Klabunde R E, Slayton K J, Ritger R C
Department of Pharmacology, Abbott Laboratories, Abbott Park, IL 60064.
Circ Shock. 1993 May;40(1):47-52.
NG-methyl-L-arginine (NMA) has been shown to inhibit nitric oxide production in vascular endothelium in vitro, and to cause vascular constriction and pressor responses in vivo. This study evaluated the ability of NMA to restore arterial pressure in hemorrhaged rats in order to determine the role of nitric oxide in modulating vascular tone following hemorrhage. Rats were anesthetized with pentobarbital, and hemorrhaged (0.5 ml/min/100 g body weight for 2 min) to a pressure of 41 +/- 4 mm Hg (control 111 +/- 5 mm Hg). Five minutes after ending the hemorrhage, administration of NMA (30 mg/kg, i.v.) caused rapid and complete restoration of arterial pressure, due primarily to increased systemic vascular resistance. Administration of L-arginine before NMA greatly attenuated the pressor response to NMA. NMA caused similar pressor responses in nonhemorrhaged rats, which were also partially blocked by L-arginine. Cardiac output was transiently increased by NMA in hemorrhaged, but not in nonhemorrhaged, animals. These results support the hypothesis that endothelial nitric oxide production has a significant modulatory effect on vascular tone during hemorrhage, and that inhibition of nitric oxide production permits greater expression of vasoconstrictor influences.
N-甲基-L-精氨酸（NMA）已被证明在体外可抑制血管内皮细胞中一氧化氮的产生，并在体内引起血管收缩和升压反应。本研究评估了NMA恢复出血大鼠动脉血压的能力，以确定一氧化氮在出血后调节血管张力中的作用。大鼠用戊巴比妥麻醉，并以0.5 ml/分钟/100克体重的速度出血2分钟，使血压降至41±4毫米汞柱（对照组为111±5毫米汞柱）。出血结束5分钟后，静脉注射NMA（30毫克/千克）可使动脉血压迅速完全恢复，这主要是由于全身血管阻力增加所致。在注射NMA之前给予L-精氨酸可大大减弱对NMA的升压反应。NMA在未出血的大鼠中也引起类似的升压反应，L-精氨酸也可部分阻断该反应。NMA可短暂增加出血动物的心输出量，但对未出血动物则无此作用。这些结果支持以下假设：内皮细胞一氧化氮的产生在出血期间对血管张力具有显著的调节作用，并且抑制一氧化氮的产生会使血管收缩作用的表达增强。
