Effect of nitric oxide modulation on systemic haemodynamics and platelet activation determined by P-selectin expression.
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.
Ritchie
Joan L
JL
Department of Geriatric Medicine, The Queen's University of Belfast, Belfast, UK.
Alexander
H Dennis
HD
Allen
Patrick
P
Morgan
David
D
McVeigh
Gary E
GE
D000328:Adult; D000704:Analysis of Variance; D001120:Arginine; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D013237:Stereoisomerism; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D019007:P-Selectin; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester