Objective: Gestational diabetes mellitus is associated with an increased risk of developing pregnancy-related hypertension, suggesting altered regulation of placental vascular function. Endocannabinoid-mediated vasodilation has previously been described in placental vessels during uncomplicated and preeclamptic pregnancy, but it remains unclear whether these responses are altered in gestational diabetes mellitus. This study investigated endocannabinoid-related vascular responses in placentas from pregnancies complicated by gestational diabetes mellitus. Design and method: Placental tissue was obtained after elective caesarean section from uncomplicated pregnancies and pregnancies complicated by gestational diabetes mellitus. Expression of enzymes involved in endocannabinoid synthesis and degradation was assessed in placental biopsies using quantitative polymerase chain reaction. Vascular reactivity was studied using wire myography in third order fetoplacental arteries from gestational diabetes mellitus pregnancies. Following preconstriction, concentration-response curves were constructed for the endogenous endocannabinoids anandamide and 2-arachidonoylglycerol, in the absence or presence of selective cannabinoid receptor type 1 and 2 antagonists. Results: Expression levels of enzymes involved in endocannabinoid synthesis and degradation did not differ between placentas from gestational diabetes mellitus pregnancies and uncomplicated pregnancies. Anandamide-induced relaxation in uncomplicated pregnancies was mediated via cannabinoid receptors type 1 and 2, while 2-arachiydonoylglycerol induced relaxation via cannabinoid receptor type 1. In fetoplacental arteries from gestational diabetes mellitus pregnancies, both endocannabinoids also induced concentration-dependent vasodilation, yet blockade of both cannabinoid receptor type 1 and 2 did not reduce these vasodilatory responses. Conclusions: Endocannabinoid mediated vasodilation in the placental circulation is preserved in gestational diabetes mellitus but appears to be dependent on non-classical cannabinoid receptor signaling. This altered pattern of placental vascular regulation may reflect disturbed control of vascular tone and could contribute to placental vascular dysfunction associated with gestational diabetes mellitus.
Tjoe-A-On et al. (Fri,) studied this question.