Iso-atrial natriuretic peptide (iso-rANP), a 45
amino acid peptide with a
disulfide bond between residues 23 and 39, is a newly discovered second atrial
hormone with considerable homology with
rat atrial natriuretic peptide (rANP). We have reported that
iso-rANP(1-45) has effects similar to rANP in anesthetized rats in causing
hypotension, a decrease in heart rate, and an increase in urine flow and
electrolyte excretion. In the present experiments, we found that, unlike the ring
peptide of rANP (rANP(105-121)), bolus
injections of the ring
peptide of iso-rANP (iso-rANP(23-39)) had considerable effects on the circulation but only small effects on the kidney, compared with
iso-rANP(1-45). However, the effects of iso-rANP(23-39) in causing
hypotension and decreasing heart rate were transient compared with those of
iso-rANP(1-45). When we substituted a
glycine for
arginine into the ring portion of iso-rANP at position 36, so that there were only three
amino acids different from the ring of rANP,
biological activity of iso-rANP(23-39) was retained. In our bioassay system, all of the circulatory effects and most of the renal effects of rANP are mediated via vagal sensory afferents. We found that the effects of the ring
peptide of iso-rANP on the circulation and the kidney were unchanged following
vagotomy. The results indicate that iso-rANP(23-39) mediates at least some
biological effects by membrane receptor mechanisms different from those of rANP and that the ring portion of iso-rANP probably contributes to nonvagally mediated responses of
iso-rANP(1-45).