Seto Shinji, Nagao Shoichi, Ozeki Shin-Ichiro, Tetsuo Hirokuni, Akahoshi Masazumi, Yano Katsusuke
Department of Cardiovascular Medicine, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
J Cardiovasc Pharmacol. 2006 May;47(5):680-5. doi: 10.1097/01.fjc.0000211759.21518.d0.
We examined whether central nitric oxide is involved in blood pressure (BP) regulation in deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt rats were intracerebroventricularly infused (ICV) NG-monomethyl L-arginine (L-NMMA) for 4 weeks at either low (0.08 mg/kg/d; n = 8) or high (0.16 mg/kg/d; n = 8) dose. Saline ICV (n = 9) and intraperitoneal infused L-NMMA (low, n = 6; high dose, n = 6) were served as controls. Also, L-NMMA ICV (low, n = 6; high dose, n = 6) was conducted in normal rats. At week 3 and after, DOCA-salt with low L-NMMA ICV showed a higher BP than saline ICV (at week 4: 167.4 +/- 3.6 vs. 150.3 +/- 3.9 mm Hg, P < 0.01); this difference of BP was cancelled after ganglionic block. High L-NMMA ICV did not affect the trend of BP; however, it caused a reduced amount of saline drinking and a less estimated sodium retention than saline or low L-NMMA ICV (for 3 wk; 47.5 +/- 1.1 vs. 66.0 +/- 3.7 and 61.7 +/- 2.5 mmol, P < 0.01). In normal rats, high, but not low, L-NMMA ICV elevated BP with no effect on drinking behavior. Intraperitoneal infused L-NMMA did not affect the development of hypertension and/or sodium balance. These data suggested that, in DOCA-salt, central nitric oxide is involved in BP regulation through the dual action on sympathetic nervous activity and sodium balance.
我们研究了中枢一氧化氮是否参与醋酸脱氧皮质酮(DOCA)-盐性高血压的血压(BP)调节。DOCA-盐大鼠经脑室内注入(ICV)低剂量(0.08mg/kg/d;n = 8)或高剂量(0.16mg/kg/d;n = 8)的NG-单甲基-L-精氨酸(L-NMMA),持续4周。脑室内注入生理盐水(n = 9)和腹腔内注入L-NMMA(低剂量,n = 6;高剂量,n = 6)作为对照。此外,在正常大鼠中进行了低剂量(n = 6)和高剂量(n = 6)的L-NMMA脑室内注入实验。在第3周及之后,低剂量L-NMMA脑室内注入的DOCA-盐大鼠血压高于脑室内注入生理盐水的大鼠(第4周时:167.4±3.6 vs. 150.3±3.9 mmHg,P < 0.01);神经节阻断后,这种血压差异消失。高剂量L-NMMA脑室内注入不影响血压趋势;然而,与脑室内注入生理盐水或低剂量L-NMMA相比,它导致饮水量减少且钠潴留估计量减少(持续3周;47.5±1.1 vs. 66.0±3.7和61.7±2.5 mmol,P < 0.01)。在正常大鼠中,高剂量而非低剂量的L-NMMA脑室内注入使血压升高,对饮水行为无影响。腹腔内注入L-NMMA不影响高血压的发展和/或钠平衡。这些数据表明,在DOCA-盐性高血压中,中枢一氧化氮通过对交感神经活动和钠平衡的双重作用参与血压调节。