We have shown earlier that abnormal platelet aggregation in spontaneously hypertensive rats (SHR) is not caused by prostaglandins (Thromb. Res. 41, 555-566, 1986). In this study platelets from SHR and normotensive (Wistar Kyoto, WKY) rats were used to examine the role of phosphoinositides (Pins) and protein phosphorylation in increased platelet activation in hypertension. Thrombin (0.05 U/ml) induced rapid hydrolysis of phosphatidylinositol-4,5-bis-phosphate (PIP2),

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... hate (PIP), and phosphatidylinositol (PI) in (32p)-pO4 labeled platelets. However, significantly greater hydrolysis of PIP2 and PI was seen in SHR platelets than in WKY platelets (see Table). Thrombin also caused two- to three-fold increased accumulation of phosphatidic acid (PA) in SHR platelets than in WKY platelets (see Table).Thrombin caused phosphorylation of 18,000 Dalton (P18) and 47, Dalton (P47) proteins in SHR and WKY Platelets. Significantly increased phosphorylation of P47 was seen at 5, 15, 60 and 240 seconds of incubation with thrombin in SHR platelets (60%, 68%, 98% and 91%) than in WKY platelets (13%, 37%, 44% and 47%). The extent of P18 phosphorylation was same in both SHR and WKY platelets. Aspirin (500 uM) did not affect phosphorylation of P47 or P18 in SHR or WKY Platelets. These data lead us to suggest that increased turnover of Pins and increased phosphorylation of P47 are involved in abnormal platelet aggregation in SHR (Supported in part by the COHC grant #86-01-A and the Ohio University College of Osteopathic Medicine).