The nitric oxide pathway in pre-eclampsia: pathophysiological implications

Abstract

Pre-eclampsia, one of the most significant health problems in human pregnancy, complicates approximately 6-8% of all gestations and is the leading cause of fetal growth retardation, infant morbidity and mortality, premature birth and maternal death. Recent research implicates free radicals in the pathophysiology of pre-eclampsia. This review covers the biochemistry of nitric oxide (NO) and possible interactions with other free radicals. Studies in the rat show that pregnancy is associated with enhanced production and responsiveness to NO in both reproductive tissues and blood vessels. Rats infused with NG-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor) have been used as an animal model of pre-eclampsia, and the effects of steroid hormones on blood pressure in this model have been tested. Results suggest that pre-eclampsia may be a state of NO deficiency. However, in humans there seem to be contradictions regarding the involvement of NO in maternal adaptation to pregnancy. It is suggested that NO may be one of several systems that act in concert to maintain a symbiotic relationship between mother and fetus. However, the input of each system may be genetically determined.