July 8, 2026Circulation134 citationsOpen Access
View Full PaperRapid Regulation of Platelet Activation In Vivo by Nitric Oxide
Key Result
Acute inhibition of endogenous nitric oxide production by N(G)-monomethyl-l-arginine caused rapid platelet activation, which was reversed by exogenous NO administration.
Key Points
- This research aims to understand how nitric oxide (NO) affects platelet activation in vivo, especially during inhibition of NO production.
- Healthy volunteers received intravenous injection of N(G)-monomethyl-l-arginine to inhibit NO synthase.
- Platelet activation was measured by observing fibrinogen binding and P-selectin expression.
- Sublingual administration of glyceryl trinitrate was used to assess the effect of exogenous NO.
- Inhibition of NO production elevated blood pressure and reduced platelet VASP phosphorylation.
- Increased platelet activation was observed with enhanced fibrinogen binding and surface marker expression.
- Glyceryl trinitrate reversed the effects of NO inhibition, restoring platelet activation markers to baseline.
Structured PICO
Does acute inhibition of NO production modulate platelet activation in vivo in healthy volunteers?
P
Population
Healthy volunteers subjected to acute inhibition of nitric oxide production to assess platelet activation.
I
Intervention
Intravenous injection of the NO synthase inhibitor N(G)-monomethyl-l-arginine, followed by sublingual administration of the NO donor glyceryl trinitrate
C
Comparator
Baseline levels (pre-intervention)
O
Outcome
Platelet activation (determined by platelet binding of fibrinogen and surface expression of P-selectin, glycoprotein 53, and CD40 ligand) and NO signaling (phosphorylation of platelet vasodilator-stimulated phosphoprotein)surrogate
Acute inhibition of endogenous NO production causes rapid platelet activation in vivo, which can be reversed by exogenous NO.
Abstract
BACKGROUND: Platelet activation is a feature of many cardiovascular diseases characterized by endothelial dysfunction. The mechanistic relationship between impaired systemic nitric oxide (NO) bioavailability and platelet activation in vivo remains unclear. We investigated whether acute inhibition of NO production in humans modulates platelet activation in vivo and whether exogenous NO would counteract such an effect. METHODS AND RESULTS: Intravenous injection of the NO synthase inhibitor N(G)-monomethyl-l-arginine in healthy volunteers resulted in NO synthase inhibition as detected by increased blood pressure and by significantly reduced phosphorylation of platelet vasodilator-stimulated phosphoprotein, an indicator of NO signaling. NO synthase inhibition increased platelet activation as determined by enhanced platelet binding of fibrinogen and surface expression of P-selectin, glycoprotein 53, and CD40 ligand, demonstrating tonic inhibition of platelet activation by NO production in vivo. Sublingual administration of the NO donor glyceryl trinitrate normalized platelet VASP phosphorylation and restored markers of platelet activation to baseline levels. CONCLUSIONS: Acute inhibition of endogenous NO production in humans causes rapid platelet activation in vivo, which is reversed by exogenous NO, demonstrating that platelet function in vivo is rapidly regulated by NO bioavailability.
Cite This Study
Schäfer et al. (Tue,) conducted a other in Healthy volunteers. N(G)-monomethyl-l-arginine (NO synthase inhibitor) and glyceryl trinitrate vs. Baseline levels was evaluated on Platelet activation (platelet binding of fibrinogen and surface expression of P-selectin, glycoprotein 53, and CD40 ligand). Acute inhibition of endogenous nitric oxide production by N(G)-monomethyl-l-arginine caused rapid platelet activation, which was reversed by exogenous NO administration.