Platelet function and fibrinolytic activity in hypertension: differential effects of calcium antagonists and beta-adrenergic receptor blockers.
Platelet function was investigated in healthy volunteers and patients with essential hypertension by measurement of thresholds for ADP and adrenaline-induced aggregation and plasma concentrations of platelet factor 4 (PF-4) and beta-thromboglobulin (beta-TG) after administration of antihypertensive drugs. Fibrinolytic activity was investigated by the euglobulin clot lysis time (ECLT) and tissue plasminogen activator (t-PA) activity. Compared to normotensive controls, patients with essential hypertension showed increased aggregation as evidenced by a decrease in ADP thresholds for ex vivo platelet aggregation. ECLT was significantly prolonged and t-PA significantly lowered, indicating impaired fibrinolytic activity in mild hypertension. In different studies, we have shown that various antihypertensive drug regimens differ in their effects on platelet function and fibrinolytic activity when given to healthy volunteers or patients with mild-to-moderate essential hypertension. In normal volunteers, treatment with the calcium antagonists verapamil, nifedipine, and felodipine lowered plasma concentrations of PF-4 and beta-TG, indicating a reduced platelet activity in vivo. Fibrinolytic activity was not influenced by calcium antagonist treatment in the normal volunteers. Interestingly, however, t-PA increased significantly in the hypertensive group. When compared to placebo or beta 1-selective blockers, propranolol, a non-selective beta-adrenergic blocker without partial agonist activity, reduced ADP and adrenaline threshold values for ex vivo platelet aggregation in hypertensive subjects and impaired fibrinolytic activity in the normal volunteers as well as in the hypertensive groups by increasing ECLT and reducing t-PA. Hypothetically, the effects of antihypertensive drugs on platelet function and fibrinolytic activity could be of importance for their proposed actions on cardiovascular morbidity and mortality.
Winther
K
K
Department of Clinical Chemistry, Frederiksberg and Hvidovre Hospital, Copenhagen, Denmark.
Gleerup
G
G
Hedner
T
T
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010959:Tissue Plasminogen Activator / Q000187:drug effects / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D010959:Tissue Plasminogen Activator