Effect of eprosartan on cytoplasmic free calcium mobilization, platelet activation, and microparticle formation in hypertension.
BACKGROUND
Hypertensive patients show greater platelet activation than do normotensive individuals. Platelet activation is characterized by increased phosphatidylserine (PS) exposure in the external hemilayer of the membrane, a larger number of platelet microparticles (PMP), and changes in intraplatelet-free calcium kinetics. This study evaluated whether eprosartan can protect against undesirable platelet activation.


METHODS
A total of 30 hypertensive patients (systolic blood pressure [SBP] 140 to 189 mm Hg; diastolic blood pressure [DBP] 90 to 109 mm Hg) without renal, liver, or cardiac organic lesions and with a mean age of 47.6 +/- 9.4 years and mean body mass index (BMI) of 27.9 +/- 3.9 kg/m2 received eprosartan (600 mg/day). They were compared with 31 normotensive individuals with a mean age of 43.3 +/- 6.7 years and a mean BMI of 26.8 +/- 3.9 kg/m2. Blood pressure measurements and platelet function changes were assessed at baseline (control and hypertensive patients) and after 1 and 2 months of eprosartan monotherapy (hypertensive patients only).


RESULTS
Significant baseline to endpoint (month 2) changes in SBP and DBP were noted in the eprosartan group (SBP: baseline 152.2 +/- 16.8 mm Hg, endpoint 142.2 +/- 16.9 mm Hg, P <.01; DBP: baseline 93.5 +/- 9.9 mm Hg, endpoint 85.8 +/- 11.9 mm Hg, P <.001). Native circulating activated platelets increased in both groups after shear stress or Ca2+ ionophore activation, and were reduced by eprosartan (after shear exposure from 104% at month 1 to 76% after 2 months of therapy). Eprosartan therapy normalized the number of microparticles after blood shear exposure (P <.01) and after exposure to Ca2+ ionophore activation (P <.05) and significantly reduced the trend for platelets to be more readily activated in hypertensive compared with normotensive subjects (baseline to endpoint change P <.001; increase/shear versus baseline P <.001). Eprosartan partially normalizes cytoplasmic-free calcium mobilization in platelets.


CONCLUSIONS
Eprosartan significantly reduces blood pressure and normalizes undesirable changes in platelet function.
Labiós
Manuel
M
Hypertension Unit, Valencia University Clinic Hospital, Valencia, Spain.
Martínez
Marcial
M
Gabriel
Francisco
F
Guiral
Victoria
V
Munoz
Anna
A
Aznar
Justo
J
D000179:Acrylates / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D015539:Platelet Activation / Q000187:drug effects*; D011446:Prospective Studies; D013314:Stress, Mechanical; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects
D000179:Acrylates; D000959:Antihypertensive Agents; D007093:Imidazoles; D013876:Thiophenes; C068373:eprosartan; D002118:Calcium