Increased levels of a humoral digitalis-like factor in deoxycorticosterone acetate-induced hypertension in the pig

Abstract

Plasma levels of an endogenous digitalis-like factor (EDLF) and atrial peptides were followed in pigs confined to metabolic cages during the development of deoxycorticosterone acetate (DOCA)-induced hypertension. During the first 2 days of DOCA treatment, urinary sodium excretion decreased and the plasma levels of renin and atrial peptide fell significantly. During this period, plasma levels of EDLF increased greater than 30-fold from a baseline of less than 0.25 to 9.72 nmol ouabain equivalents/l. Between days 2 and 5 of DOCA treatment, urinary sodium returned to pre-DOCA levels ('mineralocorticoid escape') and during this period significant increases of atrial peptide and mean arterial pressure (MAP) and a decrease in EDLF were found. Following mineralocorticoid escape there was a secondary rise in levels of EDLF and atrial peptide and both phenomena correlated with MAP (EDLF, r = 0.87, P less than 0.05; atrial peptide, r = 0.9, P less than 0.05) and with each other (r = 0.96, P less than 0.05) over a 20-day period. Acute expansion of extracellular fluid volume before DOCA elicited significant increments in plasma EDLF and atrial peptide. Volume loading during chronic DOCA treatment increased plasma EDLF significantly whereas no response of atrial peptide was detected. These results suggest that DOCA affects the reactivity of mechanisms involved in the perception of and/or response to acute changes in volume status. However, neither EDLF nor atrial peptide appear to be viable candidates as direct mediators of mineralocorticoid escape. Finally, the nature of the changes found in EDLF and atrial peptide levels during DOCA treatment suggest that these factors are involved in the long-term control of blood pressure in this model of low renin hypertension.