HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 31/2/193    most recent 00079.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Vellaichamy, E. Articles by Pandey, K. N. Search for Related Content PubMed PubMed Citation Articles by Vellaichamy, E. Articles by Pandey, K. N.

Genetic disruption of guanylyl cyclase/natriuretic peptide receptor-A upregulates ACE and AT1 receptor gene expression and signaling: role in cardiac hypertrophy

Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana

Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) signaling antagonizes the physiological effects mediated by the renin-angiotensin system (RAS). The objective of this study was to determine whether the targeted-disruption of Npr1 gene (coding for GC-A/NPRA) leads to the activation of cardiac RAS genes involved on the hypertrophic remodeling process. The Npr1 gene-knockout (Npr1^–/–) mice showed 30–35 mmHg higher systolic blood pressure (SBP) and a 63% greater heart weight-to-body weight (HW/BW) ratio compared with wild-type (Npr1^+/+) mice. The mRNA levels of both angiotensin-converting enzyme and angiotensin II type 1a receptor were increased by three- and fourfold, respectively, in Npr1^–/– null mutant mice hearts compared with the wild-type Npr1^+/+ mice hearts. In parallel, the expression levels of interleukin-6 and tumor necrosis factor- were increased by four- to fivefold, in Npr1^–/– mice hearts compared with control animals. The NF-B binding activity in nuclear extracts of Npr1^–/– mice hearts was increased by fourfold compared with wild-type Npr1^+/+ mice hearts. Treatments with captopril or hydralazine equally attenuated SBP; however, only captopril significantly decreased the HW/BW ratio and suppressed cytokine gene expression in Npr1^–/– mice hearts. The ventricular cGMP level was reduced by almost sixfold in Npr1^–/– mice compared with wild-type control mice. The results of the present study indicate that disruption of NPRA/cGMP signaling leads to the augmented expression of cardiac RAS pathways that promote the development of cardiac hypertrophy and remodeling.

angiotensin-converting enzyme; angiotensin II type 1 receptor; hypertension; cardiac hypertrophy; angiotensin II; cytokines

This article has been cited by other articles:

				P. Kumar and K. N. Pandey Cooperative Activation of Npr1 Gene Transcription and Expression by Interaction of Ets-1 and p300 Hypertension, July 1, 2009; 54(1): 172 - 178. [Abstract] [Full Text] [PDF]

				P. Li, D. Wang, J. Lucas, S. Oparil, D. Xing, X. Cao, L. Novak, M. B. Renfrow, and Y.-F. Chen Atrial Natriuretic Peptide Inhibits Transforming Growth Factor {beta}-Induced Smad Signaling and Myofibroblast Transformation in Mouse Cardiac Fibroblasts Circ. Res., February 1, 2008; 102(2): 185 - 192. [Abstract] [Full Text] [PDF]