Terazosin: Ex vivo and in vitro platelet aggregation effects in patients with arterial hypertension

Abstract

Antihypertensive effect, platelet aggregation, and plasma lipid profile were studied in a group of 14 hypertensive patients with diastolic blood pressure between 96 and 116 mm Hg during placebo and terazosin phases. Terazosin, an alpha 1-adrenergic blocking agent, was given initially at the dosage of 1 mg daily. Then it was continued at a dosage of 2 mg daily and 5 mg daily respectively, each dosage for 4 weeks. Blood pressure was taken every 2 weeks. Ex vivo platelet aggregation induced by epinephrine, collagen, and adenosine diphosphate (ADP) were carried out twice during the first placebo phase, once at the end of each terazosin dosage, and once in the second placebo phase. Total cholesterol, HDL cholesterol, and triglycerides were measured at the end of first placebo and terazosin phases. Blood from eight patients was taken during the second placebo phase to carry out in vitro response of platelet aggregation induced by ADP, collagen, and epinephrine before and after incubation with terazosin (1, 2 and 5 micrograms/L or doxazosin (100, 200, and 500 micrograms/L for 5 min. Terazosin induced a statistically significant decrease in 14.2/8.0 mm Hg, 26.1/13.4 mm Hg, and 33.9/16.5 mm Hg in the supine position for 1, 2, and 5 mg/daily, respectively. No changes in heart rate were observed. Terazosin inhibited significant ex vivo platelet aggregation induced by epinephrine, collagen, and ADP in a range from 20% to 45% for different concentrations of inducers. Reductions in platelet aggregation seemed not to be dose dependent, as reductions were statistically equivalent for dosages of 1, 2, and 5 mg daily. Terazosin significantly reduced the level of total cholesterol (8.71%) and triglycerides (14.31%), and increased (although not significantly) levels of HDL cholesterol (3.91%). In vitro platelet aggregation was inhibited by doxazosin to a significant extent but not by terazosin.

Pharmacological Modulation of Platelet Function in Hypertension

“…58 -60 Table 2 also shows the variability in effects reported by different groups, some of whom studied purified platelets ex vivo. [61][62][63][64][65][66][67][68][69][70][71][72] There appears to be little consensus of an effect on aggregation, although other pathophysiologic mechanisms (such as fibrinolysis 51,73 ) might be influenced by these classes of drugs. Gleerup et al 70 showed that treatment with both atenolol and isradipine was associated with reduced plasminogen activator inhibitor, a molecule involved in fibrinolysis that is known to be present in platelets as well as other cells.…”

Doksazosinin Ortalama Trombosit Volümü Üzerine Etkisi

“…Hemendez R. ve arkadaşları doksazosin total kolesterol ve trigliserid üzerine düşürücü etki yaptığı gösterilmiştir (9). Yine Hemandez R ve arkadaşları başka bir çalışmalarında terozosinin anlamlı olarak total kolesterolü ve trigliseridi düşürdüğü ancak trombosit agregasyonunu inhibe etmediğini, buna karşın doksazosinin trombosit agregasyonunu inhibe ettiğini göstermişlerdir (11).…”