Molecular dimensions of Hb-based O2 carriers determine constriction of resistance arteries and hypertension
Molecular dimensions of Hb-based O2 carriers determine constriction of resistance arteries and hypertension
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DOI：
10.1152/ajpheart.2000.279.3.h908
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发表时间：
2000-09-01
影响因子：
4.8
通讯作者：
Intaglietta, M
中科院分区：
文献类型：
--
作者：
Sakai, H;Hara, H;Intaglietta, M
在清醒仓鼠背部皮褶模型上研究了血红蛋白（Hb）基氧载体分子尺寸对阻力动脉直径（A（0），158 ± 21 μ m）和动脉血压的影响。合成了交联血红蛋白（XLHb）、聚乙二醇（PEG）结合血红蛋白（Hb）、羟乙基淀粉结合血红蛋白（XLHb）、聚合血红蛋白（XLHb）和PEG修饰血红蛋白囊泡（PEG-HbV）。它们的分子直径分别为7、22、47、68和224 nm。推注7 ml/kg XLHb（5 g/dl）引起即刻高血压（3 h时+34 +/- 13 mmHg），同时A（0）直径减小（基础值的79 +/- 8%），整个微血管网络的血流量减少。小动脉直径无明显变化。输注较大的O-2载体导致血管收缩和高血压减少，PEG-HbV变化最小。阻力动脉的收缩与高血压水平相关，其反应与O-2载体的分子尺寸成正比。这些实验的潜在机制并不明显;然而，这些效应可能与不同Hb分子的扩散特性有关。
The effect of molecular dimension of hemoglobin (Hb)-based O-2 carriers on the diameter of resistance arteries (A(0), 158 +/- 21 mu m) and arterial blood pressure were studied in the conscious hamster dorsal skinfold model. Cross-linked Hb (XLHb), polyethylene glycol (PEG)-conjugated Hb, hydroxyethylstarch-conjugated XLHb, polymerized XLHb, and PEG-modified Hb vesicles (PEG-HbV) were synthesized. Their molecular diameters were 7, 22, 47, 68, and 224 nm, respectively. The bolus infusion of 7 ml/kg of XLHb (5 g/dl) caused an immediate hypertension (+34 +/- 13 mmHg at 3 h) with a simultaneous decrease in A(0) diameter (79 +/- 8% of basal value) and a blood flow decrease throughout the microvascular network. The diameter of smaller arterioles did not change significantly. Infusion of larger O-2 carriers resulted in lesser vasoconstriction and hypertension, with PEG-HbV showing the smallest changes. Constriction of resistance arteries was found to be correlated with the level of hypertension, and the responses were proportional to the molecular dimensions of the O-2 carriers. The underlying mechanism is not evident from these experiments; however, it is likely that the effects are related to the diffusion properties of the different Hb molecules.