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 hear t failure (CHF), display two distinct patterns of sodium excretion: so me rats develop marked sodium retention and worsening edema with urina ry excretion of sodium (U(Na)V) < 200 muEq per 24 hours, i.e., uncompe nsated CHF, whereas in others sodium balance rapidly returns to normal (U(Na)V > 1,400 muEq per 24 hours), i.e., compensated CHF. Similar pa tterns of sodium excretion are found in patients with CHF. The mechani sms underlying these responses are not fully understood. The present s tudy was designed to assess whether bradykinin plays a role in the com pensatory response to CHF. Infusions of either 10 or 50 mug/ kg per mi nute of synthetic atrial natriuretic factor (ANF)8-33 into sham-operat ed control animals produced significant increases in urine flow and fr actional excretion of sodium (FE(Na)). Infusions of ANF at the same do ses 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 wi th 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 r ats with the bradykinin antagonist HOE-140 (D-Arg,[Hyp3,Thi5,D-Tic7, O ic8]-bradykinin) given at a rate of 100 nmol/ kg per hour did not affe ct their renal response to the ANF. In addition, infusion of the brady kinin antagonist alone into compensated rats with aortocaval fistula h ad no significant effect on their basal urinary flow rate or sodium ex cretion during the infusion. These findings indicate that kinins do no t modulate either the natriuretic response to ANF or basal sodium excr etion in rats with compensated CHF.