Document Detail


Lifelong angiotensin-converting enzyme inhibition, pressure natriuresis, and renin-angiotensin system gene expression in transgenic (mRen-2)27 rats.
MedLine Citation:
PMID:  8915971     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The transgenic rat (TGR) (mRen-2)27 is said to have low circulating active renin values in plasma and little or no renin gene expression in the kidney. Nevertheless, intrarenal angiotensin II-related effects appear to be responsible for the rightward shift in pressure-natriuresis curves of TGR. To clarify the role of the intrarenal renin-angiotensin system in modulating TGR pressure-natriuresis, TGR were given lifelong lisinopril by treating TGR and their mothers before conception. Rat and mouse renin, AT1 receptor, and angiotensinogen gene expression in the kidneys were studied with in situ hybridization. Neural and endocrine regulatory differences between TGR and Sprague-Dawley Hannover (SDH) rats were eliminated by renal denervation and infusion of vasopressin, aldosterone, 17-OH corticosterone, and norepinephrine. TGR with lisinopril had blood pressures similar to SDH. In TGR with lisinopril, the pressure-natriuresis curve was shifted leftward but not quite to the values observed in SDH given lisinopril. The histology of lisinopril-treated TGR was indistinguishable from normal SDH. Lisinopril increased rat renin and angiotensinogen gene expression both in SDH and TGR, but it did not influence mouse renin gene expression in TGR. Discontinuing lisinopril increased blood pressure in TGR and shifted the pressure-natriuresis relationship rightward. Thus, the components of the endogenous renin-angiotensin system and the mouse renin transgene were present and expressed in kidneys of TGR. The rat gene components responded to lisinopril as expected, but the mouse renin transgene expression was not influenced. Lisinopril normalized TGR blood pressure; however, a detectable leftward shift in pressure-natriuresis remained. These studies underscore the role of angiotensin-mediated effects of the mouse renin transgene in terms of shifting pressure-natriuresis in TGR.
Authors:
A Lippoldt; V Gross; J Bohlender; U Ganten; F C Luft
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  7     ISSN:  1046-6673     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1997-02-26     Completed Date:  1997-02-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2119-29     Citation Subset:  IM    
Affiliation:
Max Delbrück Center for Molecular Medicine, Virchow Klinikum, Humboldt University of Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Animals
Animals, Genetically Modified / genetics*,  physiology
Blood Pressure / physiology*
Gene Expression*
In Situ Hybridization
Kidney / drug effects,  pathology
Lisinopril / pharmacology
Male
Mice / genetics
Natriuresis / physiology*
Rats
Rats, Sprague-Dawley
Renin / genetics
Renin-Angiotensin System / physiology*
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 83915-83-7/Lisinopril; EC 3.4.23.15/Renin

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


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