Gene transfer of endothelial NO synthase and manganese superoxide dismutase on arterial vascular cell adhesion molecule-1 expression and superoxide production in deoxycorticosterone acetate-salt hypertension.
Enhanced vascular cell adhesion molecule-1 (VCAM-1) expression directly contributes to vascular dysfunction in hypertension. Decreased NO and/or increased superoxide are causative factors for such an event in the vessel wall. The present study was undertaken to determine whether gene transfer of endothelial NO synthase (eNOS) or manganese superoxide dismutase (MnSOD) affects VCAM-1 levels in arteries from hypertensive rats. Isolated carotid and femoral arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats were transduced for 4 hours with adenoviral vectors encoding eNOS, MnSOD, or beta-galactosidase reporter genes. Recombinant eNOS or MnSOD expression was evident morphologically and quantitatively 24 hours after gene transfer. Immunohistochemistry, ELISA, and Western blot techniques were used to determine VCAM-1 expression and levels. In addition, endogenous eNOS and MnSOD and in situ superoxide levels were analyzed by immunoblotting and fluorescence confocal microscopy, respectively. Arterial VCAM-1 expression was significantly higher in DOCA-salt hypertensive rats than in sham-operated rats; this expression was accompanied by decreased MnSOD but unaltered endogenous eNOS levels. VCAM-1 expression was significantly lower in MnSOD- and eNOS-transduced hypertensive arteries, with a concomitant reduction of superoxide level. These results suggest that gene transfer of MnSOD or eNOS suppresses arterial VCAM-1 expression in DOCA-salt hypertension by reducing the superoxide level.
Li
Lixin
L
Department of Pharmacology, Michigan State University, East Lansing 48824-1317, USA.
Crockett
Elahe
E
Wang
Donna H
DH
Galligan
James J
JJ
Fink
Gregory D
GD
Chen
Alex F
AF
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D002339:Carotid Arteries / Q000378:metabolism; D003900:Desoxycorticosterone; D005263:Femoral Artery / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019010:Vascular Cell Adhesion Molecule-1; D013481:Superoxides; D003900:Desoxycorticosterone; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase