1. ¹Department of Psychiatry, University of Alberta, Edmonton, AB, Canada
2. ²Department of Pharmacology, University of Alberta, Edmonton, AB, Canada
3. ³Department of Medicine and Physiology, University of Alberta, Edmonton, AB, Canada

Correspondence: Dr J-M Le Mellédo, Department of Psychiatry, University of Alberta, 1E7.05 Walter C Mackenzie Health Sciences Centre, 8440-112 Street, Edmonton, AB, Canada T6G 2B7. Tel: +1 780 407 3906; Fax: +1 780 407 6672; E-mail: jean-michel.lemelledo@ualberta.ca

⁴Current address: Department of Integrative Biology and Pharmacology and Institute of Molecular Medicine, University of Texas-Houston, Houston, TX, USA

Received 20 April 2005; Revised 9 September 2005; Accepted 29 September 2005; Published online 23 November 2005.

Abstract

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-[¹⁴C]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.