Shan S Q, Rosner G L, Braun R D, Hahn J, Pearce C, Dewhirst M W
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Br J Cancer. 1997;76(4):429-37. doi: 10.1038/bjc.1997.406.
The effects of intravenous diethylamine/nitric oxide (DEA/NO), a short-acting nitric oxide (NO) donor, on systemic haemodynamics, muscle and tumour blood flow (MBF and TBF) and tumour oxygenation were examined in rats bearing subcutaneous R3230Ac carcinoma in the leg. The effects of DEA/NO on the diameters of tumour-feeding and normal arterioles were evaluated in window chambers with and without implanted tumours. DEA/NO reduced mean arterial pressure (MAP) when given at doses > or = 100 nmol kg(-1), with maximal suppression at 0.5-1 min followed by return to baseline within 20 min. DEA/NO did not affect MBF except at the highest doses (500 and 1000 nmol kg(-1)). In contrast, DEA/NO reduced TBF and constricted tumour arterioles at doses > or = 100 nmol kg(-1). Tumour arteriolar vasomotion occurred in more than half the animals during hypotension and with a significantly higher frequency than in normal granulating tissue at a dose of 500 nmol kg(-1). Normal arterioles rapidly and significantly vasodilated for about 3 min and then returned to baseline. The reductions in TBF and MAP were accompanied by synchronous reduction in tumour pO2. Our findings suggest that DEA/NO decreases TBF in two ways. In the window chamber model, vascular steal occurs as normal arterioles adjacent to tumour dilate more than tumour arterioles during the initial period of hypotension. In leg tumours, the predominant mechanism is attributable to reduced perfusion pressure induced by lowered MAP, which decreases flow to the tumour, probably because of relatively higher flow resistance. The vasoconstriction and vasomotion in tumour arterioles during DEA/NO-induced hypotension may reflect differences in regulatory metabolism of NO between neoplastic and normal arterioles. Thus, intravenous injection of a short-acting NO donor, DEA/NO, decreases MAP and heart rate, leading to subsequent decreases in tumour blood flow and oxygenation.
在腿部皮下接种R3230Ac癌的大鼠中，研究了短效一氧化氮（NO）供体静脉注射二乙胺/一氧化氮（DEA/NO）对全身血流动力学、肌肉和肿瘤血流（MBF和TBF）以及肿瘤氧合的影响。在有和没有植入肿瘤的窗口小室中评估DEA/NO对肿瘤供血小动脉和正常小动脉直径的影响。当以≥100 nmol kg⁻¹的剂量给药时，DEA/NO可降低平均动脉压（MAP），在0.5 - 1分钟时抑制作用最大，随后在20分钟内恢复到基线水平。除了最高剂量（500和1000 nmol kg⁻¹）外，DEA/NO对MBF没有影响。相反，当剂量≥100 nmol kg⁻¹时，DEA/NO可降低TBF并使肿瘤小动脉收缩。在低血压期间，超过半数的动物出现肿瘤小动脉血管运动，且在500 nmol kg⁻¹剂量下，其频率显著高于正常肉芽组织。正常小动脉迅速且显著地扩张约3分钟，然后恢复到基线水平。TBF和MAP的降低伴随着肿瘤pO₂的同步降低。我们的研究结果表明，DEA/NO通过两种方式降低TBF。在窗口小室模型中，在低血压初期，与肿瘤相邻的正常小动脉比肿瘤小动脉扩张得更多，从而发生血管窃血。在腿部肿瘤中，主要机制是由于MAP降低导致灌注压力降低，这减少了流向肿瘤的血流，可能是因为肿瘤的血流阻力相对较高。DEA/NO诱导低血压期间肿瘤小动脉的血管收缩和血管运动可能反映了肿瘤性小动脉和正常小动脉之间NO调节代谢的差异。因此，静脉注射短效NO供体DEA/NO可降低MAP和心率，进而导致肿瘤血流和氧合减少。
