The human adrenal synthesizes and secretes a variety of important regulatory hormones. We have shown that the adrenal cortex is a tissue rich in endogenous digoxin-like immunoreactive factor (DLIF) and that is secretes DLIF into the circulation. We have also purified DLIF to homogeneity, determined its molecular weight and chemical composition. The chemical composition of endogenous DLIF is remarkably similar to that of the cardioactive cardenolides. Several studies have demonstrated elevated levels of endogenous DLIF in serum from patients with essential hypertension (EH), pregnancy induced hypertension (PIH), and during cardiovascular dysfunction. DLIF may regulate the enzymatic activity of ouabain-sensitive sodium-potassium ATPase. Na/K-ATPase (sodium pump) is an important modulator of vascular smooth muscle tone in arterioles as well as other cardiovascular events. Inhibition of the sodium pump causes vasoconstriction which leads to systemic hypertension. Therefore, DLIF from the adrenal cortex may play a role in the etiology of EH and PIH. We propose a working hypothesis: DLIF from human adrenal cortex are endogenous inhibitors of ouabain-sensitive sodium-potassium ATPase and by this mechanism they affect blood pressure in mammals.
The aim of this project is to define the detailed molecular structure of DLIF and characterize the biological activity of this factor obtained from adrenal tissues. Characterization will be done using four independent assays of digitalis-like activity; immunoreactivity, receptor binding, sodium-potassium ATPase enzymatic activity, and sodium pump activity. This research will provide the much needed biochemical identification of DLIF from adrenal cortex, compare these factors to DLIF from plasma, and test the hypothesis that DLIF from adrenals are endogenous inhibitors of sodium-potassium ATPase. These factors may prove useful in elucidating the mechanism responsible for EH or PIH and provide much needed diagnostic markers for these diseases.
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