Fernández M, García-Pagán J C, Casadevall M, Bernadich C, Piera C, Whittle B J, Piqué J M, Bosch J, Rodés J
Hepatic Hemodynamic Laboratory, Hospital Clínic i Provincial, Barcelona, Spain.
Gastroenterology. 1995 May;108(5):1487-95. doi: 10.1016/0016-5085(95)90698-3.
BACKGROUND/AIMS: Excessive nitric oxide biosynthesis caused by expression of inducible NO synthase has been implicated in the hyperdynamic circulation of portal hypertension. The aim of the study was to investigate whether inducible NO synthase is expressed in portal hypertension an accounts for the hyperdynamic circulation.
In study 1, NO synthase activities were measured by the conversion of L-arginine to citrulline in tissues from portal-hypertensive, cirrhotic, and sham-operated rats and from normal rats pretreated with endotoxin and after long-term administration of dexamethasone, which inhibits the expression of inducible NO synthase. In study 2, systemic and splanchnic hemodynamics (radiolabeled microspheres) and gastric blood flow (hydrogen gas clearance and reflectance spectrophotometry) were measured in portal-hypertensive rats after long-term administration of dexamethasone (0.25 mg.kg-1.day-1) or vehicle.
In study 1, constitutive and inducible NO synthase activities in portal-hypertensive or cirrhotic rats were similar to those observed in sham-operated rats. The significant increase in the inducible activity observed after endotoxin injection was prevented when rats received long-term treatment with dexamethasone. In study 2, cardiac index, portal-pressure, portal venous inflow, and gastric blood flow were similar in dexamethasone-or vehicle-treated portal-hypertensive rats.
These results to not support a role for an increased expression of the inducible NO synthase in the hyperdynamic circulation of portal hypertension.
背景/目的：诱导型一氧化氮合酶的表达所导致的过量一氧化氮生物合成与门静脉高压的高动力循环有关。本研究的目的是调查诱导型一氧化氮合酶在门静脉高压中是否表达，并解释高动力循环的原因。
在研究1中，通过测量门静脉高压大鼠、肝硬化大鼠、假手术大鼠以及用内毒素预处理并长期给予地塞米松（抑制诱导型一氧化氮合酶表达）后的正常大鼠组织中L-精氨酸向瓜氨酸的转化来测定一氧化氮合酶活性。在研究2中，对长期给予地塞米松（0.25mg·kg-1·天-1）或赋形剂后的门静脉高压大鼠测量全身和内脏血流动力学（放射性微球）以及胃血流量（氢气清除法和反射分光光度法）。
在研究1中，门静脉高压或肝硬化大鼠的组成型和诱导型一氧化氮合酶活性与假手术大鼠相似。当大鼠接受地塞米松长期治疗时，可防止内毒素注射后观察到的诱导型活性显著增加。在研究2中，地塞米松或赋形剂治疗的门静脉高压大鼠的心脏指数、门静脉压力、门静脉流入量和胃血流量相似。
这些结果不支持诱导型一氧化氮合酶表达增加在门静脉高压高动力循环中起作用。
