NO-dependent vasorelaxation is impaired after gene transfer of inducible NO-synthase

Citation
Ca. Gunnett et al., NO-dependent vasorelaxation is impaired after gene transfer of inducible NO-synthase, ART THROM V, 21(8), 2001, pp. 1281-1287
Citations number
53
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
10795642 → ACNP
Volume
21
Issue
8
Year of publication
2001
Pages
1281 - 1287
Database
ISI
SICI code
1079-5642(200108)21:8<1281:NVIIAG>2.0.ZU;2-A
Abstract
Proinflammatory stimuli produce expression of inducible NO-synthase (iNOS) within blood vessels and are associated with impaired endothelium-dependent relaxation. Gene transfer of iNOS was used to test the hypothesis that exp ression of iNOS in blood vessels produces impairment of NO-dependent relaxa tion as well as contraction. An adenoviral vector containing cDNA for murin e iNOS, AdCMViNOS, and a control virus, AdCMVBgIII, were used for gene tran sfer to rabbit carotid arteries in vitro and in vivo. After gene transfer o f iNOS in vitro, contractile responses to KCl, phenylephrine, and U46619 we re impaired. Relaxation in response to acetylcholine, ADP, A23187, and nitr oprusside was also impaired. For example, maximum relaxation of vessels to acetylcholine (10 mu mol/L) was 78 +/-4% (mean +/- SE) after AdBgIII (10(10 .5) plaque-forming units) and 34 +/-5% after AdiNOS (10(10.5) plaque-formin g units, P <0.05). NO-independent relaxation in response to 8-bromo-cGMP an d papaverine was not impaired after AdiNOS. Contraction and relaxation were improved in carotid arteries expressing iNOS by aminoguanidine and L-N-imi noethyl lysine, inhibitors of iNOS. After intraluminal gene transfer of iNO S in vivo, contraction of vessels in vitro was normal, but responses to ace tylcholine were impaired. In summary, the major finding is that NO-dependen t relaxation is impaired in arteries after gene transfer of iNOS in vitro a nd in vivo. Thus, expression of iNOS per se impairs NO-dependent relaxation .