Document Detail

In vivo expression of angiotensin-(1-7) lowers blood pressure and improves baroreflex function in transgenic (mRen2)27 rats.
MedLine Citation:
PMID:  22526299     Owner:  NLM     Status:  MEDLINE    
Transgenic (mRen2)27 rats are hypertensive with impaired baroreflex sensitivity for control of heart rate compared with Hannover Sprague-Dawley rats. We assessed blood pressure and baroreflex function in male hemizygous (mRen2)27 rats (30-40 weeks of age) instrumented for arterial pressure recordings and receiving into the cisterna magna either an Ang-(1-7) fusion protein or a control fusion protein (CTL-FP). The maximum reduction in mean arterial pressure achieved was -38 ± 7 mm Hg on day 3, accompanied by a 55% enhancement in baroreflex sensitivity in Ang-(1-7) fusion protein-treated rats. Both the high-frequency alpha index (HF-α) and heart rate variability increased, suggesting increased parasympathetic tone for cardiac control. The mRNA levels of several components of the renin-angiotensin system in the dorsal medulla were markedly reduced including renin (-80%), neprilysin (-40%), and the AT1a receptor (-40%). However, there was a 2-fold to 3-fold increase in the mRNA levels of the phosphatases PTP-1b and dual-specificity phosphatase 1 in the medulla of Ang-(1-7) fusion protein-treated rats. Our finding that replacement of Ang-(1-7) in the brain of (mRen2)27 rats reverses in part the hypertension and baroreflex impairment is consistent with a functional deficit of Ang-(1-7) in this hypertensive strain. We conclude that the increased mRNA expression of phosphatases known to counteract the phosphoinositol 3 kinase and mitogen-activated protein kinases, and the reduction of renin and AT1a receptor mRNA levels may contribute to the reduction in arterial pressure and improvement in baroreflex sensitivity in response to Ang-(1-7).
Maria A Garcia-Espinosa; Hossam A Shaltout; Patricia E Gallagher; Mark C Chappell; Debra I Diz
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  60     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-15     Completed Date:  2012-12-26     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  150-7     Citation Subset:  IM    
Radiation Oncology Department †Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1032, USA.
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MeSH Terms
Angiotensin I / genetics,  metabolism*
Arterial Pressure* / genetics
Autonomic Nervous System / physiopathology
Baroreflex* / genetics
Brain / metabolism*,  physiopathology
Disease Models, Animal
Dual Specificity Phosphatase 1 / genetics,  metabolism
Gene Expression Regulation
Gene Transfer Techniques
Genetic Therapy*
Heart Rate
Hypertension / genetics,  metabolism,  physiopathology,  therapy*
Neprilysin / genetics,  metabolism
Peptide Fragments / genetics,  metabolism*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics,  metabolism
RNA, Messenger / metabolism
Rats, Transgenic
Receptor, Angiotensin, Type 1 / genetics,  metabolism
Renin / genetics,  metabolism*
Renin-Angiotensin System / genetics
Time Factors
Grant Support
Reg. No./Substance:
0/Agtr1a protein, rat; 0/Peptide Fragments; 0/RNA, Messenger; 0/Receptor, Angiotensin, Type 1; 0/Ren2 protein, mouse; 0/angiotensin I (1-7); 9041-90-1/Angiotensin I; EC Specificity Phosphatase 1; EC protein, rat; EC Tyrosine Phosphatase, Non-Receptor Type 1; EC protein, rat; EC; EC

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