The effect of prostanoid precursors and inhibitors on platelet angiotensin II binding

Abstract

Pregnancy-induced hypertension is characterised by an imbalance of arachidonic acid metabolites: Prostacyclin (PGI2) is vasodilatory and a potent inhibitor of platelet reactivity. Thromboxane (TXA2) induces vasoconstriction and platelet aggregation. Previous intervention studies have been aimed at increasing vasodilatation and decreasing platelet aggregation using low dose aspirin or dietary manipulation of prostaglandins. The aim of this study was to investigate the value of combining low dose aspirin with dietary fatty acid supplementation and its effects on platelet angiotensin II binding in non-pregnant women. Sixty non-pregnant, healthy female volunteers were recruited and randomly allocated to one of six treatment regimens which included aspirin taken alone and in combination with fish oil or evening primrose oil. A control group took no treatment. Platelet AII binding was determined before and after treatment for 1 month. There was no change in platelet angiotensin II binding after 1 month in the control group or in those who received evening primrose oil or fish oil alone. A significant decrease in binding was found in those who took aspirin in combination with fish oil (P = 0.03). An increase in binding was seen in those who took aspirin only, although this was not statistically significant (P = 0.14). A decrease was found in those who took aspirin in combination with evening primrose oil but again this was not statistically significant (P = 0.07). This study found that the combined effect of low-dose aspirin and fish oil causes a significant decrease in platelet angiotensin II binding not caused by either compound taken alone. Given that angiotensin II exerts its effect in part by direct interaction with vascular AII receptors, (platelets being used as 'models' of vascular myocytes), and that pre-eclampsia is associated with major pathophysiological changes in prostanoid metabolism, these pilot data provide a basis for further investigation.