Adenosine Receptors In Gestational Diabetes Mellitus And Maternal Obesity In Pregnancy

Regulation of blood flow depends on the systemic and local release of vasoactive molecules including the endogenous nucleoside adenosine. Vasodilation caused by adenosine results from the activation of adenosine receptors (ARs) at the vascular endothelium and smooth muscle. Adenosine receptors are four subtypes, i.e. A 1 AR, A 2A AR, A 2B AR and A 3 AR, of which A 2A AR and A 2B AR activation in the endothelium lead to increased generation of nitric oxide and relaxation of the underlying smooth muscle cell layer. Adenosine also causes vasoconstriction via a mechanism involving A 1 AR activation by increasing the release of vasoconstrictors. Adenosine increases the sensitivity of vascular tissues from diseases coursing with insulin resistance, including gestational diabetes mellitus (GDM) and obesity. ARs also play a role in obesity since they modulate D-glucose homeostasis, inflammation and adipogenesis. Agonists and/or antagonists of high selectivity for ARs may result in reversing the obesity state since normalises lipolysis and insulin sensitivity. A considerable fraction of pregnant women with GDM show with pregestational obesity and/or supraphysiological gestational weight gain. These conditions associated with reduced vascular responsiveness to adenosine and insulin. However, it is unclear whether GDM plus obesity in pregnancy could worsen these alterations in the foetoplacental vascular function. This chapter summarises available findings that address the potential involvement of ARs to modulate human foetoplacental vasculature in GDM and obesity in pregnancy.