NO mediates the effect of the synthetic natriuretic peptide NPCdc on kidney and aorta in nephrectomised rats

Abstract

NPCdc is a synthetic natriuretic peptide that was originally derived from another peptide, the NP2_Casca, isolated from Crotalus durissus cascavella venom. These molecules share 70% structural homology with natriuretic peptides obtained from different species, including humans. NP2_Casca induces vasorelaxation and increases nitric oxide levels independently of natriuretic peptide receptors A and B. This study aimed to investigate whether NPCdc-induced hypotension in control rats and rats with a reduced kidney mass is associated with effects on the glomerular filtration rate, NADPH oxidase activity and components downstream of natriuretic peptide receptor C (NPR-C). Anaesthetized Wistar rats that were subjected to a sham operation and 5/6 nephrectomy (5/6Nx) were infused with saline (vehicle) or NPCdc (7.5 μg/kg/min) for 70 min. The NPCdc treatment decreased the mean arterial pressure and NADPH oxidase activity while simultaneously increasing the glomerular filtration rate, fractional Na+ excretion and nitric oxide level. After 70 min, the levels of p-AKT Ser−473, p-eNOS Ser−1177, p-nNOS Ser−1417 and p-iNOSTyr−151 were not affected. However, p-ERK1/2 Thr−202/Tyr−204 levels were altered. Thus, nitric oxide and components of NPR-C signalling mediate the effects of NPCdc. The results suggest a potential therapeutic application of this peptide for cardiorenal syndrome.