Cardiovascular and renal effect of CNAAC: An innovatively designed natriuretic peptide

Natriuretic peptides (NPs) have natriuretic, diuretic and vasodilator effects. An innovative natriuretic peptide analogue called CNAAC (a new chimera peptide combining the C-terminus and ring of ANP with the N-terminus of CNP) was designed to determine whether it has any cardiovascular and renal effect. Abdominal aorta of rats were isolated and vascular ring perfusion was employed to compare the vasodilator effect and cGMP excretion effect of CNAAC with natural NPs. Urine volume and urine cGMP levels after intravenous injection of CNAAC and natural NPs were determined. Hemodynamic methods were employed to assess the effect of CNAAC and natural NPs on MAP. CNAAC relaxed abdominal aorta in a dose-dependent manner and was independent of endothelium. The vasodilating effect of CNAAC was significantly attenuated in the presence of NPR-A antibody, GC inhibitor, and KATP inhibitor and was abolished by PKG inhibitor. Abdominal aortic cGMP production increased after incubation with NPs. Urine volume, plasma cGMP, and urine cGMP increased and MAP decreased dramatically after intravenous injection of CNAAC. CNAAC has a potent vasodilating effect, probably by activating K(+) channels via NPR-A/sGC/cGMP pathway. Exogenous administration of CNAAC elicits diuretic and hypotensive effects.