Laboratory of Applied Physiology, Veterinary Sciences Department, Center for Agrarian Sciences, Federal University of Paraíba, Areia, PB, Brazil.
Auton Neurosci. 2011 Jan 20;159(1-2):38-44. doi: 10.1016/j.autneu.2010.07.025. Epub 2010 Aug 16.
In some pathological conditions such as hypertension, there is an impairment in the autonomic control of blood pressure resulting in changes in baroreflex sensitivity. In the present study we tested the hypothesis that acute superoxide scavenging would restore the reduced baroreflex sensitivity in renovascular hypertension. Male Wistar rats underwent 2-Kidney-1-Clip (2K1C) or sham surgery and were maintained untouched for six weeks to develop hypertension. After six weeks, animals from the 2K1C group were hypertensive when compared to the sham group (165±9 vs. 108±7mm Hg, P<0.05). As a proof of principle for the hypertension model adopted, animals from the 2K1C group presented increased non-clipped kidney and cardiac mass index and reduced clipped kidney mass index. Regarding baroreflex, 2K1C rats presented diminished baroreflex sensitivity when compared to the sham group (2K1C+saline: -1.61±0.15 vs. sham+saline: -2.79±0.24bpm mm Hg(-1), p<0.05). Moreover, acute administration of Vitamin C (150mg/Kg, i.v.) restored baroreflex sensitivity in 2K1C rats (2K1C+Vit C: -3.08±0.37 vs. 2K1C+saline: -1.61±0.15bpm mm Hg(-1), p<0.05). Furthermore, administration of apocynin (30μg/Kg, i.v.), a NADPH oxidase inhibitor, also improved baroreflex sensitivity in the 2K1C group (2K1C+apocynin: -2.81±0.24 vs. 2K1C+saline: -1.61±0.15bpm mm Hg(-1), p<0.05). In addition, autonomic blockade with either methylatropine or propranolol reduced the changes in heart rate to the same extent in all groups suggesting that improved baroreflex sensitivity by antioxidants were mediated by improvement in autonomic function. Taken together, these data suggest that NADPH oxidase-derived reactive oxygen species are involved in the blunted baroreflex sensitivity in renovascular hypertension and that acute scavenging of superoxide restores baroreflex sensitivity.
在某些病理情况下，如高血压，自主血压控制受损导致压力反射敏感性改变。在本研究中，我们假设急性超氧化物清除会恢复肾血管性高血压中降低的压力反射敏感性。雄性 Wistar 大鼠接受 2 肾 1 夹（2K1C）或假手术，并保持 6 周以发展为高血压。6 周后，与假手术组相比，2K1C 组动物表现出高血压（165±9 对 108±7mmHg，P<0.05）。作为采用的高血压模型的原理证明，2K1C 组动物的非夹闭肾脏和心脏质量指数增加，而夹闭肾脏质量指数降低。关于压力反射，与假手术组相比，2K1C 大鼠的压力反射敏感性降低（2K1C+盐水：-1.61±0.15 对 sham+盐水：-2.79±0.24bpm·mmHg（-1），p<0.05）。此外，急性给予维生素 C（150mg/kg，静脉注射）可恢复 2K1C 大鼠的压力反射敏感性（2K1C+Vit C：-3.08±0.37 对 2K1C+盐水：-1.61±0.15bpm·mmHg（-1），p<0.05）。此外，给予 NADPH 氧化酶抑制剂 apocynin（30μg/kg，静脉注射）也可改善 2K1C 组的压力反射敏感性（2K1C+apocynin：-2.81±0.24 对 2K1C+盐水：-1.61±0.15bpm·mmHg（-1），p<0.05）。此外，用甲基阿托品或普萘洛尔进行自主神经阻断可使所有组的心率变化程度相同，这表明抗氧化剂改善压力反射敏感性是通过改善自主功能介导的。综上所述，这些数据表明 NADPH 氧化酶衍生的活性氧参与了肾血管性高血压中压力反射敏感性的降低，而急性清除超氧化物可恢复压力反射敏感性。
