Different Inhibitory Potencies of Various ANF-Analogues in the Isolated Aorta from Four Rodent Species

Abstract

Five ANF (atrial natriuretic factor) analogues were tested under similar conditions for their inhibitory potency against noradrenaline induced contractions in the isolated aorta from rabbits, rats, mice and guinea-pigs. The test compounds were: rat ANF 99-126, rat ANF 103-123, [Mpr105-Ala107] rat ANF 105-126-NH2 (PL-058), human ANF 105-126 and human ANF 99-126 oxidized at Met110. The potencies of the test peptides were compared to that of the reference peptide alpha-human ANF 99-126, the potency of which was set to 1. The EC50 values for the reference peptide varied between 2.4 (rabbit) and 6.6 (rat) x 10(-10) M. The highest and lowest relative potencies of the test peptides were: rat ANF 99-126: 2.6 (rat) and 1.4 (guinea-pig); rat ANF 103-123: 1.0 (rat) and 0.005 (rabbit); PL-058: 47 (mouse) and 5 (rabbit); human ANF 105-126: 2.1 (guinea-pig) and 0.5 (rabbit); oxidized human ANF 99-126: 0.3 (guinea-pig) and 0.02 (rat). The species related differences in the relative potencies of the peptides are probably due to structural dissimilarities of the vascular ANF receptors in the different species.