title: Cytoplasmic free calcium mobilization in platelets, expression of P-selectin, phosphatidylserine, and microparticle formation, measured by whole blood flow cytometry, in hypertensive patients. Effect of doxazosin GITS.
abstract: The effects of doxazosin on expression of CD62 (P-selectin) and phosphatidylserine on platelet membrane and platelet calcium flux were studied in 50 uncomplicated essential hypertensive patients (World Health Organization stages 1-2) and 80 normotensive control subjects, matched for age, sex, and cardiovascular risk factors. Hypertensive patients showed greater in vivo platelet activation at baseline than control patients (percentage of CD62-positive platelets, 4.1+/-2.2% versus 2.4+/-1.5%, p<0.001; percentage of phosphatidylserine-positive platelets, 0.8+/-0.5% versus 0.5+/-0.3%, p<0.001). Increased platelet activation was associated with significant changes in the mobilization of free intraplatelet calcium, evaluated by a whole blood flow cytometric kinetic method. With this method, an arbitrary Ca(2+) mobilization index was defined as the ratio of cytoplasmic free calcium before activation with thrombin to the slope of the calcium removal rate following the action of the agonist. This index was significantly higher in untreated hypertensive patients than in normotensive controls (0.12+/-0.06 versus 0.05+/-0.08, p<0.001). Treatment of hypertensive patients with doxazosin gastrointestinal therapeutic system (4 mg/day as a single dose) for 2 months normalized both platelet activation and Ca(2+) mobilization. Changes in the expression of CD62 and phosphatidylserine in the platelet membrane after treatment with doxazosin gastrointestinal therapeutic system may be related to normalization of the kinetics of cytoplasmic free Ca(2+). Normalization of platelet activation may represent an additional beneficial effect to the known antihypertensive action of doxazosin gastrointestinal therapeutic system.
authors.affiliation: Hypertension Unit, Clinic University Hospital, Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Labiós
authors.forename: Marcial
authors.initials: M
authors.lastname: Martínez
authors.forename: Francisco
authors.initials: F
authors.lastname: Gabriel
authors.forename: Victoria
authors.initials: V
authors.lastname: Guiral
authors.forename: Sandra
authors.initials: S
authors.lastname: Ruiz-Aja
authors.forename: Justo
authors.initials: J
authors.lastname: Aznar
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology*; D002118:Calcium / Q000097:blood*; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000473:pathology; D003593:Cytoplasm / Q000276:immunology; D017292:Doxazosin / Q000008:administration & dosage*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D010718:Phosphatidylserines / Q000097:blood*
chemical_list: D000959:Antihypertensive Agents; D019007:P-Selectin; D010718:Phosphatidylserines; D017292:Doxazosin; D002118:Calcium