(Hypertension. 2000;36:1065.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Mechanisms of Increased Susceptibility to Angiotensin II–Induced Apoptosis in Ventricular Cardiomyocytes of Spontaneously Hypertensive Rats
From the Vascular Pathophysiology Unit, School of Medicine, University of Navarra, Pamplona, Spain.
Correspondence to Dr Javier Díez, Unidad de Fisiopatología Vascular, Facultad de Medicina, C/Irunlarrea s/n, 31080 Pamplona, Spain. E-mail jadimar{at}unav.es
Abstract—Previous findings have
shown that hypotensive doses of losartan prevent the excess of
apoptosis present in the hypertrophied left ventricle of
adult spontaneously hypertensive rats (SHR). This study was designed to
determine whether angiotensin II facilitates
apoptosis in cardiomyocytes of adult SHR. Primary
cultures of ventricular cardiomyocytes from
30-week-old normotensive Wistar-Kyoto rats (WKY) and SHR with left
ventricular hypertrophy were exposed to
10-9 mol/L angiotensin II for 24
hours. Apoptotic cells were assessed by terminal
deoxynucleotidyl transferase assay and confirmed by
Annexin V detection. The expression of Bax-
, Bcl-2,
p53, and caspase-3 proteins was assessed by Western blot
assays. The expression of BAX gene was assessed by
Northern blot. Angiotensin II increased
(P<0.01) cardiomyocyte apoptosis,
and this effect was higher (P<0.001) in SHR cells than
in WKY cells. Whereas losartan (10-7
mol/L) blocked the apoptotic effect of the octapeptide in cells
from the two strains of rats, PD123319 (10-7
mol/L) inhibited angiotensin II–mediated apoptosis
only in SHR cells. Angiotensin II stimulated
(P<0.01) Bax- protein, and this effect was higher
(P<0.01) in SHR cells than in WKY cells.
Angiotensin II did not modify Bcl-2, p53, and BAX mRNA in
cells from the two strains of rats. Angiotensin II induced
a similar increase (P<0.05) in the ratio
caspase-3/procaspase-3 (an index of caspase-3 activation) in
cardiomyocytes from the two strains of rats. The
present in vitro results indicate that SHR
cardiomyocytes exhibit enhanced susceptibility to
angiotensin II–induced apoptosis. Ligand binding
to angiotensin II type 1 and type 2 receptors leading to
changes in posttranscriptional processing of Bax- and accumulation
of this proapoptotic protein may be involved in the abnormal
response of SHR cardiomyocytes. These data support a role
for angiotensin II in apoptosis observed in the
left ventricle of these rats.
Key Words: angiotensin II • apoptosis • myocytes • rats, spontaneously hypertensive
This article has been cited by other articles:
 |
|
 |
|
  N. Lopez, N. Varo, J. Diez, and M. A. Fortuno Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists? Cardiovasc Res, August 1, 2007; 75(3): 536 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Quadrilatero and J. W. E. Rush Increased DNA fragmentation and altered apoptotic protein levels in skeletal muscle of spontaneously hypertensive rats J Appl Physiol, October 1, 2006; 101(4): 1149 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Bahi, J. Zhang, M. Llovera, M. Ballester, J. X. Comella, and D. Sanchis Switch from Caspase-dependent to Caspase-independent Death during Heart Development: ESSENTIAL ROLE OF ENDONUCLEASE G IN ISCHEMIA-INDUCED DNA PROCESSING OF DIFFERENTIATED CARDIOMYOCYTES J. Biol. Chem., August 11, 2006; 281(32): 22943 - 22952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Shimojo, S. Jesmin, S. Zaedi, M. Soma, S. Maeda, I. Yamaguchi, K. Goto, and T. Miyauchi Changes in important apoptosis-related molecules in the endothelin-1-induced hypertrophied cardiomyocytes: effect of the pretreatment with eicosapentaenoic Acid. Experimental Biology and Medicine, June 1, 2006; 231(6): 932 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Grishko, V. Pastukh, V. Solodushko, M. Gillespie, J. Azuma, and S. Schaffer Apoptotic cascade initiated by angiotensin II in neonatal cardiomyocytes: role of DNA damage Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2364 - H2372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gonzalez, M. A Fortuno, R. Querejeta, S. Ravassa, B. Lopez, N. Lopez, and J. Diez Cardiomyocyte apoptosis in hypertensive cardiomyopathy Cardiovasc Res, September 1, 2003; 59(3): 549 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. U Braun, P. Szalai, R. H Strasser, and M. M Borst Right ventricular hypertrophy and apoptosis after pulmonary artery banding: regulation of PKC isozymes Cardiovasc Res, September 1, 2003; 59(3): 658 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Fortuno, A. Gonzalez, S. Ravassa, B. Lopez, and J. Diez Clinical implications of apoptosis in hypertensive heart disease Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1495 - H1506. [Full Text] [PDF]
|
|
|
|
|
|
S. Der Sarkissian, E.-L. Marchand, D. Duguay, P. Hamet, and D. deBlois Reversal of interstitial fibroblast hyperplasia via apoptosis in hypertensive rat heart with valsartan or enalapril Cardiovasc Res, March 1, 2003; 57(3): 775 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Li, J. Suzuki, E. Bayna, F.-M. Zhang, E. Dalle Molle, A. Clark, R. L. Engler, and W. Y. W. Lew Lipopolysaccharide induces apoptosis in adult rat ventricular myocytes via cardiac AT1 receptors Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H461 - H467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Yaniv, M. Shilkrut, R. Lotan, G. Berke, S. Larisch, and O. Binah Hypoxia predisposes neonatal rat ventricular myocytes to apoptosis induced by activation of the Fas (CD95/Apo-1) receptor: Fas activation and apoptosis in hypoxic myocytes Cardiovasc Res, June 1, 2002; 54(3): 611 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gonzalez, B. Lopez, S. Ravassa, R. Querejeta, M. Larman, J. Diez, and M. A. Fortuno Stimulation of Cardiac Apoptosis in Essential Hypertension: Potential Role of Angiotensin II Hypertension, January 1, 2002; 39(1): 75 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ono, Y. Ono, A. Takanohashi, H. Matsuoka, and E. D. Frohlich Apoptosis and Glomerular Injury After Prolonged Nitric Oxide Synthase Inhibition in Spontaneously Hypertensive Rats Hypertension, December 1, 2001; 38(6): 1300 - 1306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Fortuno, S. Ravassa, A. Fortuno, G. Zalba, and J. Diez Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension: Mechanisms and Potential Management Hypertension, December 1, 2001; 38(6): 1406 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Mascareno, M. El-Shafei, N. Maulik, M. Sato, Y. Guo, D. K. Das, and M.A.Q. Siddiqui JAK/STAT Signaling Is Associated With Cardiac Dysfunction During Ischemia and Reperfusion Circulation, July 17, 2001; 104(3): 325 - 329. [Abstract] [Full Text] [PDF]
|
|