Effect of XXXX synthase inhibition on bleeding time in @entity1 .

@entity1 @entity7293 @entity842 @entity1423
Endothelium-derived @entity842 (NO) is a potent in vitro inhibitor of platelet adhesion and aggregation, but its role in regulating platelet reactivity in vivo and in @entity1 in particular is undefined. Our primary objective was to determine whether the in vivo inhibition of NO production shortens template bleeding time (BT). The hemodynamic and platelet effects of @entity7293 ( @entity7293 ), an NO synthase inhibitor, were studied in 12 normal volunteers. Forearm template BT was determined before and 15 min after the intravenous (i.v.) infusion of 4.3 mg/kg @entity7293 . @entity7293 infusion increased mean arterial pressure from 88 +/- 4 to 99 +/- 3 mm Hg (p = 0.0001). Plasma NO levels, determined by chemiluminescence, decreased 65 +/- 10% from basal values (p < 0.05), confirming inhibition of endogenous NO production. Intravenous @entity7293 shortened BT from 5.5 +/- 0.9 to 4.0 +/- 0.6 min (p = 0.026), or by 24 +/- 8% (p = 0.008). @entity7293 infusion did not significantly change ex vivo @entity1423 . To determine whether vasoconstriction affected BT, we investigated forearm blood flow (FBF; determined by venous occlusion plethymography), and template BT in 3 subjects after the local infusion of @entity7293 (2-4 mg/min intraarterially, i.a.). Intraarterial administration of @entity7293 caused a 39 +/- 3% (p = 0.006) reduction in FBF in the infused arm but did not change BT. These data show that systemic inhibition of NO production shortens BT in @entity1 . However, the precise mechanism by which @entity7293 shortens BT is not completely defined.
