PLASMA FROM PREECLAMPTIC WOMEN CAUSES A RAPID, CALCIUM-SENSITIVE RELEASE OF NITRIC-OXIDE FROM VASCULAR SMOOTH-MUSCLE CELLS

Objective: To determine whether the augmented presser response in pree clampsia could be due to reduced vascular smooth muscle cell release o f the vasodilator nitric oxide, consequent to a circulating plasma fac tor(s). Methods: The study examined effect of 2% plasma from 14 patien ts with preeclampsia and 14 normal pregnant women on nitric oxide prod uction (measured as the stable nitrite metabolite) by rat pulmonary ar tery vascular smooth muscle cells. Results: Plasma from patients with preeclampsia resulted in greater nitric oxide production. The factor(s ) in plasma from patients with preeclampsia responsible for stimulatin g production was sensitive to acid, heat, and proteases, and was remov ed by charcoal stripping. The effect of exposure to plasma was rapid ( maximal production within 30 min) and differed from the time course ob served after exposure to cytokines. Nitric oxide production was increa sed by the calcium ionophore A23187, and the differential effect of pl asma from patients with preeclampsia was inhibited by a calmodulin inh ibitor. Inhibitors of nitric oxide synthase (N-methyl-L-arginine and a minoguanidine) reduced nitric oxide production. Western analysis ident ified only the inducible nitric oxide synthase isoform. Inhibition of protein synthesis did not affect nitric oxide production. Conclusions: Exposure of vascular smooth muscle cells to a circulating factor(s) i n the plasma of patients with preeclampsia resulted in a rapid calcium /calmodulin-sensitive increase in nitric oxide production. Characteriz ation studies suggested that this was via an effect on the inducible n itric oxide synthase isoform, which was present prior to exposure to p lasma.