Definitive role for natriuretic peptide receptor-C in mediating the vasorelaxant activity of C-type natriuretic peptide and endothelium-derived hyperpolarising factor.

摘要: Objective : C-type natriuretic peptide (CNP) has recently been suggested to represent an endothelium-derived hyperpolarising factor (EDHF) in the mammalian resistance vasculature and, as such, important regulation of local blood flow and systemic pressure. Additionally, this shown protect against ischaemia–reperfusion injury inhibits leukocyte platelet activation. Herein, we use a novel, selective receptor-C (NPR-C) antagonist (M372049) highlight pivotal contribution CNP/NPR-C signalling EDHF-dependent vascular tone investigate mechanism(s) underlying release biological activity CNP. Methods In vitro pharmacological investigation was conducted rat (Sprague–Dawley) aorta mesenteric arteries. Relaxant responses CNP, atrial (ANP), nitric oxide donor spermine-NONOate (SPER-NO) endothelium-dependent vasodilator, acetylcholine (ACh) were examined absence presence M372049 or inhibitor cocktails previously block dilatation vasculature. RT-PCR employed characterize expression NPR subtypes vessels studied. Results produced concentration-dependent inhibition vasorelaxant CNP isolated arteries but not aorta; contrast, did affect relaxations ANP SPER-NO either vessel. ouabain alone small, significant combination acted synergistically abolish such responses. A with established inhibitors relaxation revealed that multiple, distinct pathways coordinate bioactivity EDHF vasculature, represents major component. Conclusions These data substantiate fundamental pathway An increased understanding physiological roles (now facilitated by identification NPR-C antagonist) should aid determination (patho)physiological importance might provide rationale for design novel therapeutics.