Role of Endogenous Digitalis Like Factor and Renal Prostaglandins on Hypertensive Mechanism in Reduced Renal Mass Hypertensive Rats

We have previously reported that 5/6 reduced renal mass rats (RRM), a model of volume dependent hypertension, show blood pressure elevation and continuous increase of urinary endogenous digitalis like factor (EDLF) excretion compared to 4/6, 3/6 RRM and sham operated rats (Sham). On the other hand, urinary prostaglandin (PG) E? was observed to rise at about the same rate in 5/6 and 4/6 RRM. The roles of EDLF and renal PGE? were investigated in order to clarify the pathogenesis of the high blood pressure observed in 5/6 RRM. The effect of chronic intraperitoneal infusion of ouabain (0.05 mg/kg/day) for 14 days on systolic blood pressure (SBP) and urinary sodium excretion (UNaV) was investigated in 4/6 RRM and Sham. No change in SBP was observed in either 4/6 RRM with vehicle, or Sham with vehicle. In the ouabain treated groups, significant SBP elevation (126±4 to 158±8 mmHg ; p<0.05) was obser- ved in 4/6 RRM, but not in Sham. Four sixths RRM treated with ouabain maintained an augmented urinary sodium excretion, which was significantly higher than in 4/6 RRM with vehicle (p<0.05). There was a significant positive correlation between SBP and UNaV (p<0.01). Therefore, it appears that in 4/6 RRM, which show impaired renal sodium handling though their blood pressure remains within the normal range, the observed blood pressure elevation and augmentation of urinary sodium excretion may be due to the suppression of the Na-K-ATPase activity by ouabain. The effect of chronic intraperitoneal administration of indomethacin (6 mg/kg/day) for 14 days on SBP, urinary PGE? excretion and UNaV was also evaluated in 4/6 RRM and Sham. In the in- domethacin treated groups, significant SBP elevation (119±4 to 144±5 mmHg ; p<0.05) was obser- ved in 4/6 RRM, but not in Sham. No change in SBP was observed in either 4/6 RRM with vehicle, or Sham with vehicle. There was a significant negative correlation between the change in SBP and that in urinary PGE? excretion (p=0.01) in 4/6 RRM. This suggests that the augmented urinary PGE? excretion which was observed in 4/6 RRM may play a compensatory role for the blood pressure elevation. On the other hand, the change of UNaV in 4/6 RRM treated with indomethacin (-15.7±2.7mEq/kg/ day) was significantly larger than in the 4/6 RRM treated with vehicle (-8.5±1.2mEq/kg/day) (p<0.05). There was a significant positive correlation between the change of urinary PGE? excre- tion and that of UNaV (p<0.01). Moreover, there was a significant negative correlation between the change of UNaV and that of SBP (p