Vasodilator properties of a family of bioactive atrial peptides in isolated perfused rat kidneys.
The isolated Krebs-perfused rat kidney was used for the quantitative and qualitative evaluation of the family of peptides derived from rat atrial extracts. Renal resistance changes were measured in perfused rat kidneys continuously infused with norepinephrine. The low molecular weight peptide fraction from rat atrial extracts was purified to obtain six peptides. The 21 amino acid peptide, designated atriopeptin I, was previously demonstrated to be natriuretic and to relax intestinal but not vascular smooth muscle strips (in vitro) and to be an extremely weak renal spasmolytic in the isolated perfused rat kidney. On the other hand, the 23 amino acid peptide (which has a Phe-Arg carboxy-terminal extension on atriopeptin I), designated atriopeptin II, and atriopeptin III (the Phe-Arg-Tyr carboxy-terminal extension) were natriuretic and spasmolytic (in vitro) on both intestinal and vascular smooth muscle. Both atriopeptin II and III produced a profound concentration-dependent decrease in renal resistance in the norepinephrine-constricted rat kidney preparation. A comparative study of the six peptides isolated from atrial extracts indicates that the Phe-Arg or Phe-Arg-Tyr carboxy-terminal extension of the basic 21 amino acid sequence is essential for the renal vasorelaxant activity. A purified high molecular weight peptide (designated atriopeptigen) is impotent relative to the low molecular weight atriopeptin II and III as a renal spasmolytic in isolated perfused rat kidneys and reduces renal resistance only after in vitro proteolytic cleavage. Thus, the low molecular weight peptides atriopeptin II and III appear to be the active species that mediate the renal vasodilation produced by atrial extracts.
Wakitani
K
K
Currie
M G
MG
Geller
D M
DM
Needleman
P
P
D000818:Animals; D009320:Atrial Natriuretic Factor; D002645:Chickens; D003488:Cyanogen Bromide; D006325:Heart Atria / Q000032:analysis; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008970:Molecular Weight; D009119:Muscle Contraction / Q000187:drug effects; D009124:Muscle Proteins / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents
D009124:Muscle Proteins; D010446:Peptide Fragments; D014665:Vasodilator Agents; D009320:Atrial Natriuretic Factor; D003488:Cyanogen Bromide