Inactivation of endothelium-dependent relaxing factor by liposome-encapsulated or cell-free hemoglobin

• Published in: Jinko Zoki Vol. 23; no. 3; pp. 854 - 857
• Main Authors: NAKAI K., MATSUDA N., SEKIGUCHI S., OHTA T., NAKAZATO Y., TOKUYAMA S., AKAMA H., KAWAKAMI Y., TSUCHIDA E.
• Format: Journal Article
• Language: Japanese
• Published: 一般社団法人 日本人工臓器学会 1994; JAPANESE SOCIETY FOR ARTIFICIAL ORGANS
• Subjects: Blood substitutes; EDRF; Hemoglobin; Liposome; Vasoconstriction
• ISSN: 0300-0818; 1883-6097
• DOI: 10.11392/jsao1972.23.854

The inhibitory effects of cellular and acellular hemoglobin (Hb) solutions on endothelium-dependent vasorelaxation were investigated in rabbit aortic strips. The tissues were precontracted with phenylephrine, after which acetylcholine (ACh) was added to induce a steady-state relaxation. All Hb solutions cumulatively reversed ACh-induced relaxation; liposome-encapsulated Hb and washed human red cells as cellular Hb reached a maximal vasoconstriction at 1mg/ml, while 2, 3-diphosphoglycerate depleted Hb and pyridoxylated Hb as acellular Hb reached a plateau at 10μg/ml. On the other hand, increasing in oxygen affinity by pyridoxylation had little effect on this. These findings suggest that the cellularity is very important factor influencing EDRF inhibition, and that acellular Hbs are more potent vasoconstrictor than cellular Hbs by a factor of about one hundred. Liposome包埋ヘモグロビン(Hb)およびcell-free Hbによる血管内皮由来弛緩因子(EDRF)不活化作用をウサギ大動脈標本を用いて比較した. 細胞性Hbとしてliposome Hbおよびヒト新鮮赤血球を, cell-free HbとしてDPG除去Hbおよびpyridoxal 5'-phosphate (PLP)修飾Hbを用いた. 全てのHb溶液がacetylcholineによる弛緩を抑制し, 赤血球およびliposome Hbによる血管収縮は1mg/mlで最大に達したが, 一方cell-free Hbは最大収縮量に差はないものの10μg/mlで最大値となった. 従って, cell-free Hbの有するEDRF不活化作用は細胞性Hbに比べ100倍程度高いと見積られた. DPG除去HbおよびPLP-Hbの間には血管収縮作用に差は認められず, 酸素親和性の違いによるEDRF不活化の差は認められなかった. 以上の結果から, Hb溶液によるEDRF不活化の最大の要因は細胞性であり, cell-free Hbは強力な血管収縮因子となりうることが示された.