Platelet aggregation and in vivo shear forces.
Haemodynamic shear forces have been reported to exert direct and indirect effects on platelet reactivity. In vitro, they activate platelets leading to spontaneous or facilitated aggregation. In vivo, they stimulate the production of endothelium-derived anti-aggregatory agents. This study was designed to evaluate in hypertensive patients, before and after antihypertensive treatment, the possible role of these haemodynamic forces, determined at the brachial artery level on the ex vivo platelet aggregatory response to ADP and collagen. Platelet reactivity, evaluated by EC50 for ADP and collagen, was found to be related to blood velocity, shear rate and shear stress (p < 0.01 for each). These inverse correlations of platelet aggregation with stress levels did not depend on age, body mass index, mean blood pressure, serum cholesterol and triglycerides or haematocrit. They were also independent of platelet cytosolic Ca2+ and cyclic AMP. The changes in shear forces and in aggregatory responses to ADP and collagen induced by nitrendipine treatment for 6 months remained negatively correlated, confirming the relationships existing between haemodynamic shear forces and platelet reactivity. These results indicate that the shear antiaggregant effects, likely mediated by flow-dependent endothelium-derived factors, prevail over its direct platelet aggregating effects.
Mazeaud
M M
MM
Pharmacology, CNRS URA 1482, Faculté de Médecine Necker, Paris, France.
Levenson
J
J
Le Quan Sang
K H
KH
Simon
A
A
Devynck
M A
MA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000886:Anthropometry; D001783:Blood Flow Velocity; D015992:Body Mass Index; D001916:Brachial Artery / Q000473:pathology; D003094:Collagen / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009568:Nitrendipine / Q000494:pharmacology / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D013314:Stress, Mechanical
D008055:Lipids; D000244:Adenosine Diphosphate; D003094:Collagen; D009568:Nitrendipine