|In vivo expression of angiotensin-(1-7) lowers blood pressure and improves baroreflex function in transgenic (mRen2)27 rats.|
|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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|Type: Journal Article|
|Title: Journal of cardiovascular pharmacology Volume: 60 ISSN: 1533-4023 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2012 Aug|
|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|
|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.|
|APA/MLA Format Download EndNote Download BibTex|
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
Hypertension / genetics, metabolism, physiopathology, therapy*
Neprilysin / genetics, metabolism
Peptide Fragments / genetics, metabolism*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics, metabolism
RNA, Messenger / metabolism
Receptor, Angiotensin, Type 1 / genetics, metabolism
Renin / genetics, metabolism*
Renin-Angiotensin System / genetics
|P01 HL051952/HL/NHLBI NIH HHS; R01 HL056973/HL/NHLBI NIH HHS|
|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 126.96.36.199/Dual Specificity Phosphatase 1; EC 188.8.131.52/Dusp1 protein, rat; EC 184.108.40.206/Protein Tyrosine Phosphatase, Non-Receptor Type 1; EC 220.127.116.11/Ptpn1 protein, rat; EC 18.104.22.168/Renin; EC 22.214.171.124/Neprilysin|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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