Apoptosis is not increased in myocardium overexpressing type 2 angiotensin II receptor in transgenic mice

被引:47
作者
Sugino, H
Ozono, R
Kurisu, S
Matsuura, H
Ishida, M
Oshima, T
Kambe, M
Teranishi, Y
Masaki, H
Matsubara, H
机构
[1] Hiroshima Univ, Fac Med, Dept Internal Med 1, Minami Ku, Hiroshima 7348551, Japan
[2] Hiroshima Univ, Fac Med, Dept Clin Lab Med, Minami Ku, Hiroshima 7348551, Japan
[3] Hiroshima Univ, Fac Med, Dept Physiol 2, Minami Ku, Hiroshima 7348551, Japan
[4] Kansai Med Univ, Dept Internal Med, Osaka, Japan
关键词
myocytes; cardiac; apoptosis; mice; transgenic; angiotensin II; L158809;
D O I
10.1161/01.HYP.37.6.1394
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
To determine whether angiotensin type 2 (AT(2)) receptor stimulation induces apoptosis in cardiomyocytes in vivo, we developed transgenic mice overexpressing the AT(2) receptor in a cardiac-specific manner, using the alpha -myosin heavy-chain promoter. Ten- to 12-week-old male homozygous transgenic mice (n=44) and wild-type mice (n=44) were used. Both transgenic and wild-type mice were given either saline (control), a subpressor dose of angiotensin II (100 ng . kg(-1) . min(-1)), a presser dose of angiotensin Il (1000 ng . kg(-1) . min(-1)) for 14 days, a presser dose of angiotensin II for 28 days to investigate the effects of stimulation on both angiotensin type 1 (AT(1)) and AT(2) receptors, the AT(1) antagonist L158809 alone, or a combination of angiotensin IT (1000 ng . kg(-1) . min(-1)) and L158809 for 14 days to investigate the effects of selective AT(2) receptor stimulation. Apoptosis was analyzed in paraffin-embedded ventricular sections by the terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) technique. In both transgenic and wild-type mice, administration of a subpressor dose of angiotensin TT, L158809, or a combination of: angiotensin II and L158809 did not significantly affect the tail-cuff blood pressure or heart-to-body weight ratio, whereas administration of a presser dose of angiotensin Il for 14 or 28 days significantly increased blood pressure and the heart-to-body weight ratio. However, there was no statistical difference between the effects of angiotensin II in transgenic and wild-type mice. The number of TUNEL-positive nuclei was approximate to0 to 10 per 100 000 cardiomyocytes, with no difference between transgenic and wild-type mice, regardless of saline infusion or any stimulation. In infarcted canine myocardial tissue sections for positive control, the number of TUNEL-positive nuclei was increased by 13.8 to 19.1 times compared with those in the noninfarcted myocardium. In conclusion, angiotensin IT infusion for a period of 28 days failed to induce cardiomyocyte apoptosis regardless of the presence or absence of cardiac AT(2) receptor overexpression. It is unlikely that in mice the AT(2) receptor is a strong signal to induce cardiomyocyte apoptosis in vivo.
引用
收藏
页码:1394 / 1398
页数:5
相关论文
共 28 条
  • [11] Overexpression of Bax protein and enhanced apoptosis in the left ventricle of spontaneously hypertensive rats -: Effects of AT1 blockade with losartan
    Fortuño, MA
    Ravassa, S
    Etayo, JC
    Díez, J
    [J]. HYPERTENSION, 1998, 32 (02) : 280 - 286
  • [12] Effects of ACE inhibition on cardiomyocyte apoptosis in dogs with heart failure
    Goussev, A
    Sharov, VG
    Shimoyama, H
    Tanimura, M
    Lesch, M
    Goldstein, S
    Sabbah, HN
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1998, 275 (02): : H626 - H631
  • [13] Apoptosis - Basic mechanisms and implications for cardiovascular disease
    Haunstetter, A
    Izumo, S
    [J]. CIRCULATION RESEARCH, 1998, 82 (11) : 1111 - 1129
  • [14] INAGAMI T, 1994, HYPERTENS RES, V17, P87
  • [15] Angiotensin II induces apoptosis of adult ventricular myocytes in vitro
    Kajstura, J
    Cigola, E
    Malhotra, A
    Li, P
    Cheng, W
    Meggs, LG
    Anversa, P
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1997, 29 (03) : 859 - 870
  • [16] Biological roles of angiotensin II via its type 2 receptor during rat follicle atresia
    Kotani, E
    Sugimoto, M
    Kamata, H
    Fujii, N
    Saitoh, M
    Usuki, S
    Kubo, T
    Song, KF
    Miyazaki, M
    Murakami, K
    Miyazaki, H
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1999, 276 (01): : E25 - E33
  • [17] Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell
    Leri, A
    Claudio, PP
    Li, Q
    Wang, XW
    Reiss, K
    Wang, SG
    Malhotra, A
    Kajstura, J
    Anversa, P
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (07) : 1326 - 1342
  • [18] Genetic deletion of AT2 receptor antagonizes angiotensin II-induced apoptosis in fibroblasts of the mouse embryo
    Li, WG
    Ye, YH
    Fu, B
    Wang, JZ
    Yu, LF
    Ichiki, T
    Inagami, T
    Ichikawa, I
    Chen, XM
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 250 (01) : 72 - 76
  • [19] Increased cardiomyocyte apoptosis during the transition to heart failure in the spontaneously hypertensive rat
    Li, ZH
    Bing, OHL
    Long, XL
    Robinson, KG
    Lakatta, EG
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1997, 272 (05): : H2313 - H2319
  • [20] ANGIOTENSIN-II INCREASES PROTOONCOGENE EXPRESSION AND PHOSPHOINOSITIDE TURNOVER IN VASCULAR SMOOTH-MUSCLE CELLS VIA THE ANGIOTENSIN-II AT1 RECEPTOR
    LYALL, F
    DORNAN, ES
    MCQUEEN, J
    BOSWELL, F
    KELLY, M
    [J]. JOURNAL OF HYPERTENSION, 1992, 10 (12) : 1463 - 1469