We investigated the effects of: 1) atrial natriuretic factor (ANF), 2) brain natriuretic peptide (BNP), and 3) endothelin (ET) on hemodynamics and renal function in an experimental model of high-output CHF in rats. CHF was produced by a large a-v fistula (ACF) between the aorta and vena cava of rats, confirmed by measuring daily urinary sodium excretion. These rats demonstrate high plasma levels of ANF and a reduced responsiveness to exogenous ANF. Some of the rats (approximately a third) display uncompensated sodium retention (RET) that leads to death from severe CHF. The rest of the rats were able to compensate and """"""""escape"""""""" from the sodium retaining state (ESC). When the ACF was surgically closed, urine volume and sodium excretion increased abruptly and plasma renin activity decreased quickly but plasma ANF levels remained high for another 12 days and then gradually decreased. Prior bilateral renal denervation did not alter these findings. The pattern of changes in plasma ANF levels suggests that it is not only a marker of the volume overload but may also be important in the natriuresis after closure of the ACF. BNP had considerable hypotensive diuretic and natriuretic effects in normal rats. These effects were completely abolished in CHF rats. Conversely, ET had marked hypertensive, antidiuretic and antinatriuretic effects in normal rats and these effects were markedly blunted in CHF rats. We conclude that: 1) ANF is an important compensatory mechanism both during and after an ACF. 2) the vascular and renal responses to vasoactive peptides, both vasoconstrictors and vasodilators, is markedly blunted in CHF. 3) Alterations in the levels of these peptides may contribute to the fluid and sodium retention in CHF.
