BACKGROUND: Since first reports demonstrated interactions between the natriuretic peptide (NPS) and renin-angiotensin system (RAS), our experiments should clarify whether cardiac brain natriuretic peptide (BNP) is regulated in mice genetically altered for components of the RAS. METHODS AND RESULTS: The study was carried out in hypotensive AT1- and angiotensinogen (ANG)-, and normotensive AT2-knockout mice, and in hypertensive animals overexpressing ANG and wildtype controls of each genotype. Ventricular BNP expression was analyzed by RNase-protection assay (RPA) (n=6). Cardiac fibrosis was visualized by Sirius red staining. While ANG overexpression increases cardiac BNP-mRNA expression (1035+/-210 vs. wildtype: 405+/-95 in PSL/mm(2), P<0.01), its deficiency had no influence. Both AT1- and AT2-knockouts showed significantly decreased BNP-mRNA concentrations (AT1: 21+/-6 vs. wildtype: 139+/-28 in PSL/mm(2), P<0.001; AT2: 8+/-2 vs. 19+/-3 in PSL/mm(2), P<0.05). These alterations correlate to reduced cardiac fibrosis in AT2-deficient animals, and an unchanged matrix content in ANG knockouts. CONCLUSIONS: Increased BNP-mRNA levels in hypertensive ANG-overexpressing mice and decreased BNP in hypotensive AT1-deficient animals suggest that this mRNA expression is blood pressure-dependent. However, the observed alterations of fibrosis and the unchanged BNP in hypotensive ANG knockouts and impaired BNP-mRNA expression in normotensive AT2-deficient mice demonstrate a direct interaction of the RAS and NPS that is fibrosis- rather than blood pressure-dependent.
BACKGROUND: Since first reports demonstrated interactions between the natriuretic peptide (NPS) and renin-angiotensin system (RAS), our experiments should clarify whether cardiac brain natriuretic peptide (BNP) is regulated in mice genetically altered for components of the RAS. METHODS AND RESULTS: The study was carried out in hypotensiveAT1- and angiotensinogen (ANG)-, and normotensive AT2-knockout mice, and in hypertensive animals overexpressing ANG and wildtype controls of each genotype. Ventricular BNP expression was analyzed by RNase-protection assay (RPA) (n=6). Cardiac fibrosis was visualized by Sirius red staining. While ANG overexpression increases cardiac BNP-mRNA expression (1035+/-210 vs. wildtype: 405+/-95 in PSL/mm(2), P<0.01), its deficiency had no influence. Both AT1- and AT2-knockouts showed significantly decreased BNP-mRNA concentrations (AT1: 21+/-6 vs. wildtype: 139+/-28 in PSL/mm(2), P<0.001; AT2: 8+/-2 vs. 19+/-3 in PSL/mm(2), P<0.05). These alterations correlate to reduced cardiac fibrosis in AT2-deficient animals, and an unchanged matrix content in ANG knockouts. CONCLUSIONS: Increased BNP-mRNA levels in hypertensiveANG-overexpressing mice and decreased BNP in hypotensive AT1-deficient animals suggest that this mRNA expression is blood pressure-dependent. However, the observed alterations of fibrosis and the unchanged BNP in hypotensiveANG knockouts and impaired BNP-mRNA expression in normotensive AT2-deficient mice demonstrate a direct interaction of the RAS and NPS that is fibrosis- rather than blood pressure-dependent.
Authors: S Heringer-Walther; M C V Moreira; N Wessel; J L Saliba; J Silvia-Barra; J L B Pena; S Becker; W E Siems; H P Schultheiss; T Walther Journal: Heart Date: 2005-03 Impact factor: 5.994
Authors: Chia-Ying Liu; Susan R Heckbert; Shenghan Lai; Bharath Ambale-Venkatesh; Mohammad R Ostovaneh; Robyn L McClelland; João A C Lima; David A Bluemke Journal: J Am Coll Cardiol Date: 2017-12-26 Impact factor: 24.094
Authors: Joep H M van Esch; Florian Gembardt; Anja Sterner-Kock; Silvia Heringer-Walther; Thu H Le; Dirk Lassner; Theo Stijnen; Thomas M Coffman; Heinz-Peter Schultheiss; A H Jan Danser; Thomas Walther Journal: Cardiovasc Res Date: 2010-01-12 Impact factor: 10.787