BRADYKININ DOES NOT MODULATE THE NATRIURETIC RESPONSE TO ATRIAL-NATRIURETIC-FACTOR IN RATS WITH AORTOCAVAL FISTULA

Rats with aortocaval fistula, an experimental model of congestive heart failure (CHF), display two distinct patterns of sodium excretion: some rats develop marked sodium retention and worsening edema with urinary excretion of sodium (U(Na)V) < 200 muEq per 24 hours, i.e., uncompensated CHF, whereas in others sodium balance rapidly returns to normal (U(Na)V > 1,400 muEq per 24 hours), i.e., compensated CHF. Similar patterns of sodium excretion are found in patients with CHF. The mechanisms underlying these responses are not fully understood. The present study was designed to assess whether bradykinin plays a role in the compensatory response to CHF. Infusions of either 10 or 50 mug/ kg per minute of synthetic atrial natriuretic factor (ANF)8-33 into sham-operated control animals produced significant increases in urine flow and fractional excretion of sodium (FE(Na)). Infusions of ANF at the same doses into rats with compensated CHF increased FE(Na) from 0.11+/-0.03% to a maximum of 6.10+/-1.30%, whereas the rise in FE(Na) in animals with uncompensated CHF was significantly reduced (0.05+/-0.01% to 0.59+/-0.18%) compared with sham-operated controls (0.23+/-0.05% to 8.32+/-1.0%) or the group with compensated CHF. Treatment of the compensated rats with the bradykinin antagonist HOE-140 (D-Arg,[Hyp3,Thi5,D-Tic7, Oic8]-bradykinin) given at a rate of 100 nmol/ kg per hour did not affect their renal response to the ANF. In addition, infusion of the bradykinin antagonist alone into compensated rats with aortocaval fistula had no significant effect on their basal urinary flow rate or sodium excretion during the infusion. These findings indicate that kinins do not modulate either the natriuretic response to ANF or basal sodium excretion in rats with compensated CHF.