[Endothelin and endogenous digitalis-like substance in cardiovascular regulation: a review]

Recent findings on endothelin, an endothelium-derived vasoconstrictor substance and endogenous digitalislike Na+, K+-ATPase inhibitor (s) obtained from animal and clinical experiments are reviewed. Endothelin is one of the most potent vasoconstrictive substances ever found; the pressor responses last for more than one hour after the bolus injection in rats. Because the pressor responses have not been attenuated by any known receptor-antagonists, the vasoconstriction is mediated by the endothelin receptors. Since messenger RNA for endothelin increases with thrombin, it may be involved in the damages of blood vessels. Radioimmunoassay for endothelin revealed that immunoreactive endothelin is increased in plasma of patients with chronic renal failure. Therefore, the plasma level of endothelin can be an index for some circulatory disorders. Since the Na+, K+-ATPase inhibitor cross-reacts with antidigoxin and antiouabain antibody, it is called a digitalis-like substance. We have demonstrated that cells containing the immunoreactive-substance to antidigoxin and antiouabain antibodies are restricted in the paraventricular and supraoptic nucleus of the hypothalamus, and that the plasma digoxinlike immunoreactivity increases with intracerebroventricular and intravenous infusions of hypertonic saline in rats. Because plasma concentrations of the immunoreactive substance significantly correlate with blood pressure, the substance seems to be involved in hypertension associated with excess intake of sodium salt.