Key result
Acute endogenous NO inhibition causes rapid platelet activation that exogenous NO reverses.
Why the study?
The mechanistic relationship between impaired systemic nitric oxide bioavailability and in vivo platelet activation in cardiovascular diseases with endothelial dysfunction was unclear.
Does acute inhibition of NO production modulate platelet activation in vivo in healthy volunteers?
Does acute inhibition of NO production modulate platelet activation in vivo in healthy volunteers?
Acute inhibition of endogenous NO production causes rapid platelet activation in vivo, which can be reversed by exogenous NO.
Supports a role for endogenous NO in suppressing platelet activation; leaves open clinical relevance in cardiovascular disease.
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.
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Schäfer et al. (2004) studied 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.
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