Endogenous digitalis-like factors

Abstract

Since the early 1960s increasing evidence has been accumulated by de Wardener [1] supporting the existence of a natriuretic hormone. Dahl et al. [2] proposed that the salt-induced hypertension in the salt-sensitive rat must be caused by a low molecular humoral factor released in response to salt ingestion. The hypertensinogenic substance could be transferred via parabiosis. It was therefore assumed to be stable and of long duration. Much support for this concept came from the work of Haddy and Overbeck [3–5] who found that Na⁺/K⁺-ATPase in vascular smooth muscle cells was chronically inhibited in hypertensive animals and in patients with low plasma renin activity. They suggested that the vasoconstriction in these various types of volume- expanded hypertension was caused by a humoral inhibitor of the sodium pump. Later the idea was put forward by Blaustein [6] and MacGregor [7] that such an natriuretic factor may also produce essential hypertension. Since a substance that binds like digitalis to the cardiac glycoside receptor site of the sodium pump could produce such effects, the term of endogenous digitalis-like activity [8–11] or digitalis-like factor (EDLF) [12] came up. This assumption is analogous to that which led to the identification of the opioid peptides (endorphins and enkephalins) as ligands of the opiate receptor [13].