Document Detail


Adenovirus-mediated human prostasin gene delivery is linked to increased aldosterone production and hypertension in rats.
MedLine Citation:
PMID:  12626364     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prostasin has been demonstrated to be an activator of epithelial sodium channels in cultured renal and bronchial epithelial cells. In this study, we evaluated the effects of adenovirus-mediated gene transfer of human prostasin on blood pressure regulation and sodium reabsorption in Wistar rats. Expression of human prostasin mRNA was identified in rat adrenal gland, liver, kidney, heart, lung, and aorta, and immunoreactive human prostasin was detected in the circulation and urine of rats receiving prostasin gene transfer. A single injection of adenovirus carrying the prostasin gene caused prolonged increases in blood pressure for 3-4 wk. Blood pressure increase was accompanied by elevated plasma aldosterone levels and reduced plasma renin activity. The increase in blood pressure and plasma aldosterone levels as well as the reduction of plasma renin activity correlated with the expression of human prostasin transgene. Elevated plasma aldosterone levels were detected at 3 days after gene transfer before the development of hypertension, indicating that stimulation of mineralocorticoid production is the primary target of prostasin. Prostasin gene transfer significantly reduced urinary K(+) excretion but increased urinary Na(+) and kallikrein excretion. Elevated renal kallikrein levels promote natriuresis, which may lead to sodium escape and prevent further increases of blood pressure after prostasin gene transfer. In summary, these results suggest that prostasin participates in blood pressure and electrolyte homeostasis by regulating the renin-angiotensin-aldosterone and kallikrein-kinin systems.
Authors:
Cindy Wang; Julie Chao; Lee Chao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2002-12-19
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  284     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-03-10     Completed Date:  2003-04-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1031-6     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425-2211, USA. wangxi@musc.edu
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics*
Aldosterone / blood,  metabolism*
Animals
Blood Pressure
Disease Models, Animal
Female
Gene Expression
Genetic Vectors / genetics
Humans
Hypertension / blood,  genetics,  metabolism*,  urine
Male
Potassium / urine
RNA, Messenger / genetics,  metabolism
Rats
Rats, Wistar
Serine Endopeptidases / genetics*,  metabolism*
Time Factors
Water-Electrolyte Balance
Grant Support
ID/Acronym/Agency:
HL-29397/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 52-39-1/Aldosterone; 7440-09-7/Potassium; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/prostasin

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


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