Nitric oxide modulates natriuretic peptide receptor C expression in aortic vascular smooth muscle cells

Abstract

We have recently shown that cyclic GMP (cGMP) decreased the expression of natriuretic peptide receptor C (NPR‐C) in vascular smooth muscle cells (VSMC). Since cGMP is the second messenger of nitric oxide (NO), the present studies were undertaken to investigate if NO can mimic the effect of cGMP in attenuating the expression and associated Gia‐adenylyl cyclase signaling of NPR‐C in aortic VSMC.Treatment of VSMC with SNAP (100 μM) decreased the expression of NPR‐C, Gia‐2 and Gia‐3 proteins in a time‐dependent manner, as determined by Western Blotting. The maximal inhibition of Gia‐2, Gia‐3 and NPR‐C proteins was between 30–35%. The NO‐induced decreased levels of NPR‐C and Giá proteins at 24 h was also reflected in decreased NPR‐C‐mediated adenylyl cyclase inhibition, as determined by C‐ANP4‐23‐mediated inhibition of adenylyl cyclase. Furthermore, ODQ, an inhibitor of soluble guanylyl cyclase, KT5823, an inhibitor of protein kinase G, and MnTBAP, a scavenger of peroxynitrite, were unable to restore the SNAP‐induced decreased expression of NPR‐C protein to control levels, suggesting that SNAP‐mediated decreased expression of NPR‐C is not through peroxynitrite or cGMP‐dependent mechanism. These results suggest that NO decreases NPR‐C expression and that the NO‐induced decreased expression of NPR‐C is mediated through a cGMP‐independent pathway. (Supported by Canadian Institutes of Health Research)