Takenaka K, Yamada H, Sakai N, Ando T, Nakashima T, Nishimura Y, Okano Y, Nozawa Y
Department of Neurosurgery, Gifu University School of Medicine, Japan.
J Neurosurg. 1991 Apr;74(4):620-4. doi: 10.3171/jns.1991.74.4.0620.
To clarify the mechanism of contractive effects in arteries caused by oxyhemoglobin, changes in the concentration of cytosolic calcium [( Ca++]i) before and after exposure to oxyhemoglobin were measured in vitro in cultured vascular smooth-muscle cells obtained from rat aorta. This was accomplished by preloading these cells with a fluorescent intracellular Ca++ probe fura-2/AM. Oxyhemoglobin induced a significant elevation of [Ca++]i in vascular smooth-muscle cells which was sustained for 10 minutes. This response was completely abolished by chelating extracellular calcium with ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetra-acetic acid (EGTA). Oxyhemoglobin induced no accumulation of mass content of inositol 1,4,5-trisphosphate (IP3(1,4,5]. The oxyhemoglobin-induced elevation of [Ca++]i was not blocked by verapamil, a calcium antagonist. Serotonin induced a rapid, transient increase of [Ca++]i followed by a sustained elevation above baseline for 5 minutes. Additions of EGTA or verapamil had a small effect on the peak height of serotonin-induced [Ca++]i elevation, but the [Ca++]i level declined more quickly to the basal level in treated compared with control cells. These results indicate that oxyhemoglobin-induced [Ca++]i elevation is caused by the influx of extracellular calcium, which is independent of the verapamil-blocked voltage-gated calcium channel. The long-lasting high elevation of [Ca++]i caused by oxyhemoglobin suggests that oxyhemoglobin may contribute to the production of abnormal contractions and/or irreversible damage in vascular smooth-muscle cells.
