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

Lysophosphatidylcholine (LPC), a major atherogenic lysophospholipid contain ed in oxidized low-density lipoprotein (ox-LDL), induces endothelial dysfun ction. Recent studies showed that natriuretic peptides (NPs) have antiather ogenic properties by inhibiting vascular smooth-muscle cell proliferation, but their effects on endothelial cells are little known. We examined whethe r atrial and brain NPs (ANP and BNP) have a protecting action against LPC-i nduced endothelial dysfunction. LPC (10 mu M) significantly inhibited throm bin (0.001-1 U/ml)-induced endothelium-dependent relaxation without affecti ng endothelium-independent relaxation to sodium nitroprusside in isolated p orcine coronary arteries. The impaired endothelium-dependent relaxation ind uced by LPC was prevented by treatment with ANP or BNP (1 mu M) In cultured bovine aortic endothelial cells (BAECs), LPC (10 mu M) significantly atten uated bradykinin (1 mu M)-stimulated nitric oxide (NO) release; however, th is was prevented by ANP and BNP. Because LPC-induced endothelial dysfunctio n has been shown to be mediated at least in part by activation of the prote in kinase C (PKC)-dependent signaling pathway, wt? also examined the effect s of ANP and BNP on LPC-induced modulation of PKC activities in BAECs. LPC (10 mu M) significantly stimulated PKC activity in BAECs. However, ANP or B NP significantly inhibited LPC (10 mu M)-induced PKC activation. In conclus ion, ANP and BNP protected endothelial cells from LPC-induced dysfunction i n both isolated coronary arteries and cultured ECs. The mechanism appears t o be at least in part related to the inhibition of LPC-induced PKC activati on by NPs. These new actions of ANP and BNP against lysolipid-induced endot helial cytotoxicity may partly account for antiatherogenic propel ties of N Ps.