The search for a factor that regulates renal sodium excretion in response to increased blood volume, a NH, stimulated by the experiments of deWardener et al. has produced a huge body of literature, which can no longer be reviewed in a single article. This review, an update of an earlier one , emphasizes how the search for a NH converged with studies of the mechanism of increased vascular resistance in hypertension, resulting in the discovery of EDLF(s) (Figure??(Figure1).1). This important discovery has widespread physiologic and pathophysiologic implications and explains, at least in part, the highly conserved nature of the ouabain binding site on membrane Na, K ATPase.
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