Sogni P, Yang S, Pilette C, Moreau R, Gadano A, Avenard G, Bloy C, Lebrec D
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM U-24, Hôpital Beaujon, Clichy, France.
Eur J Pharmacol. 1998 Feb 26;344(1):37-43. doi: 10.1016/s0014-2999(97)01567-7.
It has been demonstrated that hyperproduction of nitric oxide (NO) plays a major role in the vasodilatation of cirrhosis; thus, the vasodilatation might be reversed by an inhibition of NO production. Experimental studies in isolated aortic rings showed that naftazone inhibits the effects of NO production. The aim of this study was to evaluate the haemodynamic effects of acute and chronic administration of naftazone in rats with portal hypertension. Haemodynamic values were measured either before and 10 min after intravenous administration of 432 microg/kg of naftazone or after 4 days of oral administration of 10 mg/kg per day. Acute administration of naftazone significantly reduced portal pressure in portal vein-stenosed and cirrhotic rats. This reduction was related to a decrease in the resistance of the liver and collateral circulation and it was associated with an increased cardiac output. Oral administration of naftazone significantly decreased portal pressure in rats with portal vein stenosis; this decrease depended on a significant reduction of portal blood flow. In both groups, arterial pressure did not change significantly. These haemodynamic effects differed from those observed following prazosin or propranolol administration. However, these effects were similar but less marked than those observed following N-nitro-L-arginine administration in systemic and splanchnic arterial territories. In conclusion, acute and oral administration of naftazone significantly reduces portal pressure by two different mechanisms in portal hypertensive rats. The exact mechanism has, however, to be elucidated.
业已证明，一氧化氮（NO）的过度产生在肝硬化血管舒张中起主要作用；因此，抑制NO的产生可能会逆转血管舒张。在离体主动脉环上进行的实验研究表明，萘丁美酮可抑制NO产生的作用。本研究的目的是评估萘丁美酮急性和慢性给药对门静脉高压大鼠血流动力学的影响。在静脉注射432微克/千克萘丁美酮前及注射后10分钟，或在每天口服10毫克/千克、连续4天后测量血流动力学值。萘丁美酮急性给药可显著降低门静脉狭窄和肝硬化大鼠的门静脉压力。这种降低与肝脏和侧支循环阻力的降低有关，并且与心输出量增加有关。萘丁美酮口服给药可显著降低门静脉狭窄大鼠的门静脉压力；这种降低取决于门静脉血流量的显著减少。在两组中，动脉压均无显著变化。这些血流动力学效应与服用哌唑嗪或普萘洛尔后观察到的效应不同。然而，这些效应与在全身和内脏动脉区域给予N-硝基-L-精氨酸后观察到的效应相似，但程度较轻。总之，萘丁美酮急性和口服给药通过两种不同机制显著降低门静脉高压大鼠的门静脉压力。然而，确切机制有待阐明。
