Expression of human angiotensinogen-renin in rat - Effects on transcription and heart function

被引:3
作者
Bartel, S
Hoch, B
Vetter, D
Krause, EG
机构
[1] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany
[2] Humboldt Univ, Franz Volhard Clin, Berlin, Germany
关键词
hypertrophy; contraction; relaxation; angiotensin I; adrenergic receptor agonists;
D O I
10.1161/hy0202.103275
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
In double transgenic rats (dTGR) harboring the human angiotensinogen (hAOGEN) and human renin (hREN) genes, we studied cardiac transcript levels of hypertrophy-related, Ca2+ regulatory, and beta-adrenoceptor-associated proteins. The contractile properties and the cellular signaling of isolated hearts exposed to (-)isoproterenol and/or angiotensin (Ang) I were evaluated. dTGR developed hypertension of 174.1 +/- 7.6 versus 109.6 +/- 2.0 mm Hg (P<0.05) in Sprague-Dawley rats and heart hypertrophy. In hearts of dTGR, the transcript levels of ANP, beta-MHC, and alpha-MHC were altered (percentage versus Sprague-Dawley rats, 100%) by 304%, 178%, and 78%, respectively. Transcript levels of L-type Ca2+ channel, Ca2+ release channel, SERCA2a, phospholamban, G(i) and G(s)-proteins were unchanged. Isolated hearts of dTGR indicated higher baseline contractility versus Sprague-Dawley rats. (-)Isoproterenol-modified contractility occurred in both groups; however, the extent (predrug value, 100%) was less in hearts of dTGR versus Sprague-Dawley rats (+dP/dt, 310 +/- 42% versus 534 +/- 63%; P<0.05). Interestingly, (-) isoproterenol shortened the relaxation time by approximate to25% in both groups. This finding was reflected by a protein kinase A-related phospholamban phosphorylation. Ang I depressed the heart contractility but did not interact with the protein kinase A pathway. In conclusion, we have found that expression of the hAOGEN-hREN complex in dTGR elicited specific effects on transcripts of ANP and myofibrillar proteins. Although the beta-adrenergically mediated relaxation was not impaired in the hypertrophied hearts, the extent of beta-adrenergic inotropic responsiveness was reduced.
引用
收藏
页码:219 / 223
页数:5
相关论文
共 35 条
[1]   ANGIOTENSIN-II INCREASES SPONTANEOUS CONTRACTILE FREQUENCY AND STIMULATES CALCIUM CURRENT IN CULTURED NEONATAL RAT-HEART MYOCYTES - INSIGHTS INTO THE UNDERLYING BIOCHEMICAL-MECHANISMS [J].
ALLEN, IS ;
COHEN, NM ;
DHALLAN, RS ;
GAA, ST ;
LEDERER, WJ ;
ROGERS, TB .
CIRCULATION RESEARCH, 1988, 62 (03) :524-534
[2]   INCREASED MYOTHERMAL ECONOMY OF ISOMETRIC FORCE GENERATION IN COMPENSATED CARDIAC-HYPERTROPHY INDUCED BY PULMONARY-ARTERY CONSTRICTION IN THE RABBIT - A CHARACTERIZATION OF HEAT LIBERATION IN NORMAL AND HYPERTROPHIED RIGHT VENTRICULAR PAPILLARY-MUSCLES [J].
ALPERT, NR ;
MULIERI, LA .
CIRCULATION RESEARCH, 1982, 50 (04) :491-500
[3]   SARCOPLASMIC-RETICULUM GENE-EXPRESSION IN CARDIAC-HYPERTROPHY AND HEART-FAILURE [J].
ARAI, M ;
MATSUI, H ;
PERIASAMY, M .
CIRCULATION RESEARCH, 1994, 74 (04) :555-564
[4]   High human renin hypertension in transgenic rats [J].
Bohlender, J ;
Fukamizu, A ;
Lippoldt, A ;
Nomura, T ;
Dietz, R ;
Menard, J ;
Murakami, K ;
Luft, FC ;
Ganten, D .
HYPERTENSION, 1997, 29 (01) :428-434
[5]   Myocardial adrenergic dysfunction in rats with transgenic, human renin-dependent hypertension [J].
Bohlender, J ;
Hildenbrand, U ;
Wagner, KD ;
Günther, J ;
Hempel, P ;
Schlegel, WP ;
Luft, FC ;
Krause, EG ;
Bartel, S .
JOURNAL OF HYPERTENSION, 2001, 19 (08) :1453-1463
[6]   DESENSITIZATION OF ADENYLATE-CYCLASE AND INCREASE OF GI-ALPHA IN CARDIAC-HYPERTROPHY DUE TO ACQUIRED HYPERTENSION [J].
BOHM, M ;
GIERSCHIK, P ;
KNORR, A ;
LARISCH, K ;
WEISMANN, K ;
ERDMANN, E .
HYPERTENSION, 1992, 20 (01) :103-112
[7]   Altered inotropic responsiveness and gene expression of hypertrophied myocardium with captopril [J].
Brooks, WW ;
Bing, OHL ;
Boluyt, MO ;
Malhotra, A ;
Morgan, JP ;
Satoh, N ;
Colucci, WS ;
Conrad, CH .
HYPERTENSION, 2000, 35 (06) :1203-1209
[8]   INVESTIGATION OF THE MECHANISMS UNDERLYING THE INCREASED CONTRACTION OF HYPERTROPHIED VENTRICULAR MYOCYTES ISOLATED FROM THE SPONTANEOUSLY HYPERTENSIVE RAT [J].
BROOKSBY, P ;
LEVI, AJ ;
JONES, JV .
CARDIOVASCULAR RESEARCH, 1993, 27 (07) :1268-1277
[9]   The cardiac beta-adrenoceptor-mediated signaling pathway and its alterations in hypertensive heart disease [J].
Castellano, M ;
Bohm, M .
HYPERTENSION, 1997, 29 (03) :715-722
[10]   Intracellular angiotensin II regulates the inward calcium current in cardiac myocytes [J].
De Mello, WC .
HYPERTENSION, 1998, 32 (06) :976-982