Document Detail


Kallikrein gene therapy in newborn and adult hypertensive rats.
MedLine Citation:
PMID:  9276159     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The tissue kallikrein-kinin system has been postulated to play an important role in blood pressure regulation. Kallikreins are serine proteinases that release potent vasodilating kinin peptides from precursor kininogens by limited proteolysis. Our recent studies show that systemic delivery of the human tissue kallikrein gene into adult spontaneously hypertensive rats (SHR) results in a sustained reduction of blood pressure for several weeks. The goal of this study is to evaluate whether early delivery of the kallikrein gene into newborn SHR could exert a suppressive effect on blood pressure phenotype during rat growth and development. A human tissue kallikrein cDNA construct, under the control of cytomegalovirus promoter (CMV-cHK), or vector DNA was injected subcutaneously into the necks of 2-day-old SHR. Blood pressures were monitored biweekly from 3 to 19 weeks by the tail-cuff method. A single injection of the human kallikrein cDNA construct caused a significant reduction of blood pressure (n = 6, p < 0.001) from 11 to 17 weeks after injection compared with control rats receiving vector DNA. Intravenous delivery of the human tissue kallikrein gene into adult SHR produced blood pressure lowering effects (n = 6, p < 0.001) that lasted for 6 weeks in male but not in female rats. The expression of human tissue kallikrein in rats was identified by reverse transcription polymerase chain reaction followed by Southern blot analysis and an ELISA specific for human tissue kallikrein. Kallikrein gene delivery did not cause any changes in body weight, urine volume, or water intake in the experimental animals compared with the control group. No antibodies to either human tissue kallikrein or its DNA were detected in rat sera 19 weeks postinjection. These results show that delivery of the kallikrein gene at an early stage of life has a protective effect against development of hypertension in adult SHR and that gender differences could be a factor in kallikrein gene therapy for the treatment of hypertensive disorders.
Authors:
J Chao; Z Yang; L Jin; K F Lin; L Chao
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  75     ISSN:  0008-4212     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-10-27     Completed Date:  1997-10-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  CANADA    
Other Details:
Languages:  eng     Pagination:  750-6     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425-2211, USA.
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology
Animals
Animals, Newborn
DNA, Complementary / administration & dosage*,  genetics,  metabolism
Female
Gene Therapy*
Humans
Hypertension / therapy*
Injections, Subcutaneous
Kallikreins / biosynthesis,  genetics,  physiology*
Male
Pregnancy
RNA, Messenger / metabolism
Rats
Rats, Inbred SHR
Sex Factors
Grant Support
ID/Acronym/Agency:
HL 29397/HL/NHLBI NIH HHS; HL 56686/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/RNA, Messenger; EC 3.4.21.-/Kallikreins

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


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