Influence of the at 2 receptor on the L-arginine-nitric oxide pathway and effects of (-)-epicatechin on HUVECs from women with preeclampsia

Pregnancy is a state of vasodilation mediated by nitric oxide (NO). This vasodilation is impaired in women with preeclampsia, and an alteration in the L-arginine-NO pathway may be a causal factor. The production of NO and arginase activity were investigated in plasma and human umbilical vein endothelial cells (HUVECs) from women with preeclampsia, which were associated with arginase II, eNOS, caveolin, angiotensin 1 and 2 receptor expression (AT 1 R and AT 2 R, respectively). The effect of (-)-epicatechin on arginase activity and production of anion superoxide in HUVEC also were investigated. Healthy volunteer non-pregnant (HV), normal pregnant (NP) and preeclamptic (PE) women were recruited for this study. Higher values of nitrite/nitrate (NO 2 /NO 3) were detected in the plasma from PE women as opposed to HV and NP. Lower arginase activity in PE versus HV or NP women was observed. HUVECs from PE women showed lower values of NO 2 /NO 3, higher activity of arginase and higher expression of AT 1 R and AT 2 R than HUVECS from NP women. Interestingly, arginase activity was associated with AT 2 R stimulation; indeed this activity and the high NADPH (nicotinamide adenine dinucleotide phosphate) oxidase activity in HUVECs from PE women can uncouple the production or inactivation of NO. However, we demonstrated that (-)-epicatechin could lead to a decrease in the activity of both enzymes.