Key result
Inhibition of nitric oxide synthase with L-NAME in healthy volunteers significantly increased blood pressure (P<0.01) but did not alter platelet membrane expression of P-selectin.
Why the study?
Does intravenous L-NAME followed by l- or d-arginine alter P-selectin expression and blood pressure in healthy male volunteers?
Does intravenous L-NAME followed by l- or d-arginine alter P-selectin expression and blood pressure in healthy male volunteers?
Inhibition of nitric oxide synthase increases blood pressure but does not alter platelet membrane expression of P-selectin in healthy volunteers.
NO synthase inhibition raises BP without affecting P-selectin in healthy volunteers; leaves open its role in platelet activation in cardiovascular disease.
Inhibiting platelet and endothelial nitric oxide production favours platelet adhesion and aggregation, and arterial vasoconstriction. This study investigated the effect of NG-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 < 0.01) that was restored to pretreatment values by l- but not d-arginine. Serum levels of the soluble form decreased significantly (P = 0.001) 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.
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Ritchie et al. (2002) studied Healthy volunteers (n=12). L-NAME followed by l- or d-arginine vs. Baseline was evaluated on P-selectin expression on platelets, platelet-derived microparticles and platelet-leucocyte aggregates, and soluble P-selectin levels. Inhibition of nitric oxide synthase with L-NAME in healthy volunteers significantly increased blood pressure (P<0.01) but did not alter platelet membrane expression of P-selectin.
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