Intravenous infusion of the NO synthase inhibitor L-NMMA significantly shortened template bleeding time from 5.5 to 4.0 minutes (p=0.026) in normal volunteers.
Does L-NMMA shorten bleeding time in normal volunteers?
Systemic inhibition of NO production with L-NMMA shortens bleeding time in humans, demonstrating the in vivo role of NO in regulating platelet reactivity.
Effect estimate: 24% reduction
Absolute Event Rate: 4% vs 5.5%
p-value: p=0.026
Endothelium-derived nitric oxide (NO) is a potent in vitro inhibitor of platelet adhesion and aggregation, but its role in regulating platelet reactivity in vivo and in humans 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 NG-mono-methyl-L-arginine (L-NMMA), 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 L-NMMA. L-NMMA 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 L-NMMA shortened BT from 5.5 +/- 0.9 to 4.0 +/- 0.6 min (p = 0.026), or by 24 +/- 8% (p = 0.008). L-NMMA infusion did not significantly change ex vivo platelet aggregation. 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 L-NMMA (2-4 mg/min intraarterially, i.a.). Intraarterial administration of L-NMMA 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 humans. However, the precise mechanism by which L-NMMA shortens BT is not completely defined.
Simon et al. (Tue,) conducted a other in Normal volunteers (n=12). NG-mono-methyl-L-arginine (L-NMMA) vs. Baseline (before infusion) was evaluated on Template bleeding time (BT) (24% reduction, p=0.026). Intravenous infusion of the NO synthase inhibitor L-NMMA significantly shortened template bleeding time from 5.5 to 4.0 minutes (p=0.026) in normal volunteers.