Effects of atrial and brain natriuretic peptides on lysophosphatidylcholine-mediated endothelial dysfunction.

Lysophosphatidylcholine (LPC), a major atherogenic lysophospholipid contained in oxidized low-density lipoprotein (ox-LDL), induces endothelial dysfunction. Recent studies showed that natriuretic peptides (NPs) have antiatherogenic properties by inhibiting vascular smooth-muscle cell proliferation, but their effects on endothelial cells are little known. We examined whether atrial and brain NPs (ANP and BNP) have a protecting action against LPC-induced endothelial dysfunction. LPC (10 microM) significantly inhibited thrombin (0.001-1 U/ml)-induced endothelium-dependent relaxation without affecting endothelium-independent relaxation to sodium nitroprusside in isolated porcine coronary arteries. The impaired endothelium-dependent relaxation induced by LPC was prevented by treatment with ANP or BNP (i microM). In cultured bovine aortic endothelial cells (BAECs), LPC (10 microM) significantly attenuated bradykinin (1 microM)-stimulated nitric oxide (NO) release; however, this was prevented by ANP and BNP. Because LPC-induced endothelial dysfunction has been shown to be mediated at least in part by activation of the protein kinase C (PKC)-dependent signaling pathway, we also examined the effects of ANP and BNP on LPC-induced modulation of PKC activities in BAECs. LPC (10 microM) significantly stimulated PKC activity in BAECs. However, ANP or BNP significantly inhibited LPC (10 microM)-induced PKC activation. In conclusion, ANP and BNP protected endothelial cells from LPC-induced dysfunction in both isolated coronary arteries and cultured ECs. The mechanism appears to be at least in part related to the inhibition of LPC-induced PKC activation by NPs. These new actions of ANP and BNP against lysolipid-induced endothelial cytotoxicity may partly account for antiatherogenic properties of NPs.