Soluble guanylyl cyclase activation with HMR1766 attenuates platelet activation in diabetic rats.
نویسندگان
چکیده
OBJECTIVE Platelet activation significantly contributes to cardiovascular morbidity and mortality in diabetes. An association between impaired NO-mediated platelet inhibition and platelet activation has recently been demonstrated in experimental diabetes. Guanylyl cyclase activation enhances the reduced signaling via the NO/cGMP pathway. We investigated whether chronic guanylyl cyclase activation would beneficially modulate platelet activation in experimental diabetes mellitus. METHODS AND RESULTS Diabetes was induced by streptozotocin-injection in male Wistar rats. After 2 weeks, treatment with either placebo or the guanylyl cyclase activator HMR1766 (10 mg/kg twice daily by gavage) was initiated. Two weeks later, in vivo platelet activation and in vitro platelet reactivity were assessed. Chronic treatment with HMR1766 enhanced NO/cGMP-mediated signaling in platelets from diabetic rats determined by in vivo phosphorylation of platelet vasodilator-stimulated phosphoprotein (VASP) at Ser157 and Ser239. In parallel, platelet-binding of fibrinogen, surface-expression of P-selectin, appearance of platelet-derived microparticles, and platelet-aggregates with other blood cells were significantly reduced by chronic treatment with HMR1766. CONCLUSIONS Chronic activation of soluble guanylyl cyclase in diabetic rats improved markers of platelet activation and is a rationale approach for prevention of adverse cardiovascular events in diabetes.
منابع مشابه
Increased Cytochrome P4502E1 Expression and Altered Hydroxyeicosatetraenoic Acid Formation Mediate Diabetic Vascular Dysfunction
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ورودعنوان ژورنال:
- Arteriosclerosis, thrombosis, and vascular biology
دوره 26 12 شماره
صفحات -
تاریخ انتشار 2006