Nitric oxide modulates endotoxin-induced platelet-endothelial cell adhesion in intestinal venules

被引:46
作者
Cerwinka, WH [1 ]
Cooper, D [1 ]
Krieglstein, CF [1 ]
Feelisch, M [1 ]
Granger, DN [1 ]
机构
[1] Louisiana State Univ, Dept Mol & Cellular Physiol, Hlth Sci Ctr, Shreveport, LA 71130 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2002年 / 282卷 / 03期
关键词
endotoxemia; nitric oxide synthase; soluble guanylate cyclase; postcapillary venules;
D O I
10.1152/ajpheart.00391.2001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Although platelets have been implicated in the pathogenesis of vascular diseases, little is known about factors that regulate interactions between platelets and the vessel wall under physiological conditions. The objectives of this study were to 1) define the contribution of nitric oxide (NO) to endotoxin (lipopolysaccharide, LPS)-induced platelet-endothelial cell (P/E) adhesion in murine intestinal venules and 2) determine whether the antiadhesive action of NO is mediated by soluble guanylate cyclase (sGC). Adhesive interactions between platelets and endothelial cells were monitored by intravital microscopy. LPS administration into control wild-type mice (WT) resulted in a >15-fold increase in P/E adhesion. Similar responses were observed using endothelial NO synthase (eNOS)-deficient platelets. However, treatment with the NO donor diethylenetriamine-nitric oxide (DETA-NO) attenuated the P/E adhesion response to LPS, whereas the NO synthase inhibitor N-G-nitro-L-arginine methyl ester or eNOS deficiency resulted in an exacerbation. P/E adhesion response did not differ between LPS-treated WT and inducible NOS-deficient mice. Inhibition of sGC abolished the attenuating effects of DETA-NO, whereas the sGC activator 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) reduced LPS-induced P/E adhesion. These findings indicate that 1) eNOS-derived NO attenuates endotoxin-induced P/E adhesion and 2) sGC is responsible for the antiadhesive action of NO.
引用
收藏
页码:H1111 / H1117
页数:7
相关论文
共 27 条
  • [1] Platelets adhere to and translocate on von Willebrand factor presented by endothelium in simulated veins
    André, P
    Denis, CV
    Ware, J
    Saffaripour, S
    Hynes, RO
    Ruggeri, ZM
    Wagner, DD
    [J]. BLOOD, 2000, 96 (10) : 3322 - 3328
  • [2] ANTIPLATELET EFFECTS OF ENDOTHELIUM-DERIVED RELAXING FACTOR AND NITRIC-OXIDE DONORS
    BASSENGE, E
    [J]. EUROPEAN HEART JOURNAL, 1991, 12 : 12 - 15
  • [3] Battinelli EM, 2000, CONTEMP CARDIOL, P123
  • [4] N(G)-NITRO L-ARGININE METHYL-ESTER AND OTHER ALKYL ESTERS OF ARGININE ARE MUSCARINIC RECEPTOR ANTAGONISTS
    BUXTON, ILO
    CHEEK, DJ
    ECKMAN, D
    WESTFALL, DP
    SANDERS, KM
    KEEF, KD
    [J]. CIRCULATION RESEARCH, 1993, 72 (02) : 387 - 395
  • [5] Heterogeneity of expression of E- and P-selectins in vivo
    Eppihimer, MJ
    Wolitzky, B
    Anderson, DC
    Labow, MA
    Granger, DN
    [J]. CIRCULATION RESEARCH, 1996, 79 (03) : 560 - 569
  • [6] Platelet-endothelial interactions in inflamed mesenteric venules
    Frenette, PS
    Moyna, C
    Hartwell, DW
    Lowe, JB
    Hynes, RO
    Wagner, DD
    [J]. BLOOD, 1998, 91 (04) : 1318 - 1324
  • [7] P-selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo
    Frenette, PS
    Denis, CV
    Weiss, L
    Jurk, K
    Subbarao, S
    Kehrel, B
    Hartwig, JH
    Vestweber, D
    Wagner, DD
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (08) : 1413 - 1422
  • [8] PLATELETS ROLL ON STIMULATED ENDOTHELIUM IN-VIVO - AN INTERACTION MEDIATED BY ENDOTHELIAL P-SELECTIN
    FRENETTE, PS
    JOHNSON, RC
    HYNES, RO
    WAGNER, DD
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) : 7450 - 7454
  • [9] Vitronectin receptor (alpha(nu)beta(3)) mediates platelet adhesion to the luminal aspect of endothelial cells - Implications for reperfusion in acute myocardial infarction
    Gawaz, M
    Neumann, FJ
    Dickfeld, T
    Reininger, A
    Adelsberger, H
    Gebhardt, A
    Schomig, A
    [J]. CIRCULATION, 1997, 96 (06) : 1809 - 1818
  • [10] An open-label dose escalation study of the nitric oxide synthase inhibitor, NG-methyI-L-arginine hydrochloride (546C88), in patients with septic shock
    Grover, R
    Zaccardelli, D
    Colice, G
    Guntupalli, K
    Watson, D
    Vincent, JL
    [J]. CRITICAL CARE MEDICINE, 1999, 27 (05) : 913 - 922