Effect of nitric oxide modulation on systemic haemodynamics and platelet activation determined by P‐selectin expression

Abstract

Summary. Inhibiting platelet and endothelial nitric oxide production favours platelet adhesion and aggregation, and arterial vasoconstriction. This study investigated the effect of N G -nitro-l-arginine methyl ester (L-NAME), a stereospecific inhibitor of nitric oxide synthesis, on P-selectin expression on platelets, platelet-derived microparticles and platelet-leucocyte aggregates, and on soluble P-selectin levels. Twelve healthy male volunteers were infused intravenously with L-NAME and then with a 10% solution of either l-or d-arginine. Blood pressure responses were recorded and whole blood and serum collected at baseline and after each infusion. P-selectin expression was analysed in all samples by flow cytometry. Serum levels of soluble P-selectin were batch analysed using an enzyme-linked immunosorbent assay at the end of the study. P-selectin expression on platelets, platelet-derived microparticles and platelet-leucocyte aggregates did not vary significantly from baseline levels following the infusion of L-NAME or l-or d-arginine. However, endothelial nitric oxide synthase inhibition caused a marked elevation of arterial blood pressure (P < 0AE01) that was restored to pretreatment values by l-but not d-arginine. Serum levels of the soluble form decreased significantly (P ¼ 0AE001) following the infusion of l-and d-arginine compared with samples taken at baseline and following L-NAME infusion. In conclusion, inhibition of constitutive nitric oxide synthase in the endothelium and platelets produced significant increases in blood pressure but did not alter platelet membrane expression of P-selectin.

L‐arginine increases dopamine transporter activity in rat striatum via a nitric oxide synthase‐dependent mechanism

“…The RDEV signal output of 1 M DA, the concentration used to measure DA transport velocity, was not changed by the addition of 400 M L-Arg during the time period of DA transport measurements. Figure 2B also shows that the negative controls D-Arg, the NOS-inactive stereoisomer of L-Arg (Ritchie et al, 2002;Suessenbacher et al, 2002), and the basic amino acid, L-Lys, were without effect on DAT activity. L-Lys, which inhibits the transport of L-Arg into neuronal cells (Westergaard et al, 1993), blocked the ability of L-Arg to increase DA transport velocities.…”

“…DA and cocaine were used at concentrations of 10 M and 1 M, respectively. D-Arg, an NOS-inactive stereoisomer of L-Arg (Ritchie et al, 2002;Suessenbacher et al, 2002), and L-Lys, a basic amino acid, were both used as negative controls at a concentration of 400 M, which was the lowest L-Arg concentration that produced an effect on DAT activity. Carboxy PTIO, ODQ, and SNAP were used at concentrations of 200 M, 10 M, and 900 M, respectively, which are similar to those used previously by other investigators (Cao and Reith, 2002a,b;Garthwaite et al, 1995;Pogun et al, 1994).…”

“…D-Arg also had no effect on DAT activity. An effect caused by L-Arg but not by its NOS-inactive stereoisomer D-Arg has been interpreted by some investigators (Ritchie et al, 2002;Suessenbacher et al, 2002) as evidence that the effect, in this case the increase in DAT activity, is NOS-dependent and perhaps mediated by NO. Taken together, these two biochemical controls suggest that the effects of L-Arg on the DAT are not caused by its basicity or some other NOS-independent interaction.…”

Zebrafish: a genetic model for hemostasis and thrombosis

“…The fibrinolytic pathways remove the fibrin formed [11] and platelets in thrombi are retracted and further cleared [12]. The vessel wall also acts as an inhibitor of hemostasis by providing a layer of endothelial cells that secrete anticoagulant and platelet inhibitory factors, such as nitric oxide [9,13–15].…”