Negative chronotropic effect of the atrial natriuretic peptide in an anesthetized dog model.

The effects of atrial natriuretic peptide (ANP) on heart rate and on the chronotropic response induced by angiotensin II were evaluated. The action of angiotensin II, injected into the sinus node artery, on heart rate was determined in anaesthetized and vagotomized dogs pretreated with beta-adrenoceptor antagonist (n = 9), before and after the infusion of physiological and pharmacological doses (10 and 50 ng/kg per min) of ANP. ANP plasma concentrations were determined by radioimmunoassay. Compared to the baseline concentration values (117 +/- 3 pg/ml), a slight increase was produced by the lower dose (293 +/- 45 pg/ml), whereas a significant augmentation was noted with the higher dose of ANP (1024 +/- 255 pg/ml). The basal heart rate and mean systemic arterial pressure were decreased (26.3 and 13.5%) during the intravenous infusion of the physiological dose of the peptide and were significantly reduced (32.5 and 29.2%, P < 0.05) by the administration of the pharmacological dose of ANP. Angiotensin II had a positive chronotropic effect (29 +/- 3 beats/min) that was significantly inhibited by the pharmacological dose of ANP. Our results suggest that ANP might have a role in the control of heart rate.