title: Effects of atrial and brain natriuretic peptides on lysophosphatidylcholine-mediated endothelial dysfunction.
abstract: 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.
authors.affiliation: Department of Cardiology, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: T
authors.initials: T
authors.lastname: Murohara
authors.forename: K
authors.initials: K
authors.lastname: Kugiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Ota
authors.forename: H
authors.initials: H
authors.lastname: Doi
authors.forename: N
authors.initials: N
authors.lastname: Ogata
authors.forename: M
authors.initials: M
authors.lastname: Ohgushi
authors.forename: H
authors.initials: H
authors.lastname: Yasue
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002417:Cattle; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D014652:Vascular Diseases / Q000503:physiopathology*
chemical_list: D008244:Lysophosphatidylcholines; D009566:Nitrates; D009573:Nitrites; D020097:Natriuretic Peptide, Brain; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D015237:Dinoprost; D011493:Protein Kinase C