Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: Involvement of the renin-angiotensin system
Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: Involvement of the renin-angiotensin system
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DOI：
10.1291/hypres.29.813
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发表时间：
2006-10-01
影响因子：
5.4
通讯作者：
Iida, Mitsuo
中科院分区：
文献类型：
--
作者：
Akasaki, Takashi;Ohya, Yusuke;Iida, Mitsuo
尽管血管细胞表达烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）氧化酶Nox家族的多个成员，包括gp91phox、Nox1和Nox4，但这些成员在慢性高血压血管损伤中的不同表达原因和具体作用尚不清楚。因此，我们通过实时聚合酶链反应定量测定了这些NAD(P)H氧化酶组分的mRNA表达，并评估了32周龄卒中易发自发性高血压大鼠（SHRSP）和年龄匹配的Wistar Kyoto大鼠（WKY）主动脉中超氧化物的产生和形态变化。与WKY相比，SHRSP的主动脉介质中Nox4 mRNA水平高出约2.5倍，Nox1 mRNA水平高出约10倍。gp91phox和p22phox mRNA在SHRSP和WKY中的表达具有可比性。从24周龄开始，用高剂量或低剂量坎地沙坦（4mg /kg/天或0.2 mg/kg/天），或肼嗪（30mg /kg/天）和氢氯噻嗪（4.5 mg/kg/天）联合治疗SHRSP，持续8周。高剂量坎地沙坦或肼嗪联合氢氯噻嗪可使SHRSP血压降至WKY血压水平，而低剂量坎地沙坦无明显降压作用。高剂量坎地沙坦几乎使中度增厚和纤维化以及SHRSP中超氧化物产生的增加正常化，并用低剂量坎地沙坦或肼嗪加氢氯噻嗪部分纠正。降压治疗引起的这些变化与Nox4和Nox1 mRNA表达的下降相一致。这些结果表明，血压和血管紧张素II型1受体激活参与了Nox1和Nox4表达的上调，并可能参与慢性高血压血管损伤。
Although vascular cells express multiple members of the Nox family of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, including gp91phox, Nox1, and Nox4, the reasons for the different expressions and specific roles of these members in vascular injury in chronic hypertension have remained unclear. Thus, we quantified the mRNA expressions of these NAD(P)H oxidase components by real-time polymerase chain reaction and evaluated superoxide production and morphological changes in the aortas of 32-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar Kyoto rats (WKY). The aortic media of SHRSP had an approximately 2.5-fold greater level of Nox4 mRNA and an approximately 10-fold greater level of Nox1 mRNA than WKY. The mRNA expressions of gp91phox and p22phox in SHRSP and WKY were comparable. SHRSP were treated from 24 weeks of age for 8 weeks with either high or low doses of candesartan (4 mg/kg/day or 0.2 mg/kg/day), or a combination of hydralazine (30 mg/kg/day) and hydrochlorothiazide (4.5 mg/kg/day). The high-dose candesartan or the hydralazine plus hydrochlorothiazide decreased the blood pressure of SHRSP to that of WKY, whereas the low-dose candesartan exerted no significant antihypertensive action. Media thickening and fibrosis, as well as the increased production of superoxide in SHRSP, were nearly normalized with high-dose candesartan and partially corrected with low-dose candesartan or hydralazine plus hydrochlorothiazide. These changes by antihypertensive treatment paralleled the decrease in mRNA expression of Nox4 and Nox1. These results suggest that blood pressure and angiotensin II type 1 receptor activation are involved in the up-regulation of Nox1 and Nox4 expression, which could contribute to vascular injury during chronic hypertension.