The mechanisms leading to altered systemic and renal hemodynamics and water metabolism in pregnancy are poorly understood. Recent studies suggest that nitric oxide may play a major role in these physiologic alterations. In fact, chronic nitric oxide (NO) inhibition produces an experimental model of preeclampsia in animals. The hypotheses to be tested in this study are: (1) NO is the primary mediator of peripheral arterial vasodilation in pregnancy, such that inhibition of NO will reverse the physiologic changes in systemic and renal hemodynamics and water metabolism seen in normal pregnancy; (2) specific nitric oxide synthase (NOS) isoforms have distinct roles in maintenance of hemodynamics and water metabolism in pregnancy; and (3) protaglandins maintain renal hemodynamics during NO inhibition in pregnancy. Physiological, biochemical, cellular, and molecular techniques will be utilized to test these hypotheses in pregnant rats and mice. An understanding of the physiology of normal pregnancy is essential to evaluate the pathophysiologic derangements resulting in preeclampsia, the major cause of morbidity and mortality to mother and fetus. Further knowledge in this area may lead to new therapeutic approaches, such as the use of NO donors in preeclampsia.
