Sympathoadrenal inhibition by atrial natriuretic peptide is not attenuated during development of congestive heart failure in dogs.

The feedback control of neuroendocrine activity by cardiopulmonary blood volume is disturbed in congestive heart failure. By analyzing plasma catecholamine kinetics, we tested in 11 chronically instrumented conscious dogs whether attenuations in the sympathoadrenal inhibition induced by atrial natriuretic peptide (ANP) contributed to this disturbance. Low-output failure was brought about by continuous ventricular pacing at 265 beats/min for 2 weeks. This resulted in a decline in aortic flow by 37 +/- 5% (SEM), an increase in peripheral vascular resistance by 48 +/- 4%, a 13 +/- 3-fold elevation in plasma ANP, a 9 +/- 3-fold elevation in plasma renin activity, and an augmentation of the norepinephrine-release rate into plasma by 132 +/- 17%. During ANP infusion, the epinephrine-release rate declined by 26 +/- 5% per 10-fold elevation in plasma ANP before pacing and by 31 +/- 7% (not significantly different) after 2 weeks of pacing. Before pacing, ANP attenuated plasma renin activity and caused hypotension without a rise in norepinephrine-release rate. After 2 weeks of pacing, ANP lowered norepinephrine release (by 16 +/- 6%) without affecting blood pressure or plasma renin activity, and vascular nonresponsiveness to ANP was verified under autonomic blockade. These data indicate that, during the development of heart failure, an inhibitory action of ANP on norepinephrine release is unmasked by an ANP-specific vascular desensitization, whereas the inhibition of epinephrine release is observed throughout. It is concluded that ANP-induced sympathoadrenal inhibition is not attenuated and, therefore, does not contribute to the disturbed regulation observed early in the development of failure.