Dendroaspis natriuretic peptide is degraded by a metalloproteinase in the rat kidney

Our previous study demonstrated that the concentration of dendroaspis natriuretic peptide (DNP) was markedly higher than that of atrial NP (ANP) in rabbit plasma, indicating that DNP has a different metabolic rate from other NPs. Therefore, the metabolic characteristics of DNP in mammals require further analysis. The stabilities of NPs were determined by incubating I-125-labeled ANP, brain NP (BNP), C-type NP (CNP) and DNP at 37 degrees C for 1, 2 and 4 h, and analyzing their profiles by reversed-phase high-performance liquid chromatography. I-125-labeled ANP, BNP and CNP were quickly degraded in rat plasma, while I-125-labeled DNP was stable for 4 h. The relative stability of the peptides following incubation in rat plasma followed the rank order of: DNP>>>ANPBNP>>CNP. Organs were also examined for the degradation of DNP, including the spleen, kidney, liver, heart and lung. The physiological target organ for the degradation of DNP was observed to be the kidney. Furthermore, degradation of DNP in the kidney was attenuated by phenanthroline, a metalloproteinase inhibitor. Therefore, these results indicate that DNP has a longer stability in plasma and that it may have strong therapeutic applications in cardiac disease.