Type-C natriuretic peptide prevents development of experimental atherosclerosis in rabbits

1. We investigated the effect of local administration of type-C natriuretic peptide (CNP) on the endothelial dysfunction and development of an atheroma-like neointima induced by a peri-arterial collar in rabbits. 2. Peri-arterial collars were placed on both common carotid arteries allowing local treatment of the collared region with either CNP (10 μmol/L) or saline. After 7 days, uncollared (control) and collared sections were taken from both arteries for pharmacological and morphological analysis. 3. Application of the collar markedly attenuated (P < 0.05) endothelium- dependent vasorelaxation induced by acetylcholine (ACh); inhibition of 5- hydroxytryptamine contraction was 80 ± 5% in control sections compared with 44 ± 4% in collared sections from the same arteries. Local infusion of CNP (10 μmol/L) into the collar restored ACh-induced vasorelaxation (74 ± 3% from collared arteries + CNP vs 77 ± 2% from control sections from the same arteries). 4. Type-C natriuretic peptide treatment also reduced (P < 0.05) intimal thickening compared with contralateral collared arteries (intima/media ratio 0.06 ± 0.01 vs 0.16 ± 0.01). 5. These results provide evidence that locally administered CNP is effective in preventing the endothelial dysfunction and development of a neointima in this model.