Abstract

Isolated rabbit hearts were perfused for 2 hr with Krebs' solution at 37°C, pH 7.3 to 7.35 and flow rates of 8 to 12 ml/min. H³-norepinephrine (H³NE), 10 ng/ml, was added to the perfusate, and the hearts were perfused for 15 min. The amount of H³NE accumulated in the heart was determined in the right auricle and left ventricle by scintillation counting. Total myocardial NE was determined fluorometrically. Angiotensin II (02 ng/ml) and angiotensin amide (2.0, 0.2 and 0.05 ng/ml) inhibited the uptake of H³NE. Addition of blood to the perfusate decreased the amount of inhibition obtained with peptide administration. When significant inhibition of uptake occurred, there was a potentiation of the positive chronotropic response to NE. Angiotensin also inhibited the uptake of H³-metaraminol. Several analogs of angiotensin were studied in an attempt to determine thestructural requirements needed for uptake inhibition in the heart. In general, changes in positions 1 to 7 showed good correlation between inhibition of H³NE uptake and pressor activity. However, a similar correlation was not found with peptides substituted in position 8. These analogs had pressor activities ranging from 0.1 to 10% but produced marked inhibition of H³NE accumulation. These results suggest that angiotensin receptors on sympathetic nerve endings have different structural requirements than do muscle receptors and that levels of the peptide close to normal circulating plasma levels have the ability to modulate NE inactivation by uptake processes.