ACE-INHIBITOR EFFECTS ON PLATELET-FUNCTION IN STAGES I-II HYPERTENSION

Angiotensin II enhances platelet aggregation through activation of the G protein-linked pathway present in platelets. Studies of several ang iotensin-converting enzyme (ACE) inhibitors have demonstrated marked d ifferences on platelets. Therefore this prospective, randomized, doubl e-blind, crossover study compared the ex vivo effects of equivalent an tihypertensive doses of captopril, enalapril, and fosinopril on platel et aggregation and thromboxane B-2 (TxB(2)) formation in subjects with stage I-II essential hypertension. Nineteen male subjects with a base line mean seated blood pressure of 141 +/- 3/100 +/- 1 mm Hg were enro lled. The decline in mean arterial pressure after 4 weeks of stable do sing was 10 +/- 1, 12 +/- 1, and 11 +/- 1 mm Hg for captopril, enalapr il, and fosinopril, respectively (p = NS). There was no significant ch ange in adenosine diphosphate (ADP)-, epinephrine-, or thrombin-stimul ated platelet aggregation from baseline or be tween ACE inhibitors. Co mpared with baseline, fosinopril decreased TxB(2) concentrations 27.5- 67.6% with all stimuli after 1 and 5 min. Captopril also decreased TxB (2) formation, but this effect was stimulus and time dependent. Enalap ril consistently increased TxB(2) concentrations, independent of stimu li or time. We conclude that different ACE inhibitors have distinct ef fects on platelet TxB(2) formation without significant effects on plat elet aggregation. Fosinopril may be a direct antagonist of TxA(2) synt hase, suggesting benefit in syndromes of platelet activation or vascul ar occlusion.