Effect of doxazosin gastrointestinal therapeutic system on platelet degranulation and platelet-leukocyte microaggregate formation induced by physiologic shear stress in hypertension.
BACKGROUND
In this prospective, ex vivo, single-blind study, the effect of doxazosin on platelet function was studied in patients with hypertension.


METHODS
Platelet activation by shear stress was measured in whole blood samples of 22 hypertensive patients and 22 normotensive controls, using flow cytometry. Sheared samples were evaluated for CD62 expression, microaggregate formation, and Ca2+ mobilization. Results were collected at baseline and after 1 and 2 months of single-dose (4 mg/d) extended-release doxazosin gastrointestinal therapeutic system therapy.


RESULTS
Doxazosin normalized blood pressure in hypertensive patients after 1 and 2 months of treatment. Hypertensive patients had a higher baseline percentage (mean+/-SD) of degranulated platelets (CD62+) than the normotensive control group (4.14+/-1.05 vs. 2.47+/-0.68, P<0.01). After 2 months of doxazosin gastrointestinal therapeutic system treatment, the percentage of CD62+ in the experimental group significantly decreased (P<0.05). At baseline, the number of platelet-leukocyte aggregates in vivo was greater in hypertensive patients (P<0.01); doxazosin did not normalize this measurement. Following shearing, platelet expression of CD62 increased significantly in the hypertensive group (P<0.001 vs. control). Shear stress-induced platelet activation and microaggregate formation were also greater in hypertensive patients. Intraplatelet-free calcium concentration was higher in hypertensive patients at baseline than in the normotensive group (P<0.001). At 2 months, doxazosin significantly reduced thrombin-stimulated Ca2+ mobilization in hypertensive patients (P<0.01 vs. baseline).


CONCLUSIONS
Platelets from hypertensive patients are more readily activated by shear stress and demonstrate significant alterations in cytoplasmic-free calcium mobilization. Doxazosin treatment reduced blood pressure and normalized alterations in platelet function.
Labiós
Manuel
M
Flow Cytometry Unit, Clinical Pathology Department, La Fe University Hospital, Avda Campanar 21, 46009 Valencia, Spain.
Martínez
Marcial
M
Gabriel
Francisco
F
Guiral
Victoria
V
Aznar
Justo
J
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000188:drug therapy / Q000503:physiopathology; D015550:Cell Degranulation / Q000187:drug effects; D017292:Doxazosin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D011446:Prospective Studies; D016037:Single-Blind Method; D013314:Stress, Mechanical; D016896:Treatment Outcome
D019007:P-Selectin; D017292:Doxazosin; D002118:Calcium