Vasomotor dysfunction early after exposure of normal rabbit arteries to an adenoviral vector

被引:35
作者
Lafont, A
Loirand, G
Pacaud, P
Vilde, F
Lemarchand, P
Escande, D
机构
[1] HOP G&R LAENNEC, INSERM, CJF 9601, LAB PHYSIOPATHOL & PHARMACOL CELLULAIRES & MOL, F-44035 NANTES, FRANCE
[2] HOP BOUCICAULT, PARIS, FRANCE
[3] IPMC, CNRS, UPR 411, SOPHIA ANTIPOLIS, FRANCE
[4] FAC MED NECKER ENFANTS MALAD, INSERM, U25, PARIS, FRANCE
关键词
D O I
10.1089/hum.1997.8.9-1033
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
We aimed to investigate whether infection of normal rabbit arteries with a recombinant adenovirus vector would result per se in alterations in contractile and endothelial functions, In one group of rabbits, right or left femoral and ear artery segments were injected in vivo with a replication-deficient adenoviral vector expressing a beta-galactosidase (beta-Gal) reporter gene (4 x 10(10) pfu/ml) to demonstrate efficient gene transfer. Contralateral arteries were injected with the same concentration of a recombinant adenoviral vector carrying no transgene (Ad.MLPnull). In another group of animals, Ad.MLPnull was injected into the lumen of femoral and ear artery segments, The contralateral arteries were used as controls with the injection of vehicle alone, Histochemical assessment of gene transfer using beta-Gal activity (group 1) or in vitro contractility and endothelial function (group 2) was performed 3 days after adenoviral infection, Gene transfer was efficient and reproducible in the endothelium and was associated with the presence of inflammatory cells in the media, In Ad.MLPnull-injected arteries, in vitro contractile response of femoral artery rings to either KCl 60 mM or phenylephrine (10 mu M) was reduced to 10.5 +/- 2.3% (n = 14; p < 0.001) and 8.8 +/- 2.0% (n = 7; p < 0.001) of the control values, respectively, Furthermore, in arteries injected with Ad.MLPnull, the endothelium-dependent relaxation produced by acetylcholine (10 mu M) was virtually abolished, Similarly, the relaxant effects of the alpha(2)-adrenoreceptor agonist UK14304 (1 mu M) or the Ca2+ ionophore A23187 (1 mu M) were also abolished, By contrast, sodium nitroprusside (10 mu M) was still able to relax adenovirus-infected arteries, We conclude that infection with a recombinant adenoviral vector can induce early severe vasomotor alterations in both contractile function and endothelium-mediated relaxation off normal rabbit arteries.
引用
收藏
页码:1033 / 1040
页数:8
相关论文
共 35 条
[1]   INTERLEUKIN-1 INDUCES PROLONGED L-ARGININE-DEPENDENT CYCLIC GUANOSINE-MONOPHOSPHATE AND NITRITE PRODUCTION IN RAT VASCULAR SMOOTH-MUSCLE CELLS [J].
BEASLEY, D ;
SCHWARTZ, JH ;
BRENNER, BM .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (02) :602-608
[2]   INDUCTION OF NITRIC-OXIDE SYNTHASE BY CYTOKINES IN VASCULAR SMOOTH-MUSCLE CELLS [J].
BUSSE, R ;
MULSCH, A .
FEBS LETTERS, 1990, 275 (1-2) :87-90
[3]  
DANNENBERG AM, 1981, METHODS STUDYING MON, P375
[4]   Supernatant rescue assay vs polymerase chain reaction for detection of wild type adenovirus-contaminating recombinant adenovirus stocks [J].
Dion, LD ;
Fang, J ;
Garver, RI .
JOURNAL OF VIROLOGICAL METHODS, 1996, 56 (01) :99-107
[5]   EVALUATION OF THE RESPIRATORY EPITHELIUM OF NORMALS AND INDIVIDUALS WITH CYSTIC-FIBROSIS FOR THE PRESENCE OF ADENOVIRUS E1A SEQUENCES RELEVANT TO THE USE OF E1A(-) ADENOVIRUS VECTORS FOR GENE-THERAPY FOR THE RESPIRATORY MANIFESTATIONS OF CYSTIC-FIBROSIS [J].
EISSA, NT ;
CHU, CS ;
DANEL, C ;
CRYSTAL, RG .
HUMAN GENE THERAPY, 1994, 5 (09) :1105-1114
[6]   PROTECTION OF HUMAN ENDOTHELIAL-CELLS FROM OXIDANT INJURY BY ADENOVIRUS-MEDIATED TRANSFER OF THE HUMAN CATALASE CDNA [J].
ERZURUM, SC ;
LEMARCHAND, P ;
ROSENFELD, MA ;
YOO, JH ;
CRYSTAL, RG .
NUCLEIC ACIDS RESEARCH, 1993, 21 (07) :1607-1612
[7]   Recombinant adenovirus deleted of all viral genes for gene therapy of cystic fibrosis [J].
Fisher, KJ ;
Choi, H ;
Burda, J ;
Chen, SJ ;
Wilson, JM .
VIROLOGY, 1996, 217 (01) :11-22
[8]  
FLAVAHAN NA, 1986, J PHARMACOL EXP THER, V239, P784
[9]  
GRAHAM FL, 1992, VACCINES NEW APPROAC, P363
[10]   EFFICIENT AND SELECTIVE ADENOVIRUS-MEDIATED GENE-TRANSFER INTO VASCULAR NEOINTIMA [J].
GUZMAN, PJ ;
LEMARCHAND, P ;
CRYSTAL, RG ;
EPSTEIN, SE ;
FINKEL, T .
CIRCULATION, 1993, 88 (06) :2838-2848