p47(phox) is required for afferent arteriolar contractile responses to angiotensin II and perfusion pressure in mice.
p47(phox) is required for afferent arteriolar contractile responses to angiotensin II and perfusion pressure in mice.
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DOI：
10.1161/hypertensionaha.111.184291
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发表时间：
2012-02
期刊：
影响因子：
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通讯作者：
Wilcox CS
中科院分区：
文献类型：
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作者：
Lai EY;Solis G;Luo Z;Carlstrom M;Sandberg K;Holland S;Wellstein A;Welch WJ;Wilcox CS
传入小动脉的肌源性和血管紧张素收缩产生活性氧。耐药血管表达NOX-2和-4。血管紧张素II激活p47 phox/NOX-2，而它下调NOX-4。因此，我们测试的假设，p47 phox增强传入小动脉血管紧张素收缩。p47 phox +/+小鼠输注血管紧张素II可增加肾皮质烟酰胺腺嘌呤二核苷酸磷酸氧化酶活性，而p47 phox-/-小鼠则不然（7±1至12±1; P<0.01 vs 5±1至7±1; NS，103 · RLU · min-1 · μg蛋白质-1），平均动脉压（77±2 ~ 91±2; P<0.005 vs 74±2 ~ 77±1; NS，mmHg）和肾血管阻力（7.5±0.4 ~ 10.1±0.7; P<0.01 vs 7.9±0.4 ~ 8.3±0.4 NS，mmHg/ml·min-1·gkwt-1）。p47 phox-/-小鼠的输入小动脉对10- 6 M血管紧张素II的肌源性反应较低（3.1±0.4 vs 1.4±0.2 dynes·cm-1·mmHg-1; P<0.02），收缩较低（P<0.05）（直径变化+/+：9.3±0.2至3.4±0.6 μm vs -/-：9.9±0.6至7.5±0.4 μm）。血管紧张素和灌注压升高使p47 phox +/+微动脉产生的活性氧显著多于-/-微动脉（P<0.05）。血管紧张素II输注增加了p47 phox +/+小鼠传入小动脉对10-6 M血管紧张素II的最大反应性，但降低了p47 phox-/-小鼠的反应性。血管紧张素输注仅在p47 phox +/+小鼠中增加对血管紧张素II的敏感性。我们的结论是，p47 phox需要增强肾烟酰胺腺嘌呤二核苷酸磷酸氧化酶的活性和基础传入小动脉肌源性和血管紧张素II收缩和切换传入小动脉快速耐受致敏血管紧张素在长期的血管紧张素输注。这些效应可能导致血管紧张素II输注期间的高血压和肾血管收缩。
Myogenic and angiotensin contractions of afferent arterioles generate reactive oxygen species. Resistance vessels express NOX-2 and -4. Angiotensin II activates p47phox/NOX-2 whereas it downregulates NOX-4. Therefore, we tested the hypothesis that p47phox enhances afferent arteriolar angiotensin contractions. Angiotensin II infusion in p47phox +/+, but not -/- mice, increased renal cortical nicotinamide adenine dinucleotide phosphate oxidase activity (7±1 to 12±1; P<0.01 vs 5±1 to 7±1; NS, 103 · RLU · min-1 · μg protein-1), mean arterial pressure (77±2 to 91±2; P<0.005 vs 74±2 to 77±1; NS, mmHg) and renal vascular resistance (7.5±0.4 to 10.1±0.7; P<0.01 vs 7.9±0.4 to 8.3±0.4 NS, mmHg/ml·min-1·gkwt-1). Afferent arterioles from p47phox -/- mice had a lesser myogenic response (3.1±0.4 vs 1.4±0.2 dynes·cm-1·mmHg-1; P<0.02) and a lesser (P<0.05) contraction to 10-6M angiotensin II (diameter change +/+: 9.3±0.2 to 3.4±0.6 μm vs -/-: 9.9±0.6 to 7.5±0.4 μm). Angiotensin and increased perfusion pressure generated significantly (P<0.05) more reactive oxygen species in p47phox +/+ than -/- arterioles. Angiotensin II infusion increased the maximum responsiveness of afferent arterioles from p47phox +/+ mice to 10-6 M angiotensin II yet decreased the response in p47phox -/- mice. The angiotensin infusion increased the sensitivity to angiotensin II only in p47phox +/+ mice. We conclude that p47phox is required to enhance renal nicotinamide adenine dinucleotide phosphate oxidase activity and basal afferent arteriolar myogenic and angiotensin II contractions and to switch afferent arteriolar tachyphylaxis to sensitization to angiotensin during a prolonged angiotensin infusion. These effects likely contribute to hypertension and renal vasoconstriction during infusion of angiotensin II.