Effects of N^G-nitro-L-arginine on hemodynamic changes in endotoxin shock

1.tnf - α对狗血流动力学变化和循环内皮源性血管活性因子的影响给药后，平均动脉压和心脏指数显著降低，而全身（SVRI）和肺部（PVRI）血管阻力指数升高。血浆ET-1、ET-3、NOx和6-酮- pgf_ < 1α >水平在1 h时显著升高（P<0.0）。L-NNA或吲哚美辛阻断tnf - α诱导的低血压，显著升高SVRI，但对降低的心脏指数无影响。我们的数据表明，内源性ET-1可能部分促进了tnf - α诱导的SVRI和PVRI的增加，ET-3、NO和前列环素可能作为代偿性血管舒张剂。一氧化氮合酶抑制剂对脓毒症犬血流动力学变化和O_2输送的影响LPS (250ng/kg/min) 2 h可降低1 ~ 4 h的平均动脉压。L-NNA （10mg/kg）可阻断LPS诱导的低血压，但在LPS存在或不存在的情况下，可降低心脏指数、氧输送指数、动脉pH和动脉PO_2，增加全身血管阻力指数。单独给药D-NNA （10mg/kg）比单独给药L-NNA对血流动力学的影响更小（增加全身血管阻力指数和降低心脏指数）。我们的研究提供了证据，证明L-NNA可预防内毒素诱导的低血压，但可减少心输出量和氧输送，其作用部分可能是由于非特异性NO合酶无关事件。因此，临床应用NO合酶抑制剂治疗感染性休克应慎重考虑。氨基胍（AG,5mg/kg/h，持续2小时）是一种假定的iNOS抑制剂，可预防脂多糖诱导的低血压，但不降低心脏指数。因此，AG对感染性休克的治疗有一定的可能性。

1.Effects of TNF-alpha on hemodynamic changes and circulating endothelium-derived vasoactive factors in dogsAfter administration of TNF-alpha, mean arterial pressure and cardiac index significantly decreased, whereas systemic (SVRI) and pulmonary (PVRI) vascular resistance index increased. Plasma levels of ET-1, ET-3, NOx, and 6-keto-PGF_<1alpha> significantly (P<0.0) increased at 1 h. L-NNA or indomethacin blocked TNF-alpha induced hypotension and remarkably increased SVRI but did not affect decreased cardiac index. Our data suggest that endogenous ET-1 may partly contribute to TNF-alpha -induced increases in SVRI and PVRI,against which ET-3, NO,and prostacyclin may function as compensatory vasodilators.2.Effects of nitric oxide synthase inhibitor on hemodynamic change and O_2 delivery in septic dogsInfusion of LPS (250ng/kg/min) for 2 h decreased mean arterial pressure over 1-4 h. Although L-NNA (10mg/kg) blocked LPS-induced hypotension, it decreased cardiac index oxygen delivery index, arterial pH,and arterial PO_2 and increased systemic vascular resistance index in the presence or absence of LPS.Administration of D-NNA (10mg/kg) alone caused fewer hemodynamic effects (increased systemic vascular resistance index and decreased cardiac index) than L-NNA alone. Our study provides evidence that L-NNA prevents endotoxin-induced hypotension but decreases cardiac output and oxygen delivery, effects that may, in part, be due a nonspecific NO synthase-independent event. Thus clinical use of NO synthase inhibitors for the treatment of septic shock should be cautiously considered. Infusion of aminoguanidine (AG,5mg/kg/h, for 2 h), a putative inhibitor for iNOS,prevented LPS-induced hypotension and did not decrease cardiac index. Thus, AG may have some possibility for the treatment of septic shock.