Document Detail


Adrenomedullin gene delivery reduces blood pressure in spontaneously hypertensive rats.
MedLine Citation:
PMID:  9453262     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adrenomedullin (ADM) is a potent vasoactive peptide. In this study, we explored the effects of a continuous supply of ADM by somatic gene delivery on spontaneously hypertensive rats (SHR). DNA constructs containing the human ADM cDNA fused to either the cytomegalovirus promoter (CMV-cADM) or Rous Sarcoma virus 3'-long terminal repeat (RSV-cADM) were intravenously injected into SHR through the tail vein. Expression of human ADM in SHR was identified in the kidney, adrenal gland, heart, and lung by radioimmunoassay and reverse transcription-polymerase chain reaction followed by Southern blot analysis. A single injection of ADM plasmid DNA in young adult SHR (7 wk old) caused a significant reduction in systolic blood pressure for up to 5 wk (p < 0.05). A second injection of CMV-cADM 5 wk after the first delivery resulted in a further reduction in blood pressure for another 3 wk (p < 0.001). A maximal blood pressure reduction of 22 mmHg in SHR was observed 7 wk after injection of CMV-cADM plasmid DNA (185 +/- 1.7 mmHg, n = 6, p < 0.001), and a reduction of 15 mmHg was observed after injection of RSV-cADM (192 +/- 2.7 mmHg, n = 6, p < 0.001), as compared with control rats given vector DNA (207 +/- 2.4 mmHg, n = 6). Similarly, injection of CMV-cADM plasmid DNA in adult SHR (10 wk old) resulted in a significant reduction in blood pressure for up to 6 wk. Antibodies to either human ADM or its plasmid DNA were not detected in rat sera after the second injection. These studies indicate that intravenous injection of the human ADM gene in hypertensive rats results in expression of the foreign gene and induces a long-lasting reduction in blood pressure.
Authors:
J Chao; L Jin; K F Lin; L Chao
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension research : official journal of the Japanese Society of Hypertension     Volume:  20     ISSN:  0916-9636     ISO Abbreviation:  Hypertens. Res.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-03-12     Completed Date:  1998-03-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9307690     Medline TA:  Hypertens Res     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  269-77     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:
Adrenomedullin
Animals
Antibody Formation
Avian Sarcoma Viruses / genetics
Blood Pressure / drug effects*,  genetics
Cytomegalovirus / genetics
DNA, Complementary / genetics
DNA, Recombinant / adverse effects,  genetics,  therapeutic use
Gene Expression
Gene Therapy*
Humans
Hypertension / therapy*
Hypotension / etiology
Injections, Intravenous
Kidney / cytology,  embryology,  enzymology
Lung / enzymology
Peptides / genetics*
RNA, Messenger / analysis,  genetics
Rats
Rats, Inbred SHR
Spleen / enzymology
Tissue Distribution
Transfection
beta-Galactosidase / metabolism
Grant Support
ID/Acronym/Agency:
HL 29397/HL/NHLBI NIH HHS; HL 44083/HL/NHLBI NIH HHS; HL 56686/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/DNA, Recombinant; 0/Peptides; 0/RNA, Messenger; 148498-78-6/Adrenomedullin; EC 3.2.1.23/beta-Galactosidase
Comments/Corrections
Comment In:
NIH Guide Grants Contracts. 2001 Jun 27;:NOT-OD-01-047   [PMID:  12449951 ]
Erratum In:
Hypertens Res 1999 Sep;22(3):229
Hypertens Res 2001 Sep;24(5):611

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


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