Institute of Physiology V.V.I, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Acta Physiol (Oxf). 2013 Aug;208(4):340-9. doi: 10.1111/apha.12092. Epub 2013 Apr 12.
It is well-known that salt hypertension is associated with increased oxidative stress. Since the development of salt hypertension is age-dependent, we were interested whether young and adult salt hypertensive Dahl rats differ in oxidative stress level and/or in the effects of chronic antioxidant therapy on blood pressure (BP) level and on the participation of particular vasoconstrictor/vasodilator systems in BP maintenance.
Young (5-week-old) and adult (12-week-old) salt-sensitive (Dahl-S) male rats were fed high-salt diet (5% NaCl) and drank tempol solution (2 mm) for 5 weeks. BP was monitored with radiotelemetry and vasoconstrictor/vasodilator balance was evaluated at the end of experiment. Moreover, NO synthase activity, superoxide production and lipoperoxidation were determined in heart, kidney and aorta in separate subgroups of Dahl rats.
Tempol treatment had quite opposite BP effects in young and adult Dahl-S rats. While it tended to increase BP in young salt hypertensive Dahl-S rats, it significantly lowered BP in the adult ones due to reduced sympathetic vasoconstriction. Importantly, high salt intake substantially reduced NO synthase activity in heart and kidney, and markedly increased superoxide production in kidneys and aorta of adult Dahl-S rats in which BP correlated positively with superoxide production in thoracic aorta and lipoperoxidation in kidneys.
Chronic antioxidant therapy lowered BP only in adult salt hypertensive Dahl-S rats in which superoxide levels were increased in both kidneys and aorta. Blood pressure reduction induced by chronic tempol treatment is related to attenuated sympathetic vasoconstriction rather than to augmented NO-dependent vasodilatation.
众所周知,盐性高血压与氧化应激增加有关。由于盐性高血压的发展是年龄依赖性的,我们感兴趣的是年轻和成年盐性高血压 Dahl 大鼠在氧化应激水平上是否存在差异,以及慢性抗氧化治疗对血压(BP)水平的影响,以及在维持 BP 中特定的血管收缩/血管舒张系统的参与。
年轻(5 周龄)和成年(12 周龄)盐敏感(Dahl-S)雄性大鼠给予高盐饮食(5%NaCl)并饮用 Tempo 溶液(2mm)5 周。通过无线电遥测监测血压,并在实验结束时评估血管收缩/血管舒张平衡。此外,在不同的 Dahl 大鼠亚组中测定心脏、肾脏和主动脉中的一氧化氮合酶活性、超氧化物产生和脂质过氧化。
Tempo 治疗对年轻和成年盐性高血压 Dahl-S 大鼠的血压有完全相反的影响。虽然它倾向于增加年轻盐性高血压 Dahl-S 大鼠的血压,但由于交感神经血管收缩减少,它显著降低了成年大鼠的血压。重要的是,高盐摄入显著降低了心脏和肾脏中的一氧化氮合酶活性,并显著增加了成年 Dahl-S 大鼠肾脏和主动脉中的超氧化物产生,其中 BP 与胸主动脉中的超氧化物产生和肾脏中的脂质过氧化呈正相关。
慢性抗氧化治疗仅降低了成年盐性高血压 Dahl-S 大鼠的血压,其中肾脏和主动脉中的超氧化物水平均增加。慢性 Tempo 治疗诱导的血压降低与交感神经血管收缩减弱有关,而与增强的一氧化氮依赖性血管舒张无关。