TY - JOUR
T1 - Enhanced Endothelium-Dependent Relaxations After Gene Transfer of Recombinant Endothelial Nitric Oxide Synthase to Rabbit Carotid Arteries
AU - Kullo, Iftikhar J.
AU - Mozes, Geza
AU - Schwartz, Robert S.
AU - Gloviczki, Peter
AU - Tsutsui, Masato
AU - Katusic, Zvonimir S.
AU - O'Brien, Timothy
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1997/9
Y1 - 1997/9
N2 - We tested the effects of overexpression of the endothelial nitric oxide synthase (eNOS) gene in the normal arterial wall by adenoviral-mediated gene transfer. Rabbit carotid arteries were surgically isolated and exposed to adenoviral vectors encoding eNOS (AdeNOS) or beta-galactosidase (Ad beta Gal) on the contralateral side. Vector solutions at a concentration of 1 x 10 plaque forming units/mL were instilled for 20 minutes before restoration of flow. Arteries were harvested 4 days later for immunostaining, measurement of cGMP, and vasomotor studies. Endothelium-specific gene transfer was confirmed by staining for beta-galactosidase in the Ad beta Gal arteries. Immunostaining of en face endothelial cell imprints from AdeNOS-transduced arteries with a monoclonal antibody to eNOS showed increased immunoreactivity. Basal cGMP levels were significantly greater in the AdeNOS-transduced arteries (18.4 +/- 4.6 versus 4.2 +/- 0.5 pmol/mg protein; P < .05). Contractions to phenylephrine were significantly reduced in the AdeNOS-transduced arteries (area under curve, 106 +/- 5 versus 119 +/- 7; P < .05), but in the presence of the eNOS inhibitor, NG -monomethyl-L-arginine (L-NMMA, 3 x 10-4 mol/L), there was no difference between the two (area under curve, 148 +/- 5 versus 153 +/- 6; P = NS). Relaxations to acetylcholine obtained during submaximal contractions to phenylephrine were significantly enhanced in the AdeNOS-transduced arteries (EC50, 7.45 +/- 0.05 versus 7.23 +/- 0.03; P < .05). We conclude that overexpression of eNOS in the endothelium results in diminished contractile responses, as well as enhanced endothelium-dependent relaxations. These findings imply a possible role for vascular eNOS gene transfer in the treatment of vasospasm and endothelial dysfunction. (Hypertension. 1997;30[part 1]:314-320.).
AB - We tested the effects of overexpression of the endothelial nitric oxide synthase (eNOS) gene in the normal arterial wall by adenoviral-mediated gene transfer. Rabbit carotid arteries were surgically isolated and exposed to adenoviral vectors encoding eNOS (AdeNOS) or beta-galactosidase (Ad beta Gal) on the contralateral side. Vector solutions at a concentration of 1 x 10 plaque forming units/mL were instilled for 20 minutes before restoration of flow. Arteries were harvested 4 days later for immunostaining, measurement of cGMP, and vasomotor studies. Endothelium-specific gene transfer was confirmed by staining for beta-galactosidase in the Ad beta Gal arteries. Immunostaining of en face endothelial cell imprints from AdeNOS-transduced arteries with a monoclonal antibody to eNOS showed increased immunoreactivity. Basal cGMP levels were significantly greater in the AdeNOS-transduced arteries (18.4 +/- 4.6 versus 4.2 +/- 0.5 pmol/mg protein; P < .05). Contractions to phenylephrine were significantly reduced in the AdeNOS-transduced arteries (area under curve, 106 +/- 5 versus 119 +/- 7; P < .05), but in the presence of the eNOS inhibitor, NG -monomethyl-L-arginine (L-NMMA, 3 x 10-4 mol/L), there was no difference between the two (area under curve, 148 +/- 5 versus 153 +/- 6; P = NS). Relaxations to acetylcholine obtained during submaximal contractions to phenylephrine were significantly enhanced in the AdeNOS-transduced arteries (EC50, 7.45 +/- 0.05 versus 7.23 +/- 0.03; P < .05). We conclude that overexpression of eNOS in the endothelium results in diminished contractile responses, as well as enhanced endothelium-dependent relaxations. These findings imply a possible role for vascular eNOS gene transfer in the treatment of vasospasm and endothelial dysfunction. (Hypertension. 1997;30[part 1]:314-320.).
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U2 - 10.1161/01.HYP.30.3.314
DO - 10.1161/01.HYP.30.3.314
M3 - Article
C2 - 9314410
AN - SCOPUS:0030754269
SN - 0194-911X
VL - 30
SP - 314
EP - 320
JO - Hypertension
JF - Hypertension
IS - 3
ER -