Document Detail


Prolonged reduction of high blood pressure with human nitric oxide synthase gene delivery.
MedLine Citation:
PMID:  9314409     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endothelium-derived nitric oxide (NO) in peripheral vessels has been shown to modulate vascular resistance and blood pressure. We explored the effect of a continuous supply of human endothelial NO synthase (eNOS) on the blood pressure of spontaneously hypertensive rats (SHR) by somatic gene delivery. A DNA construct containing the human eNOS gene fused to the cytomegalovirus promoter/enhancer was injected into SHR through the tail vein. A single injection of the naked eNOS plasmid DNA caused a significant reduction of systemic blood pressure for 5 to 6 weeks in SHR, and the effect continued for up to 10 to 12 weeks after a second injection. The differences were significant from 2 to 12 weeks postinjections (n=6, P<.01). In a separate experiment, L-arginine, the substrate of eNOS, was supplied in drinking water at a concentration of 7.5 g/L for 11 weeks after eNOS gene delivery. A maximal blood pressure reduction of 21 mm Hg in SHR was observed with eNOS DNA compared with that of control SHR injected with vector DNA (181.9+/-1.46 versus 202.7+/-2.79 mm Hg, mean+/-SEM, n=6, P<.01). Human eNOS gene delivery induces significant increases in urinary and aortic cGMP levels and urinary and serum nitrite/nitrate content (P<.05), while no significant differences in body weight, heart rate, water intake, food consumption, or urine excretion were observed. These results indicate that somatic delivery of the human eNOS gene induces a prolonged reduction of high blood pressure and raises the potential of using eNOS gene therapy for hypertension and cardiovascular diseases.
Authors:
K F Lin; L Chao; J Chao
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  30     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-10-30     Completed Date:  1997-10-30     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  307-13     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginine
Blood Pressure / drug effects
Cattle
Cell Line
Cyclic GMP / metabolism
Cytomegalovirus / genetics
DNA / genetics
Endothelium, Vascular / cytology,  metabolism
Gene Therapy*
Humans
Hypertension / chemically induced,  physiopathology,  therapy*
Male
Nitric Oxide Synthase / genetics*,  therapeutic use
Promoter Regions, Genetic / genetics
Pulmonary Artery / cytology,  metabolism
Rats
Rats, Inbred SHR / physiology
Time Factors
Transfection
Grant Support
ID/Acronym/Agency:
HL 29397/HL/NHLBI NIH HHS; HL 44083/HL/NHLBI NIH HHS; HL 56683/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
74-79-3/Arginine; 7665-99-8/Cyclic GMP; 9007-49-2/DNA; EC 1.14.13.39/Nitric Oxide Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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