Endogenous digitalis-like compounds in essential and experimental hypertension

Abstract

The hypothesis that endogenous digitalis-like compounds might participate in body sodium and water homeostasis have led us to investigate the presence in plasma of compounds interacting with digoxin antibodies in man and rats. The apparent levels of digoxin-equivalents in plasma of control subjects (n = 21) and patients with essential hypertension (n = 48) or end-stage renal failure (n = 13) were 24.7 ± 3.2, 34.4 ± 4.4 and 98.7 ± 17.4 pg/ml, p < 0.05 and p<0.01 respectively. Positive correlations were observed between systolic and diastolic blood pressure and the apparent immunoreactivity of plasma. No relationship was found with the renal Na + excretion or the plasma renin activity. The apparent digoxin-like im munoreactivity of the plasma was correlated with its ability to inhibit ouabain binding to the erythrocyte Na + pump and to reduce the renal Na +,K +-ATPase activity. In rats with experimental hypertension, the plasma cross-reactivity with antidigoxin antibodies was also enhanced when compared to control rats (71.6 ± 10.2 pg/ml, n = 12 and 57.3 ± 5.0 pg/ml, n = 33 in Na + loaded rats and in rats with reduced renal mass respectively compared to 43.4 ± 3.7 pg/ml, n = 36, p< 0.05). In spontaneously hypertensive rats (SHR), the apparent levels of digoxin- equivalents were higher than that of age-matched WKY normotensive rats. This increase was already present in prehypertensive SHR (3 week-olds) (105.8 ± 12.4 vs 40.0 ± 6.5 pg/ml, n = 9 and 8, p<0.001) and persisted after hypertension has developped (134 ± 12.6 vs 85 ± 7.9 pg/ml, n = 7 and 8, p < 0.005 in 30 week-old rats). The apparent affinity of the erythrocyte Na +,K + cotransport for intracellular Na + and the maximal rate of the Na + pump were correlated with the plasma digoxin-like levels. These results confirm the presence in plasma of compounds possessing some of the functional and structural properties of cardioactive steroids, associated with a rise in blood pressure.