Cell Age Distribution of Erythrocytes at the Incidence of Cerebral Stroke in Stroke-Prone Spontaneously Hypertensive Rats, and Their Glutathione Peroxidase Activity

Abstract

  To study the mechanism of the fall of glutathione peroxidase (GSH-Px) activity in erythrocyte after cerebral strokes in stroke-prone spontaneously hypertensive rats (SHRSP), erythrocytes were fractionated into low density erythrocytes (LD-E) and high density erythrocytes (HD-E) by a density gradient centrifugal method using Percoll solution, and fluctuation of the distribution ratio and changes of GSH-Px activity in fractionated erythrocytes were investigated. The distribution ratio of LD-E and HD-E in erythrocytes of SHRSP was about 4:1 at 5 weeks of age (n=6), and the distribution to HD-E increased along with aging. While the distribution ratio was changed, however, there was no change in the GSH-Px activity in both LD-E and HD-E of erythrocytes. In senile, 30-week-old SHRSP (n=4) with advanced hypertension, the GSH-Px activity in the HD-E was lower, in proportion to the increase of the distribution rate against HD-E. On the other hand, in SHRSP (n=5) having cerebral stroke, the distribution ratio of LD-E and HD-E was about 1:4. The GSH-Px activity was 31.4±2.9 units/10¹⁰ erythrocytes in LD-E, which was hardly different from the value of SHRSP without stroke (35.7±3.3 units/10¹⁰ erythrocytes). In HD-E, however, the activity was 18.2±2.2 units/10¹⁰ erythrocytes, being lower than the activity of SHRSP without stroke. At the moment when the GSH-Px activity had dropped to 17 units/mg hemoglobin, and the control diet was changed to one based on fish or a hydralazine treatment given, the activity recovered, and an increase in body weight and the distribution rate of the LD-E over HD-E was increased. It is clear from these experiments that the fall of erythrocyte GSH-Px activity observed after cerebral stroke is due to a decrease of LD-E and increase of HD-E, which has lowered activity. However, nothing definite is known on the relationship between the fall of GSH-Px activity in erythrocytes and disorder in cerebral tissue. It appears that the fall of the GSH-Px activity causes at least functional and structural changes in erythrocytes, which interfere with the delivery of oxygen to peripheral tissues, triggering oxidation stress in cerebral tissues.