Barmaki Babak, Khazaei Majid
Department of Physiology, Zabol University of Medical Sciences, Zabol, Iran.
Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Physiology, Mashhad University of Medical Sciences, Mashhad, Iran.
Int J Appl Basic Med Res. 2015 Jan-Apr;5(1):12-7. doi: 10.4103/2229-516X.149222.
Hemorrhagic shock causes more circulatory disturbances and mortality in hypertensive than normotensive subjects. In the late phase of hemorrhagic shock, nitric oxide (NO) overproduction leads to vascular decompensation. In this study, we evaluated the effect of inducible NO synthase (iNOS) inhibitor, aminoguanidine (AG), on hemodynamic parameters and serum nitrite concentration in decompensated hemorrhagic shock model in normotensive and hypertensive male rats.
Twenty-four male rats were divided into hypertensive and normotensive groups (n = 12 each). Hypertension was induced by subcutaneous injection of deoxycorticoesterone acetate (DOCA), 30 mg/kg in uninephrectomized rats. Decompensated hemorrhagic shock was induced by withdrawing blood until the mean arterial pressure (MAP) reached 40 mmHg. After 120 min, each group was assigned to aminguanidine (100 mg/kg) and control group. Hemodynamic parameters were monitored for next 60 min. Blood samples were taken before and after shock period and 60 min after treatment. Survival rate was monitored for 72 h.
Infusion of AG in normotensive animals caused a transient increase in MAP and increase of heart rate, whereas it did not affect those parameters in hypertensive animals. Hemorrhagic shock caused a significant rise in serum nitrite concentration in normotensive and hypertensive rats and infusion of AG did not significantly change it in both groups. No significant differences observed in survival rate between AG-treated and not treated groups.
It seems that inhibition of iNOS with AG does not have beneficial effects on hemodynamatic parameters and survival rate during decompensated hemorrhagic shock in normotensive and hypertensive animals.
与血压正常的受试者相比，出血性休克在高血压患者中会导致更多的循环系统紊乱和更高的死亡率。在出血性休克的晚期，一氧化氮（NO）过量产生会导致血管失代偿。在本研究中，我们评估了诱导型一氧化氮合酶（iNOS）抑制剂氨基胍（AG）对正常血压和高血压雄性大鼠失代偿性出血性休克模型的血流动力学参数和血清亚硝酸盐浓度的影响。
24只雄性大鼠分为高血压组和正常血压组（每组n = 12）。通过在单侧肾切除的大鼠皮下注射30 mg/kg醋酸脱氧皮质酮（DOCA）诱导高血压。通过放血直至平均动脉压（MAP）达到40 mmHg诱导失代偿性出血性休克。120分钟后，每组再分为氨基胍组（100 mg/kg）和对照组。接下来60分钟监测血流动力学参数。在休克期前后以及治疗后60分钟采集血样。监测72小时的存活率。
在正常血压动物中输注AG导致MAP短暂升高和心率增加，而在高血压动物中它不影响这些参数。出血性休克导致正常血压和高血压大鼠的血清亚硝酸盐浓度显著升高，输注AG在两组中均未使其发生显著变化。AG治疗组和未治疗组之间的存活率没有显著差异。
在正常血压和高血压动物的失代偿性出血性休克期间，用AG抑制iNOS似乎对血流动力学参数和存活率没有有益影响。
