| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2001;37:974.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Effects of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Type 1 Receptor Antagonist in Deoxycorticosterone Acetate–Salt Hypertensive Mice Lacking Ren-2 Gene
From the Hypertension and Vascular Research Division and Department of Biostatistics and Research Epidemiology (J.A.M.), Henry Ford Hospital, Detroit, Mich.
Correspondence to Nour-Eddine Rhaleb, PhD, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202. E-mail nrhaleb1{at}hfhs.org
We previously reported that inhibition of angiotensin-converting enzyme (ACE) prevented the hypertension and left ventricular hypertrophy induced by deoxycorticosterone acetate–salt (DOCA-salt) in 129/SvEvTac mice, which have 2 renin genes (Ren-1 and Ren-2). In the present study, we induced hypertension by uninephrectomy and DOCA-salt in mice having only the Ren-1 gene (C57BL/6J) and investigated the effect of an ACE inhibitor (ramipril, 4 mg · kg-1 · d-1) and an angiotensin type 1 (AT1) receptor antagonist (L-158809, 4 mg · kg-1 · d-1) on the development of hypertension, cardiac hypertrophy, and renal injury. After 4 weeks of treatment, systolic blood pressure in DOCA-salt mice was significantly increased (128±2 mm Hg) compared with controls (109±2 mm Hg) (P<0.001), while plasma renin concentration was decreased by 97% (P<0.001). DOCA-salt also induced left ventricular and renal hypertrophy and renal damage as manifested by proteinuria. Collagen content in the left ventricle and kidney was significantly higher in DOCA-salt mice (P<0.001). Urinary albumin (P<0.05) and proliferating cell nucleic antigen–positive cells in the tubules and interstitium of the renal cortex (P<0.001) were significantly increased in the DOCA-salt group. Neither the ACE inhibitor nor the AT1 antagonist had any antihypertensive effect; however, they partially prevented cardiac hypertrophy and completely inhibited left ventricular collagen deposition. In the kidney, both the ACE inhibitor and AT1 antagonist partially reduced the increase in collagen but had no effect on hypertrophy. They also significantly prevented the effect of DOCA-salt on urinary albumin and proliferating cell nucleic antigen expression in the kidney. Despite the lack of an antihypertensive effect, both ACE inhibitor and AT1 antagonist prevented cardiac remodeling and renal damage. Our results indicate that ACE inhibitors and AT1 antagonists exert beneficial effects on the heart and kidney in DOCA-salt hypertensive mice independently of their effects on blood pressure.
Key Words: mice • deoxycorticosterone • hypertension • angiotensin-converting enzyme inhibitors • receptors, angiotensin • renal injury • cardiac remodeling
This article has been cited by other articles:
 |
|
 |
|
  W. Huang, J. Rubinstein, A. R. Prieto, L. V. Thang, and D. H. Wang Transient Receptor Potential Vanilloid Gene Deletion Exacerbates Inflammation and Atypical Cardiac Remodeling After Myocardial Infarction Hypertension, February 1, 2009; 53(2): 243 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, D. Babankova, J. Huang, G. M. Swain, and D. H. Wang Deletion of Transient Receptor Potential Vanilloid Type 1 Receptors Exaggerates Renal Damage in Deoxycorticosterone Acetate-Salt Hypertension Hypertension, August 1, 2008; 52(2): 264 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Barrick, M. Rojas, R. Schoonhoven, S. S. Smyth, and D. W. Threadgill Cardiac response to pressure overload in 129S1/SvImJ and C57BL/6J mice: temporal- and background-dependent development of concentric left ventricular hypertrophy Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2119 - H2130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Peng, O. A. Carretero, T.-D. Liao, E. L. Peterson, and N.-E. Rhaleb Role of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline in the Antifibrotic and Anti-Inflammatory Effects of the Angiotensin-Converting Enzyme Inhibitor Captopril in Hypertension Hypertension, March 1, 2007; 49(3): 695 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Bowers, K. A. Katki, A. Rao, M. Koehler, P. Patel, A. Spiekerman, D. J. DiPette, and S. C. Supowit Role of Calcitonin Gene-Related Peptide in Hypertension-Induced Renal Damage Hypertension, July 1, 2005; 46(1): 51 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Supowit, A. Rao, M. C. Bowers, H. Zhao, G. Fink, B. Steficek, P. Patel, K. A. Katki, and D. J. DiPette Calcitonin Gene-Related Peptide Protects Against Hypertension-Induced Heart and Kidney Damage Hypertension, January 1, 2005; 45(1): 109 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Perez-Rivera, G. D. Fink, and J. J. Galligan Increased Reactivity of Murine Mesenteric Veins to Adrenergic Agonists: Functional Evidence Supporting Increased {alpha}1-Adrenoceptor Reserve in Veins Compared with Arteries J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 350 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hartner, N. Cordasic, B. Klanke, R. Veelken, and K. F. Hilgers Strain differences in the development of hypertension and glomerular lesions induced by deoxycorticosterone acetate salt in mice Nephrol. Dial. Transplant., October 1, 2003; 18(10): 1999 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Wang, E. Hummler, J. Nussberger, S. Clement, G. Gabbiani, H. R. Brunner, and M. Burnier Blood Pressure, Cardiac, and Renal Responses to Salt and Deoxycorticosterone Acetate in Mice: Role of Renin Genes J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1509 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Beggah, B. Escoubet, S. Puttini, S. Cailmail, V. Delage, A. Ouvrard-Pascaud, B. Bocchi, M. Peuchmaur, C. Delcayre, N. Farman, et al. From the Cover: Reversible cardiac fibrosis and heart failure induced by conditional expression of an antisense mRNA of the mineralocorticoid receptor in cardiomyocytes PNAS, May 14, 2002; 99(10): 7160 - 7165. [Abstract] [Full Text] [PDF]
|
|