EVIDENCE FOR ALTERED PLATELET NITRIC-OXIDE SYNTHESIS IN ESSENTIAL-HYPERTENSION

Objectives: To determine whether platelet aggregation to collagen was abnormal in patients with essential hypertension and whether nitric oxide donors and inhibitors of nitric oxide synthesis affect platelet aggregation differently in hypertensives compared with healthy controls. Design: Platelet aggregation assays were conducted ex vivo from both hypertensive and normal subjects simultaneously. Methods: Platelet aggregation in response to collagen was measured in platelet-rich plasma from 16 patients with untreated essential hypertension and 16 healthy volunteers matched for age, sex and smoking habits. The effect of sodium nitroprusside (a nitric oxide donor) and N(G)-monomethyl-L-arginine (L-NMMA), a specific nitric oxide synthase inhibitor, was studied. Results: In healthy controlS L-NMMA caused a marked increase in platelet aggregation, whereas in hypertensive patients a small inhibition of aggregation was seen. This was significantly different from the response seen in normal controls. No difference was seen in the aggregatory response to collagen between hypertensive patients and healthy controls. Sodium nitroprusside caused inhibition of aggregation in hypertensive patients and in controls, but there was no significant difference in the degree of inhibition between the two groups. Conclusions: We conclude that in platelets from hypertensive patients there is a markedly reduced sensitivity to L-NMMA, which could be explained by a reduction in nitric oxide synthesis.