Tomita T, Umegaki K, Nakamura K, Hayashi E
Thromb Res. 1984 Jul 15;35(2):219-30. doi: 10.1016/0049-3848(84)90216-0.
Aggregation of washed platelets from stroke-prone spontaneously hypertensive rats(SHRSP) was markedly reduced with the development of hypertension in comparison with age-matched normotensive Wistar Kyoto rats(WKY) (Tomita et al. Stroke 15, 70-75, 1984). The mechanism of the hypoaggregability of SHRSP platelets was studied. Ca2+-dependence of thrombin-induced aggregation and MDA formation, and Ionophore A23187-induced aggregation of the platelets from SHRSP at a hypertensive age(16-weeks) was similar to that of the aggregation of platelets from age-matched WKY. Optimum Ca2+ concentration for aggregation and MDA formation was 1-2 mM. There was no difference in aggregation in Ca2+-free medium between the two strains. The enhancement by Ca2+ of both thrombin- and Ionophore A23187- induced aggregation, however, was markedly less in SHRSP than in WKY, whereas their MDA formation was equally enhanced by Ca2+. At a prehypertensive age (4-weeks) the degree of enhancement of aggregation by Ca2+ did not differ in the two strains. The magnitude of phospholipid(PI, PC, PE) degradation, and MDA formation IN SHRSP at early- and late- hypertensive ages(11- and 17-weeks) were either the same as or greater than that of age-matched WKY. A linear correlation line between the amount of MDA formed and the degree of platelet aggregation of SHRSP shifted to the right of WKY. In addition, thrombin-induced thromboxane B2 formation in SHRSP platelets was similar to that in WKY in the concentration range of 0.22 - 0.44 U/ml, and became significantly higher at 0.65 U/ml despite severe hypoaggregability of SHRSP platelets in all the concentrations examined. The overproduction of MDA or thromboxane B2 appears to be a compensatory mechanism. These results suggest that abnormalities of SHRSP platelets at hypertensive ages are due to an impaired function of thromboxane A2 and/or calcium concerned in aggregation and secretion but not due to a defect in cyclo-oxygenase and thromboxane synthetase pathway.
