Sigusch H H, Ou R, Katwa L C, Campbell S E, Ganjam V K, Reddy H K, Weber K T
Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia 65212, USA.
Cardiovasc Res. 1995 Aug;30(2):291-8.
Elevations in plasma angiotensin II (AngII) are associated with an efflux of plasma macromolecules into the perivascular and contiguous interstitial space. Whether this exudative response is related to associated hypertension or another effect of AngII is uncertain. We therefore monitored plasma and cardiac lymph total protein, albumin and fibronectin and calculated transvascular clearances for total protein (TVPC) and albumin (TVAC) and lymph fibronectin transport (LFT) every 30 min in open-chested, instrumented dogs. After baseline observations were obtained over 30 min, pressor (250 ng.kg.min-1) or nonpressor (11 ng.kg.min-1) doses of AngII were given intravenously for 90 min. Saline-treated, instrumented dogs served as controls. To address a potential secondary effect of AngII on vascular protein clearance, we monitored lymph prostaglandin E2 and cGMP (a marker of released nitric oxide, NO). At > or = 30 min, each dose of AngII was associated with a significant (P < or = 0.05) and comparable increase in TVPC, TVAC and LFT over baseline, indicating that increase in protein clearance was not related to elevated arterial pressure. Lymph cGMP rose significantly (P < or = 0.05) at 30 min for each dose of AngII and remained elevated thereafter. Lymph PGE2 was increased at > or = 60 min (P < or = 0.05) but only with the pressor dose. To determine the contribution of NO and PGE2 on AngII-induced transcoronary protein clearance, each dose of AngII was accompanied by co-administration of either the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), or the cyclo-oxygenase inhibitor, indomethacin. L-NAME completely inhibited the release of cGMP and the increase in protein clearance was not seen. Indomethacin suppressed the release of PGE2, but did not prevent the increase in protein clearance. Thus, AngII-induced increase in transcoronary protein clearance is not related to arterial hypertension or the release of PGE2, but instead appears to be mediated by NO release.
血浆血管紧张素II（AngII）升高与血浆大分子物质外渗至血管周围及相邻的间质间隙有关。这种渗出反应是与相关的高血压有关，还是AngII的另一种作用，目前尚不确定。因此，我们在开胸、植入仪器的犬类中，每隔30分钟监测血浆和心脏淋巴中的总蛋白、白蛋白和纤连蛋白，并计算总蛋白（TVPC）和白蛋白（TVAC）的跨血管清除率以及淋巴纤连蛋白转运率（LFT）。在30分钟内获得基线观察值后，静脉注射升压剂量（250 ng·kg·min-1）或非升压剂量（11 ng·kg·min-1）的AngII，持续90分钟。用生理盐水处理、植入仪器的犬类作为对照。为了研究AngII对血管蛋白清除的潜在继发效应，我们监测了淋巴前列腺素E2和cGMP（一氧化氮释放的标志物，NO）。在≥30分钟时，每剂量的AngII均与TVPC、TVAC和LFT较基线水平显著（P≤0.05）且相当程度的增加相关，表明蛋白清除率的增加与动脉血压升高无关。每剂量的AngII在30分钟时淋巴cGMP显著升高（P≤0.05），此后一直保持升高。淋巴PGE2在≥60分钟时升高（P≤0.05），但仅在升压剂量时出现。为了确定NO和PGE2对AngII诱导的冠状动脉蛋白清除的作用，每剂量的AngII同时联合给予一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）或环氧化酶抑制剂吲哚美辛。L-NAME完全抑制了cGMP的释放，且未观察到蛋白清除率的增加。吲哚美辛抑制了PGE2的释放，但并未阻止蛋白清除率的增加。因此，AngII诱导的冠状动脉蛋白清除率增加与动脉高血压或PGE2的释放无关，而是似乎由NO释放介导。
