Dual effect of anandamide on rat placenta nitric oxide synthesis.

Anandamide (AEA) has been reported to have pleiotropic effects on reproduction, but the mechanism by which it exerts these effects is unclear. The aim of this study is to characterize rat placental endocannabinoid system and to analyze the possible functional role of AEA in the regulation of NO levels in rat placenta during pregnancy. We found that cannabinoids receptors (CB1 and CB2), FAAH and TRPV1 were expressed in chorio-allantoic placenta. NOS activity peaked at day 13 and decreased with progression of pregnancy. Both exogenous and endogenous AEA significantly decreased NOS activity. Although pre-incubation with AM251 (CB1 antagonist) or AM630 (CB2 antagonist) had no effect, co-incubation with both antagonists induced NOS activity. Furthermore, pre-incubation with exogenous AEA and both antagonists resulted in the induction of placental NOS activity and this effect was reverted with capsazepine (selective TRPV1 antagonist). Additionally, the enhanced NO synthesis caused by capsaicin was abrogated by co-treatment with capsazepine, illustrating that NOS activity could be modulated by TRPV1. Finally, the inhibition of TRPV1 receptor by capsazepine caused a significant fall in NOS activity. These data support the concept that AEA modulates NO levels by two independent pathways: (1) diminishing the NOS activity via CBs; and (2) stimulating NO synthesis via TRPV1. We hypothesized that AEA have an important implication in the normal function of placental tissues.

African-American women have higher initial HbA1c levels in diabetic pregnancy.

OBJECTIVE: African-American women with diabetes are at greater risk for poor glycemic control outside of pregnancy. We evaluated the effect of race on glycemic control in a racially mixed population of women with diabetes entering prenatal care. RESEARCH DESIGN AND METHODS: HbA1c levels along with demographic data were collected at the first prenatal visit from a group of 234 women with preexisting diabetes. We applied logistic multivariate analysis to identify factors associated with HbA1c levels above the median for the group. RESULTS: The median HbA1c level for the group was 8%. HbA1c levels were 8.7 +/- 2.0% in African-Americans and 7.7 +/- 1.5% in Caucasians (P < 0.001). African-American racial designation was significantly and independently associated with high HbA1c when controlled for maternal age, parity, White classification, diabetes type, education, marital status, obesity, insurance type, and first trimester entry into care. The effect of race was confined to the nonobese patients, for whom the adjusted odds ratio for African-American race as a predictor of high HbA1c was 8.15 with a 95% CI of 2.41-27.58 (P = 0.001). CONCLUSIONS: We found a clear racial disparity in glycemic control among women entering prenatal care with preexisting diabetes. This study demonstrates that there generally is need for better glycemic control among reproductive-age women with diabetes, but especially among those who are African-American.

Differential expression of endocannabinoid system in normal and preeclamptic placentas: effects on nitric oxide synthesis.

Anandamide (AEA) is a lipid mediator that participates in the regulation of several reproductive functions. This study investigated the endocannabinoid system in normal (NP) and preeclamptic (PE) placentas, and analyzed the potential functional role of AEA in the regulation of nitric oxide synthesis. The protein expression and localization of NAPE-PLD, FAAH and CB1 receptor were analyzed in normal and preeclamptic pregnancies using immunoblotting and immunohistochemistry. NAPE-PLD expression was shown to be significantly higher (p < 0.05) in PE tissues than in NP. In contrast, a decrease in FAAH protein (p < 0.001) was detected in placentas collected from women with preeclampsia. Both enzymes were mainly located in the syncytiotrophoblasts from normal and preeclamptic tissues. No differences were seen in CB1 receptor from both groups of placental villous. Exogenous and endogenous AEA significantly increased NOS activity. Although pre-incubation with AM251 (CB1 antagonist) had no effect, co-incubation with both AEA and AM251 diminished NOS activity from normal term placentas. We observed increased NOS activity in placental villous from women with preeclampsia compared with normotensive pregnant women. Furthermore, NOS activity from preeclamptic tissues was diminished by co-treatment with AM251, illustrating that the NO levels could be modulated by AEA. These data suggest that AEA may be one of the factors involved in the regulation of NOS activity in normal and preeclamptic placental villous. Interestingly, the differential expression of NAPE-PLD and FAAH suggests that AEA could play an important role in the pathophysiology of PE.