydralazine group (L-NAME plus hydralazine at 120 mg/l in drinking water). Eight weeks after treatment, the L-NAME group showed significantly higher systolic blood pressure than the control group (197 +/- 12 vs.138 +/- 5 mmHg, p < 0.05). Candesartan or hydralazine with L-NAME reduced systolic blood pressure to baseline. Chronic inhibition of NO synthesis increased the extent of fibrosis and transforming growth factor-beta expression in atrial tissue, and both of these effects were prevented by candesartan, but not by hydralazine. Cardiac hypertrophy and dysfunction were induced in the L-NAME group, and these effects were also prevented by candesartan, but not by hydralazine. In contrast, the decrease in thrombomodulin expression in the atrial endocardium in hypertensive rats was restored by candesartan and hydralazine. The ARB prevented atrial structural remodeling, a possible contributing factor for the development of AF, in the hearts of rats with hypertension induced by long-term inhibition of NO synthesis.