Alteration of decreased plasma NO metabolites and platelet NO synthase activity by paroxetine in depressed patients.
Although major depression (MD) and cardiovascular disease (CVD) have been conclusively linked in the literature, the mechanism associating MD and CVD is yet undetermined. The purpose of this paper is to further investigate a potential mechanism involving nitric oxide (NO) and to examine the effect of the selective serotonin reuptake inhibitor paroxetine on NO production by both platelets and the endothelium. In total, 17 subjects with MD and 12 healthy controls (HCs) with no known history of cardiovascular illness completed the study. Paroxetine was administered to both the MD patients and HCs over an 8-week period, and then medication was discontinued. Blood samples were taken at various times throughout paroxetine treatment and after discontinuation. Plasma NO metabolite (NOx) levels were measured by a chemiluminescence method. Platelet endothelial NO synthase (eNOS) activity was examined through the conversion of L-[14C]arginine to L-[(14)C]citrulline. Data were analyzed using t-tests and a linear mixed effects model. Baseline levels of both plasma NOx and platelet NOS activity were significantly lower in subjects with MD compared to HCs. Throughout paroxetine treatment, plasma NOx levels increased in both HCs and MD patients. However, platelet eNOS activity decreased in HCs, while no statistically significant change was evidenced in MD patients. These data suggest that, in MD patients, decreased peripheral production of NO, a potential contributor to increased cardiovascular risk, is modified by administration of the antidepressant paroxetine.
Chrapko
Wendy
W
Department of Psychiatry, University of Alberta, Edmonton, AB, Canada.
Jurasz
Paul
P
Radomski
Marek W
MW
Archer
Stephen L
SL
Newman
Stephen C
SC
Baker
Glen
G
Lara
Nathalie
N
Le Mellédo
Jean-Michel
JM
D000328:Adult; D000704:Analysis of Variance; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000097:blood*; D017374:Paroxetine / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors