Regulation of Constitutive and Inducible Nitric Oxide Synthase by Estrogen

to nitric oxide (NO). NO is an important free radical with multiple functions, including endothelium-dependent relaxation, neurotransmission, immunoprotectionand inflammation. In addition to the numerous regulatory functions of NO, impaired synthesis of NO seems to be a key element in several diseases, such as atherosclerosis, pulmonary hypertension, and pyloric stenosis. In contrast, excessive NO production has been associated with pathophysiological states, such as endotoxemia, stroke, multiple sclerosis. Understanding the role of NO in specific disease states could provide important therapeutic approaches in the future. Gender-dependent differences in NO synthesis suggested that NOS expression and/or activity is under the control of sex steroid hormones. Indeed, animal and clinical studies showed that estrogen treatment leads to modulation of NO production. Regulation of NO production by the different NOS isoenzymes may contribute to the observed benefits of estrogen replacement therapy (Ert) on the cardiovascular as well as on the central nervous system. This chapter will discuss the possible mechanisms of 17β-estradiol-induced regulation of NO production by the three different isoforms of NOS.