The influence of chylomicron remnants on endothelial cell function in the isolated perfused rat aorta

被引:52
作者
Grieve, DJ [1 ]
Avella, MA [1 ]
Elliott, J [1 ]
Botham, KM [1 ]
机构
[1] Univ London Royal Coll Vet Surg, Dept Vet Basic Sci, London NW1 0TU, England
基金
英国医学研究理事会;
关键词
chylomicron remnants; copper oxidation; endothelium-derived relaxing factor; perfusion of the isolated rat aorta;
D O I
10.1016/S0021-9150(98)00078-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
A system for the perfusion of the isolated rat aorta which allowed the study of both the uptake of chylomicron remnants by the artery wall and their effects on endothelial function was developed. Perfusion for 2 h with I-125-labelled native or oxidised (by treatment with copper sulphate) chylomicron remnants showed that small amounts became associated with the artery wall (0.111 +/- 0.034 and 0.216 +/- 0.082 ng protein/mg tissue, respectively). Tests on endothelial function were carried out in vessel rings prepared after perfusion of the aortas in the presence or absence of chylomicron remnants for 2 h. After perfusion of the vessels with oxidised chylomicron remnants, the maximum response to phenylephrine (PE) was significantly increased (from 0.34 +/- 0.06 to 0.51 +/- 0.04 g/mg tissue; P < 0.05), while the maximum % relaxation to carbachol (CCh) was significantly decreased (from 91.6 +/- 2.4 to 71.5 +/- 7.2; P < 0.05) and the response to S-nitroso-N-acetylpenicillimine (SNAP) was unaffected. Perfusion with native chylomicron remnants showed a tendency to induce similar effects, although the changes observed did not reach statistical significance. As the lipoproteins were not present in the solution bathing the vessel rings during these tests, these effects can be attributed to perfusion of the aortas with chylomicron remnants, despite only small quantities being associated with the artery wall. The results suggest that oxidised chylomicron remnants influence vascular endothelial function by interfering with the L-arginine-nitric oxide (NO) pathway. The observed potentiation of contraction to PE may be due to inhibition of the basal release of NO or to the release of contractile factors. These findings support a role for dietary lipoproteins in the modulation of endothelial cell function which occurs in the pathogenesis of atherosclerosis. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:273 / 281
页数:9
相关论文
共 42 条
[1]   LOW-DENSITY LIPOPROTEINS INHIBIT ENDOTHELIUM-DEPENDENT RELAXATION IN RABBIT AORTA [J].
ANDREWS, HE ;
BRUCKDORFER, KR ;
DUNN, RC ;
JACOBS, M .
NATURE, 1987, 327 (6119) :237-239
[2]   Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene [J].
Benlian, P ;
DeGennes, JL ;
Foubert, L ;
Zhang, HF ;
Gagne, SE ;
Hayden, M .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (12) :848-854
[3]   OXIDIZED LOW-DENSITY LIPOPROTEINS INDUCE MESSENGER-RNA EXPRESSION AND RELEASE OF ENDOTHELIN FROM HUMAN AND PORCINE ENDOTHELIUM [J].
BOULANGER, CM ;
TANNER, FC ;
BEA, ML ;
HAHN, AWA ;
WERNER, A ;
LUSCHER, TF .
CIRCULATION RESEARCH, 1992, 70 (06) :1191-1197
[4]   INFLUENCE OF THE VASCULAR ENDOTHELIUM ON AGONIST-INDUCED CONTRACTIONS AND RELAXATIONS IN RAT AORTA [J].
BULLOCK, GR ;
TAYLOR, SG ;
WESTON, AH .
BRITISH JOURNAL OF PHARMACOLOGY, 1986, 89 (04) :819-830
[5]   EFFECT OF INCREASING DOSES OF ANGIOTENSIN-II INFUSED INTO NORMAL AND HYPERTENSIVE WISTAR RATS ON LOW-DENSITY-LIPOPROTEIN AND FIBRINOGEN UPTAKE BY AORTIC WALLS [J].
CARDONASANCLEMENTE, LE ;
MEDINA, R ;
BORN, GVR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (08) :3285-3288
[6]  
CORTNER JA, 1987, J LIPID RES, V28, P195
[7]  
Cox DA, 1996, PHARMACOL REV, V48, P3
[8]  
FELDMAN DL, 1984, ARCH PATHOL LAB MED, V108, P817
[9]   EXPERIMENTAL PRODUCTION OF GROSS ATHEROSCLEROSIS IN THE RAT [J].
FILLIOS, LC ;
ANDRUS, SB ;
MANN, GV ;
STARE, FJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1956, 104 (04) :539-&
[10]  
FRAKER PJ, 1978, BIOCHEM BIOPH RES CO, V80, P849, DOI 10.1016/0006-291X(78)91322-0