Endothelial nitric oxide synthase plays a minor role in inhibition of arterial thrombus formation.
Endothelial NO synthase (eNOS) expressed in the vascular endothelium or formed within platelets was postulated to inhibit platelet activation and aggregation. We have assessed the role of eNOS in platelet aggregation in vitro and in vivo by comparison of WT and eNOS-/- mice. Aggregometer studies revealed that collagen over a concentration range of 0.36-10 microg aggregated WT and eNOS-/- platelets to the same extent (10 microg: WT 86.7+/-4.7%, eNOS-/- 91+/-12%, n=6). Collagen treatment did not result in a significant increase in cGMP formation and VASP phosphorylation. Thrombin-induced P-selectin surface expression was unchanged in eNOS-/-platelets. In line with these findings no eNOS protein was detectable within the platelets of WT mice. In vivo, bleeding time after tail tip resection tended to be shorter in eNOS/- mice (WT: 116+/-35 s; eNOS-/- 109+/-37 s, n.s). Similarly, time to occlusion of the A.carotis after focal induction of thrombosis was 501+/-76 s (WT) and 457+/-95 s (eNOS-/-) (n.s.). These data demonstrate that eNOS-deficiency minimally affects platelet aggregation and is not associated with accelerated arterial thrombosis in vivo. Thus, in the mouse endothelial NO synthase does not play a major role in the autocrine modulation of platelet function and in thrombosis of conduit vessels in vivo.
Ozüyaman
Burcin
B
Institut für Herz- und Kreislaufphysiologie, Heinrich-Heine Universität, Postfach 101007, 40001 Düsseldorf, Germany.
Gödecke
Axel
A
Küsters
Susanne
S
Kirchhoff
Elisabeth
E
Scharf
Rüdiger E
RE
Schrader
Jürgen
J
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D015815:Cell Adhesion Molecules / Q000097:blood; D003094:Collagen / Q000494:pharmacology; D006152:Cyclic GMP / Q000097:blood; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010750:Phosphoproteins / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology; D013927:Thrombosis / Q000201:enzymology* / Q000209:etiology / Q000517:prevention & control; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D003094:Collagen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D013917:Thrombin; D006152:Cyclic GMP