Role of peroxynitrite in altered fetal-placental vascular reactivity in diabetes or preeclampsia

Oxidative stress may increase production of superoxide and nitric oxide, le ading to formation of prooxidant peroxynitrite to cause vascular dysfunctio n. Having found nitrotyrosine residues, a marker of peroxynitrite action, i n placental vessels of preeclamptic and diabetic pregnancies, we determined whether vasoreactivity is altered in these placentas and treatment with pe roxynitrite produces vascular dysfunction. The responses of diabetic, preec lamptic, and normal placentas to increasing concentrations of the vasoconst rictors U-46619 (10(-9)-10(-7) M) and ANG II (10(-9)-10(-7) M) and the vaso dilators glyceryl trinitrate (10(-9)-10(-7) M) and prostacyclin (PGI(2); 10 (-8)-10(-6) M) were compared as were responses to these agents in normal pl acentas before and after treatment with 3.16 x 10(-4) M peroxynitrite for 3 0 min. Responses to both vasoconstrictors and vasodilators were significant ly attenuated in diabetic and preeclamptic placentas compared with controls . Similarly, responses to U-46619, nitroglycerin, and PGI(2), but not ANG I I, were significantly attenuated following peroxynitrite treatment. The pre sence of nitrotyrosine residues confirmed peroxynitrite interaction with pl acental vessels. Overall, our data suggest that peroxynitrite formation is capable of attenuating vascular responses in the human placenta.