Inhibition of endothelium-dependent relaxation by hemoglobin in rabbit aortic strips: Comparison between acellular hemoglobin derivatives and cellular hemoglobins

Kunihiko Nakai, Toshio Ohta, Ichiro Sakuma, Kazuhiro Akama, Yuki Kobayashi, Satoru Tokuyama, Akira Kitabatake, Yoshikazu Nakazato, Tsuneo A. Takahashi, Sekiguchi Sadayoshi

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Hemoglobin (Hb)-based artificial oxygen carders are supposed to induce vasoconstriction through the inactivation of endothelium-derived relaxing factor (EDRF). We examined the vasoconstrictive activity of acellular Hb and cellular Hb solutions in rabbit aortic strips. Unmodified Hb, pyridoxalated Hb, bovine unmodified Hb, haptoglobin-Hb complex (Hp-Hb), and polyoxyethylene glycol-conjugated Hb (PEG-Hb) were used as acellular Hbs having different molecular masses. Cellular Hbs included liposome-encapsulated Hb and red blood cells (RBC). In the first experiment, Hb (10 ng/ml to 1 mg/ml) was cumulatively added to the tissues in which steady-state relaxation was evoked by acetylcholine (ACh) after precontraction induced by phenylephrine. Although all Hb solutions induced a dose-dependent reversal of ACh-induced relaxation, the most potent vasoconstrictlye effect was noted with acellular Hbs, and their contractile activities were almost the same independent of molecular mass. On the other hand, liposome-Hb and RBC showed reduced potencies in this order. These results indicate the importance of cellularity as the major factor determining Hb-related EDRF inactivation. In another experiment, the tissues were exposed to Hb at 0.01, 0.1, or 1 mg/ml for 30 min and ACh-induced relaxation was recorded after the complete removal of Hb in an organ bath chamber. Exposure to unmodified Hb at >0.1-mg/ml concentrations significantly reduced the ACh-induced relaxation, whereas the relaxation was not affected by PEG-Hb, Hp-Hb, liposome-Hb, or RBC. These results suggest that unmodified Hb might be persistently associated with tissues and thereby inhibit ACh-induced relaxation. From these findings, we propose two attributes of Hb-related inhibition of endothelium-dependent relaxation: Acellular Hbs inhibit EDRF more efficiently in the luminal space than cellular Hbs, and unmodified Hb can also inhibit it adluminally and/or adventitially.

Original languageEnglish
Pages (from-to)115-123
Number of pages9
JournalJournal of cardiovascular pharmacology
Volume28
Issue number1
DOIs
Publication statusPublished - 1996
Externally publishedYes

Keywords

  • Artificial oxygen carrier
  • Blood substitutes
  • Endothelium-dependent vasorelaxation
  • Hemoglobins
  • Liposome
  • Vasoconstriction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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