Van de Casteele M, Hösli M, Sägesser H, Reichen J
Department of Clinical Pharmacology, University of Berne, Switzerland.
J Hepatol. 1999 Aug;31(2):300-5. doi: 10.1016/s0168-8278(99)80228-1.
BACKGROUND/AIMS: Increased intrahepatic vascular tone can be pharmacologically manipulated in isolated cirrhotic livers. Intrahepatic endothelial dysfunction may lead to a decreased production of the potent endogenous vasodilator nitric oxide in cirrhotic livers. The aims of the study were to determine whether portal pressure can be lowered in vivo by injecting nitric oxide donors glyceryl trinitrate or nitroprusside directly in the portal vein and whether this is related to a decrease in intrahepatic resistance.
In anaesthetised CCl4 cirrhotic rats, intraportal doses of glyceryl trinitrate 0.5, 1 or 5 microg/kg/ min or nitroprusside 1, 5 or 10 microg/kg/min did not decrease portal pressure but only arterial pressure. Systemic and splanchnic haemodynamics were measured before and during 15 min intraportal infusion of glyceryl trinitrate 10 microg/kg/min or nitroprusside 20 microg/kg/min.
Glyceryl trinitrate decreased portal pressure from 14.0+/-1.1 to 11.8+/-1.4 mm Hg, splanchnic perfusion pressure from 102+/-10 to 74+/-5 mm Hg and portal sinusoidal flow from 2.11+/-0.38 to 1.70+/-0.35 ml/min/g liver (all p<0.05). Nitroprusside did not decrease portal pressure significantly but led to a reduction of the splanchnic perfusion pressure (104+/-9 to 66+/-7 mm Hg) and the portal sinusoidal flow (2.39+/-0.50 to 1.77+/-0.31 ml/min/g liver; all p<0.05). Portal sinusoidal resistance was not altered by either drug.
Intraportal infusion of nitric oxide donors decreased arterial pressure more than portal pressure. Portal sinusoidal resistance remained unaffected, but the liver parenchyma became less perfused with high doses. The systemic effects of nitric oxide donating drugs prevailed.
背景/目的：在离体肝硬化肝脏中，肝内血管张力增加可通过药物手段进行调控。肝内内皮功能障碍可能导致肝硬化肝脏中强效内源性血管舒张剂一氧化氮的生成减少。本研究的目的是确定通过直接向门静脉注射一氧化氮供体硝酸甘油或硝普钠是否能在体内降低门静脉压力，以及这是否与肝内阻力降低有关。
在麻醉的四氯化碳诱导的肝硬化大鼠中，门静脉内给予剂量为0.5、1或5微克/千克/分钟的硝酸甘油或1、5或10微克/千克/分钟的硝普钠，并未降低门静脉压力，仅降低了动脉压。在门静脉内输注10微克/千克/分钟的硝酸甘油或20微克/千克/分钟的硝普钠15分钟之前和期间，测量全身和内脏血流动力学。
硝酸甘油使门静脉压力从14.0±1.1毫米汞柱降至11.8±1.4毫米汞柱，内脏灌注压从102±10毫米汞柱降至74±5毫米汞柱，门静脉窦血流量从2.11±0.38毫升/分钟/克肝脏降至1.70±0.35毫升/分钟/克肝脏（所有p<0.05）。硝普钠未显著降低门静脉压力，但导致内脏灌注压降低（从104±9毫米汞柱降至66±7毫米汞柱）和门静脉窦血流量降低（从2.39±0.50毫升/分钟/克肝脏降至1.77±0.31毫升/分钟/克肝脏；所有p<0.05）。两种药物均未改变门静脉窦阻力。
门静脉内输注一氧化氮供体对动脉压的降低作用大于对门静脉压力的降低作用。门静脉窦阻力未受影响，但高剂量时肝实质灌注减少。一氧化氮供体药物的全身效应占主导。
