The roles of the guanylate cyclase-stimulating ligands nitric oxide and atrial natriuretic peptide in the regulation of blood flow in the human fetal placental circulation

Summary Cyclic GMP produced by both soluble and membrane-bound isoforms of GCs may play a central role in the regulation of blood flow in the fetal placental vessels of the human placenta. Evidence suggest that two GC-stimulating ligands NO and ANP are produced by the human placenta and modify placental vascular resistance in vitro . The NO-soluble GC system may be involved in maintaining low basal vascular resistance, modifying the effects of vasoconstrictor substances and mediating the actions of some vasodilator autacoids. Placentally-derived ANP may act locally via membrane-bound GC to attenuate the effects of vasoconstrictor autacoids and may also be released into the circulation and affect fetal cardiovascular function. The actions of both autacoids may be important in maintaining optimum intracellular levels of cGMP in fetal vascular smooth muscle. Placental NOS activity was found to be reduced in women with pre-eclampsia compared to normotensive controls. Placental pro-ANP mRNA, however, was found not to be altered with pre-eclampsia. Reduced placental production of NO, but possibly not ANP, may be a feature of PE, and may have an adverse effect on placental hemodynamic function in that condition.