NITRIC-OXIDE AND ENDOTHELIN IN PATHOPHYSIOLOGICAL SETTINGS

The role of the endothelium is now known to encompass the generation o f many potent cytokines which impact endothelial cells, adjacent tissu e such as smooth muscle cells, and distant sites in an autocrine, para crine, and endocrine manner, respectively. This review addresses two o f these cytokines, nitric oxide and endothelin, and describes how each effects the functions of endothelial cells, including regulation of p latelet aggregation and coagulation, regulation of vasomotor tone, mod ulation of inflammation, and the regulation of cellular proliferation. The emphasis is on the increasingly recognized importance of the auto crine and paracrine mechanisms by which nitric oxide and endothelin ac t. In particular, autoinduction of endothelin is proposed as a central mechanism underlying endothelin's renowned effects. Additionally, spe cific nitric oxide/endothelin interactions are discussed by which each cytokine modulates the production and actions of the other. The net e ffect observed in a variety of physiological and pathophysiological se ttings, therefore, reflects a balance of these opposing functions.