Erdös Benedek, Broxson Christopher S, King Michael A, Scarpace Philip J, Tümer Nihal
Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida, USA.
J Hypertens. 2006 Jan;24(1):109-16. doi: 10.1097/01.hjh.0000198026.99600.59.
Centrally applied angiotensin II (Ang II) increases sympathetic nervous activity and mean arterial blood pressure (MAP), but the mediation of these effects is not fully understood.
To test the hypothesis that central effects of Ang II are mediated by reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H]-oxidase-dependent production of superoxide in the hypothalamus.
Under isoflurane anesthesia, male Sprague-Dawley rats were given an intracerebroventricular infusion of either artificial cerebrospinal fluid or apocynin (4 microg/kg per min), a selective inhibitor for NAD(P)H oxidase, for 30 min, followed by Ang II (20 ng) or carbachol (200 ng), while MAP and heart rate were measured at the femoral artery. At the end of the experiments, hydroethidine, a superoxide-sensitive fluorescent dye, was infused intravenously for 10 min, and superoxide production was assessed in the vasoregulatory hypothalamic nuclei using confocal microscopy.
Ang II elicited a rapid 11 +/- 2-mmHg increase in MAP and a 16 +/- 2-beats/min decrease in heart rate. Apocynin abolished these effects of Ang II in a specific manner, as carbachol-induced increases in MAP were unaffected by the inhibition of NAD(P)H oxidase (MAP increased by 9 +/- 2 and 8 +/- 1 mmHg in the absence and presence of apocynin, respectively). In response to Ang II, apocynin-sensitive production of superoxide increased significantly in the nuclei of the anterior hypothalamus, in the subfornical organ, and in the paraventricular nucleus of the hypothalamus.
These findings demonstrate that acute pressor responses of central Ang II are mediated by NAD(P)H-oxidase-dependent production of superoxide in the hypothalamus.
中枢应用血管紧张素II（Ang II）可增加交感神经活动和平均动脉血压（MAP），但其介导这些效应的机制尚未完全明确。
检验Ang II的中枢效应是通过下丘脑烟酰胺腺嘌呤二核苷酸磷酸[NAD(P)H]氧化酶依赖性超氧化物生成减少来介导的这一假说。
在异氟烷麻醉下，给雄性Sprague-Dawley大鼠脑室内输注人工脑脊液或阿朴吗啡（4微克/千克每分钟），阿朴吗啡是NAD(P)H氧化酶的选择性抑制剂，持续30分钟，随后输注Ang II（20纳克）或卡巴胆碱（200纳克），同时在股动脉测量MAP和心率。实验结束时，静脉输注超氧化物敏感荧光染料氢化乙锭10分钟，并用共聚焦显微镜评估血管调节性下丘脑核中的超氧化物生成。
Ang II使MAP迅速升高11±2毫米汞柱，心率降低16±2次/分钟。阿朴吗啡以特异性方式消除了Ang II的这些效应，因为卡巴胆碱诱导的MAP升高不受NAD(P)H氧化酶抑制的影响（在不存在和存在阿朴吗啡时，MAP分别升高9±2和8±1毫米汞柱）。对Ang II的反应中，阿朴吗啡敏感的超氧化物生成在前下丘脑核、穹窿下器官和下丘脑室旁核中显著增加。
这些发现表明，中枢Ang II的急性升压反应是由下丘脑NAD(P)H氧化酶依赖性超氧化物生成介导的。
