The role of endogenous digitalis-like factor on hypertensive mechanisms in reduced renal mass hypertensive rats

Abstract

The pathophysiological role of endogenous digitalis-like factor (EDLF) on blood pressure elevation was studied in reduced renal mass (RRM) rats with saline loading for a model of volume dependent hypertension. Fifty-four male Sprague-Dawley rats were operated on to remove varying proportions of their kidney mass (3/6RRM, n = 12; 4/6RRM, n = 16; 5/6RRM, n = 13) or sham operated (control, n = 13). They were given 1% NaCl to drink for 4 weeks. Urinary EDLF (UDLF) excretions were measured by radioimmunoassay using the anti-digoxin antibody, and urine volume, urinary sodium excretion and blood pressure were recorded. Systolic blood pressure was elevated significantly at the 1st week in 5/6RRM rats (from 135 +/- 3 mmHg to 157 +/- 3 mmHg) and continued to increase gradually until the 4th week (186 +/- 8 mmHg), but this was not seen in the other three groups. Urine volume and urinary sodium excretion increased after 1% saline drinking in all groups. UDLF increased significantly at the 1st day after 1% saline drinking in all groups (control: from 2.3 +/- 0.3 to 3.8 +/- 0.2, 3/6RRM: from 2.8 +/- 0.2 to 5.0 +/- 0.2, 4/6RRM: from 3.6 +/- 0.3 to 6.9 +/- 0.4, 5/6RRM: from 3.6 +/- 0.2 to 7.6 +/- 0.6 ng.digoxin/kg/day) but returned to the basal levels 2 days later in controls (3.0 +/- 0.4 ng.digoxin/kg/day) and 2 weeks later in 3/6RRM rats (3.1 +/- 0.2 ng.digoxin/kg/day) and 4/6RRM (3.3 +/- 0.3 ng.digoxin/kg/day). UDLF only remained higher than the basal level in 5/6RRM rats (2nd week: 4.7 +/- 0.4, 3rd week: 5.7 +/- 0.7, 4th week: 5.9 +/- 0.8 ng.digoxin/kg/day). A significant positive correlation was found between UDLF and systolic blood pressure (r = 0.278, p < 0.05), and between UDLF and sodium excretion (r = 0.657, p < 0.001) in 5/6RRM rats. When daily UDLF was measured in all groups during the 1st week, the integrated UDLF for 7 days of 1% saline consumption in 5/6RRM rats was significantly higher than in controls and 3/6RRM rats, and tended to be higher than in 4/6RRM rats. Integrated UDLF correlated positively with systolic blood pressure or changes in the systolic blood pressure. From these observations, it was concluded that EDLF might induce sodium excretion and that EDLF has an important role in the pathogenesis of blood pressure elevation in 5/6RRM rats.