Differential expression of endocannabinoids system in preeclampsia: effects on nitric oxide synthesis.

CELLA M, DAMIANO A, LEGUIZAMÓN G, GRASSETTI, M, RIBEIRO ML, FRANCHI AM, FARINA MG.

Santiago

Congreso; International Federation of Placenta Association (IFPA) Meeting 2010 – Fetus and Placenta: A perfect harmony; 2010

Introduction: The endocannabinoid system has been described in human placenta. Anandamide (AEA), a most important endocannabinoid, is synthesized by different pathway and degraded by the action of a fatty acid amide hydrolase (FAAH). AEA exerts part of its effects binding to CB1 or CB2 receptors. Nitric oxide (NO) could produce the observed vascular abnormalities in preeclampsia. Recently has been shown that AEA modulates NO synthesis in various tissues. Objetive: Our aim was to evaluate the differential expression of the endocannabinoid system in preeclampsia and analyze its involvement in regulating of NO synthesis. Methods: Placentas were obtained from women undergoing a cesarean section at term (NP, n=14), who exhibietd no pregnancy complications; and women with preeclampsia (PE, n=14) defined as high blood pressure (≥140/90 mmHg after 20 week gestation) and proteinuria (≥ 300mg/24h), after cesarean sections. Results: We detected the expression of CB1 receptor in NP and PE, and identify a decrease in activity and FAAH expression in PE, suggesting higher levels of AEA in this tissue. We evaluated the activity of NO synthase (NOS) and found that incubation of NP with AEA (10-8, 10-7M) increased NO synthesis (p <0.001), and this effect was reversed by co-incubation with an antagonist of CB1 (AM251, 10-6M). Later, NP were incubated with URB-597, a inhibitor of FAAH, and NOS activity was stimulated. We found that PE placenta has larger NOS activity and a CB1 receptor antagonist (AM251), was able to decrease the activity of nitric oxide synthase (p <0.05). Discussion: Our results provide new evidence that AEA is able to regulate NOS activity in human placenta throughout the CB1 receptor and suggesting that increased levels of AEA in PE, due to the sharp decrease in the activity and protein expression of FAAH, could be related with increased NO synthesis observed in this pathology.