Crosstalk Between Nitric Oxide and Endocannabinoid Signaling Pathways in Normal and Pathological Placentation.

Endocannabinoids are a group of endogenous lipid mediators that act as ligands of cannabinoid and vanilloid receptors, activating multiple signal transduction pathways. Together with enzymes responsible for their synthesis and degradation, these compounds constitute the endocannabinoid system (ECS), which is involved in different physiological processes in reproduction. The placenta, which is essential for the success of gestation and optimal fetal growth, undergoes constant tissue remodeling. ECS members are expressed in trophoblast cells, and current evidence suggests that this system is involved in placental development, apoptosis, and syncytialization. Impairment of endocannabinoid signaling has been associated with several pathological conditions such as intrauterine growth restriction and preeclampsia. Both clinical entities are characterized by dysregulation on vascular perfusion where nitrergic system performs a pivotal role. Nitric oxide (NO) is a potent local vasodepressor that exerts a critical role in the regulation of hemodynamic flow, contributing to the maintenance of low vascular resistance in the feto-placental circulation. NO production could be affected by different factors and growing evidence suggests that the endocannabinoid mediators may regulate nitrergic signaling. Herein, we review emerging knowledge supporting ECS-mediated regulation of NO production in normal placentation. Finally, we discuss how alterations in these systems could affect homoeostasis and contribute to the occurrence of placental-mediated pregnancy complications. Given the impact on women and perinatal heath, we will focus on current knowledge regarding the effects of ECS on nitrergic system in normal and pathological placentation.

TPRV-1 expression in human preeclamptic placenta.

Preeclampsia is a multisystem disorder unique to human pregnancy, characterized by abnormal placentation. Although its causes remain unclear, it is known that the expression of several transporters is altered. Transient receptor potential vanilloid 1 (TRPV-1) is a nonselective cation channel, present in human placenta. Here, we evaluated the expression of TRPV-1 in preeclamptic placentas. We observed a deregulation in TRPV-1 expression in these placentas which may explain the impaired Ca(2+) homeostasis found in preeclampsia.

Hypertension and the pregnancy complicated by diabetes.

Diabetes is a frequent complication of pregnancy. Type 1 diabetes is associated with an increased incidence of preeclampsia and pregnancy-induced hypertension. When renal dysfunction is present, the incidence of these complications is remarkably increased. White's class, poor glycemic control during the first half of pregnancy, and early blood pressure elevation are also independent risk factors for developing preeclampsia. Whether gestational diabetes increases the background incidence of preeclampsia is still debated. Because therapeutic interventions such as low-dose aspirin and antioxidants have not been shown to be effective, preventive measures rely on tight blood glucose control, as well as adequate blood pressure treatment.