[Potential mechanism of dextran-conjugated hemoglobin penetration inside arterial wall].
Several reports indicated that cell-free hemoglobin induced vasoconstriction. This phenomenon was due to different pharmacological (NO trapping, vasoactive agents release and endothelial uptake...) and physical (viscosity and oxidative process of cell-free hemoglobin...) factors. We have previously showed that the blood pressure increase would be due to the presence of Dex-BTC-Hb inside arterial wall. However, we do not know how hemoglobin penetrate inside arterial wall. The objective of this study was to examine the new hypothesis of hemoglobin penetration inside arterial wall dependent of endocytosis. For this reason, an endocytosis inhibitor, cytochalasin D, was tested. We measured in anesthetized guinea pigs, the evolution of mean arterial pressure (MAP) and plasma hemoglobin concentration in presence or absence of cytochalasin D (1.6 x 10(-4) M). These measurements were carried out before and after 50% isovolemic exchange transfusion (IET) with two cell-free hemoglobins: Dex-BTC-Hb (300 kDa) and stroma-free hemoglobin (64.5 kDa). The administration of Dex-BTC-Hb or stroma-free hemoglobin induced an immediate increase in MAP that peaked within 17 min after IET and returned to baseline after 120 min. cytochalasin D attenuated the elevation of MAP when administrated before Dex-BTC-Hb but not when administrated before stroma-free hemoglobin. Furthermore, without cytochalasin D, plasma hemoglobin concentration after Dex-BTC-Hb or stroma-free hemoglobin administration decreased significantly 120 min after IET. In presence of cytochalasin D, plasma hemoglobin concentration stayed constant in Dex-BTC-Hb-treated animals but not in stroma-free hemoglobin-treated animals. cytochalasin D inhibits the endocytosis in case of Dex-BTC-Hb but not in case of stroma-free hemoglobin. This would be due to the molecular weight of cell-free hemoglobin. Based on these data, we suggest that endocytosis is one of the mechanisms by which cell-free hemoglobin with high molecular weight penetrated inside vascular endothelial cells. This endocytosis would have an impact on induced hypertension.
Smani
Y
Y
Laboratoire d'hématologie et de physiologie, EA 3452, faculté de pharmacie, Université Henri Poincaré Nancy I, Nancy.
Faivre
B
B
Fries
I
I
Labrude
P
P
Vigneron
C
C
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015638:Cytochalasin D / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D006168:Guinea Pigs; D006454:Hemoglobins / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology
D003911:Dextrans; D006454:Hemoglobins; D019384:Nucleic Acid Synthesis Inhibitors; D015638:Cytochalasin D