Expression of NAD(P)H oxidase subunits and their contribution to cardiovascular damage in aldosterone/salt-induced hypertensive rat.

Expression of NAD(P)H oxidase subunits and their contribution to cardiovascular damage in aldosterone/salt-induced hypertensive rat.
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DOI:
10.3346/jkms.2008.23.6.1039
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发表时间:
2008-12
影响因子:
4.5
通讯作者:
Park, Jeong Bae
Park, Jeong Bae
中科院分区:
医学4区
文献类型:
--
作者:
Park, Young Mee;Lim, Bong Hee;Touyz, Rhian M.;Park, Jeong Bae

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NAD(P)H氧化酶在醛固酮-盐大鼠高血压及其并发症中起重要作用。我们质疑NAD(P)H氧化酶亚单位的表达和活性是否受醛固酮调节,以及这是否与靶器官损伤有关。大鼠输注醛固酮(0.75 µg/hr/d)6周,并给予0.9% NaCl±氯沙坦(30 mg/kg/d)、螺内酯(200 mg/kg/d)和夹竹桃苷(1.5 mM/L)。安体舒通可完全预防醛固酮盐性高血压,氯沙坦和夹竹桃素可适度预防醛固酮盐性高血压。醛固酮使主动脉NAD(P)H氧化酶活性增加34%,螺内酯和氯沙坦抑制该活性。在注射醛固酮的大鼠中,主动脉亚基p47 phox、gp 91 phox和p22 phox的表达分别增加了5.5倍、4.7倍和3.2倍,而安体舒通完全降低了这一表达,而洛沙坦和夹竹桃麻素则部分降低了这一表达。因此,NAD(P)H氧化酶表达的增加可能通过增加各亚基的表达而促进醛固酮盐性高血压的心血管损害。
NAD(P)H oxidase plays an important role in hypertension and its complication in aldosterone-salt rat. We questioned whether NAD(P)H oxidase subunit expression and activity are modulated by aldosterone and whether this is associated with target-organ damage. Rats were infused with aldosterone (0.75 µg/hr/day) for 6 weeks and were given 0.9% NaCl±losartan (30 mg/kg/day), spironolactone (200 mg/kg/day), and apocynin (1.5 mM/L). Aldosterone-salt hypertension was prevented completely by spironolactone and modestly by losartan and apocynin. Aldosterone increased aortic NAD(P)H oxidase activity by 34% and spironolactone and losartan inhibited the activity. Aortic expression of the subunits p47phox, gp91phox, and p22phox increased in aldosterone-infused rats by 5.5, 4.7, and 3.2-fold, respectively, which was decreased completely by spironolactone and partially by losartan and apocynin. Therefore, the increased expression of NAD(P)H oxidase may contribute to cardiovascular damage in aldosterone-salt hypertension through the increased expression of each subunit.
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