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 angiotensin-converting enzyme (ACE) inhibitors have demonstrated marked differences on platelets. Therefore this prospective, randomized, double-blind, crossover study compared the ex vivo effects of equivalent antihypertensive doses of captopril, enalapril, and fosinopril on platelet aggregation and thromboxane B2 (TxB2) formation in subjects with stage I-II essential hypertension. Nineteen male subjects with a baseline mean seated blood pressure of 141 +/- 3/100 +/- 1 mm Hg were enrolled. The decline in mean arterial pressure after 4 weeks of stable dosing was 10 +/- 1, 12 +/- 1, and 11 +/- 1 mm Hg for captopril, enalapril, and fosinopril, respectively (p = NS). There was no significant change in adenosine diphosphate (ADP)-, epinephrine-, or thrombin-stimulated platelet aggregation from baseline or between ACE inhibitors. Compared with baseline, fosinopril decreased TxB2 concentrations 27.5-67.6% with all stimuli after 1 and 5 min. Captopril also decreased TxB2 formation, but this effect was stimulus and time dependent. Enalapril consistently increased TxB2 concentrations, independent of stimuli or time. We conclude that different ACE inhibitors have distinct effects on platelet TxB2 formation without significant effects on platelet aggregation. Fosinopril may be a direct antagonist ofTxA2 synthase, suggesting benefit in syndromes of platelet activation or vascular occlusion.
Moser
L
L
Department of Pharmacy Practice, University of Utah Health Sciences Center, Salt Lake City 84112, U.S.A.
Callahan
K S
KS
Cheung
A K
AK
Stoddard
G J
GJ
Munger
M A
MA
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D013929:Thromboxane B2