Pilette C, Moreau R, Sogni P, Kirstetter P, Cailmail S, Pussard E, Lebrec D
Laboratoire d'Hémodynamique Splanchnique, Hôpital Beaujon, Clichy, France.
Eur J Pharmacol. 1996 Sep 19;312(1):63-8. doi: 10.1016/0014-2999(96)00448-7.
In portal hypertension, the role of the vasorelaxant nitric oxide (NO) in long-term splanchnic and systemic vascular tone regulation is unclear. This study examined the effects of long-term administration of a NO synthesis inhibitor on haemodynamics in portal hypertensive rats. Rats were randomly assigned to receive either water (placebo) or 100 mg/kg.day of oral N-nitro-L-arginine methylester (L-NAME) for 28 days. At 14 days, the portal vein was ligated in 10 rats from each group. At 28 days, splanchnic and systemic blood flows were measured in 20 normal and 20 portal vein stenosed rats. Plasma atrial natriuretic peptide (ANP) concentrations as well as plasma and urinary cyclic guanosine monophosphate (cGMP) levels were also measured. Porto-systemic shunts were measured in other portal vein stenosed animals that had or had not received L-NAME. Portal vein stenosed rats that received L-NAME had significantly lower portal tributary blood flow and percentages of portal-systemic shunting (7.3 +/- 0.5 versus 3.7 +/- 0.2 ml/min.100 g and 96 +/- 1 versus 68 +/- 5%, respectively) and higher hepatocollateral vascular resistance (147 +/- 10 versus 295 +/- 30 dyn.s.cm-5.100 g.10(3), respectively) than placebo portal vein stenosed rats. Portal pressure, ANP and cGMP levels did not differ between the groups. Arterial pressure was significantly higher and cardiac index lower after L-NAME than after placebo. Normal rats had similar but less marked L-NAME-induced responses than portal hypertensive rats. The presence of a long-term L-NAME-induced vasoconstriction in collateral vessels and splanchnic and systemic arterioles in portal vein stenosed rats indicates that a NO-mediated vasodilator tone may contribute to the development and the maintenance of collateral circulation as well as splanchnic and systemic vasodilation in portal hypertension. Moreover, the NO-mediated vasodilator tone in portal hypertensive animals seems to be increased.
在门静脉高压症中，血管舒张剂一氧化氮（NO）在长期内脏和全身血管张力调节中的作用尚不清楚。本研究检测了长期给予NO合成抑制剂对门静脉高压大鼠血流动力学的影响。将大鼠随机分为两组，分别给予水（安慰剂）或100mg/kg·天的口服N-硝基-L-精氨酸甲酯（L-NAME），持续28天。在第14天，每组10只大鼠结扎门静脉。在第28天，测量20只正常大鼠和20只门静脉狭窄大鼠的内脏和全身血流量。同时检测血浆心钠素（ANP）浓度以及血浆和尿液中环磷酸鸟苷（cGMP）水平。在其他已接受或未接受L-NAME的门静脉狭窄动物中测量门体分流情况。接受L-NAME的门静脉狭窄大鼠的门静脉分支血流量和门体分流百分比显著降低（分别为7.3±0.5与3.7±0.2ml/min·100g和96±1与68±5%），肝侧支血管阻力更高（分别为147±10与295±30dyn·s·cm⁻⁵·100g·10³），而安慰剂组门静脉狭窄大鼠则无此现象。两组之间门静脉压力、ANP和cGMP水平无差异。L-NAME组的动脉压显著高于安慰剂组，心脏指数则低于安慰剂组。正常大鼠对L-NAME诱导的反应与门静脉高压大鼠相似，但程度较轻。长期给予L-NAME可导致门静脉狭窄大鼠侧支血管、内脏和全身小动脉收缩，这表明NO介导的血管舒张张力可能有助于门静脉高压时侧支循环的形成和维持以及内脏和全身血管舒张。此外，门静脉高压动物中NO介导的血管舒张张力似乎有所增加。
