Remnant-like particles from subjects who died of coronary artery disease suppress NO synthase activity and attenuate endothelium-dependent vasorelaxation.
BACKGROUND
Plasma levels of remnant-like particles (RLP) is one of the predictive markers for coronary artery disease (CAD), and the inhibition by RLP of endothelium-dependent vasorelaxation has been reported. We attempted to clarify whether or not RLP, which inhibits endothelium-dependent vasorelaxation, affects nitric oxide (NO) production and NO synthase (eNOS) levels in cultured endothelial cells.


METHODS
RLP were obtained from postmortem blood of subjects who died of CAD. Modification by RLP of acetylcholine-induced relaxation of rabbit aorta, and changes in NO production and (eNOS) in cultured bovine endothelial cells were examined.


RESULTS
RLP at 750 and 1500 microg triglyceride/ml inhibited vasorelaxation, and at 5-160 microg triglyceride/ml, concentration-dependently inhibited NO production. However, (eNOS) did not decrease after incubation with RLP.


CONCLUSIONS
Postmortem RLP from subjects who died of CAD do not change the amount of (eNOS), but rather, inhibits its activity and attenuates endothelium-dependent vasorelaxation.
Ohara
Naoki
N
Department of Pharmacology, Food and Drug Safety Center, Hatano Research Institute, Ochiai 729-5, Hadano, Kanagawa, 257-8523, Japan. ohara.n@fdsc.or.jp
Takeichi
Sanae
S
Naito
Yukiko
Y
Nakajima
Yasuhiro
Y
Yukawa
Nobuhiro
N
Nakano
Takamitsu
T
Nakajima
Katsuyuki
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D001344:Autopsy; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood* / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000097:blood*; D017077:Culture Media, Conditioned / Q000737:chemistry; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011817:Rabbits; D014280:Triglycerides / Q000097:blood* / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D017077:Culture Media, Conditioned; D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D009569:Nitric Oxide; D002784:Cholesterol; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine