Enhanced cardiac angiotensinogen gene expression and angiotensin converting enzyme activity in tachypacing-induced heart failure in rats

Finckh, Maria R.; Hellmann, W.; Ganten, Detlev; Furtwängler, A.; Allgeier, Juergen; Boltz, M. A.; Holtz, J.

doi:10.1007/bf02191528

Cited by 37 publications

(14 citation statements)

References 44 publications

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Section: Introductionmentioning

confidence: 99%

“…Activation of the cardiac RAS has been demonstrated to occur after myocardial infarction (13,14). This activation involves an increased transcription of the gene encoding the ACE mRNA (14)(15)(16). The assessment of cardiac RAS, however, has been usually performed in chronically infarcted individuals with variable degrees of heart failure (13,17).…”

Section: Introductionmentioning

confidence: 99%

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Increased angiotensin-converting enzyme activity in the left ventricle after infarction

Busatto

Cicilini²,

Mill³

1997

Braz J Med Biol Res

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An increase in angiotensin-converting enzyme (ACE) activity has been observed in the heart after myocardial infarction (MI). Since most studies have been conducted in chronically infarcted individuals exhibiting variable degrees of heart failure, the present study was designed to determine ACE activity in an earlier phase of MI, before heart failure development. MI was produced in 3-month old male Wistar rats by ligation of the anterior branches of the left coronary artery, control rats underwent sham surgery and the animals were studied 7 or 15 days later. Hemodynamic data obtained for the anesthetized animals showed normal values of arterial blood pressure and of end-diastolic pressure in the right and left ventricular cavities of MI rats. Right and left ventricular (RV, LV) muscle and scar tissue homogenates were prepared to determine ACE activity in vitro by measuring the velocity of His-Leu release from the synthetic substrate Hyp-His-Leu. ACE activity was corrected to the tissue wet weight and is reported as nmol His-Leu g -1 min -1 . No significant change in ACE activity in the RV homogenates was demonstrable. A small nonsignificant increase of ACE activity (11 ± 9%; P>0.05) was observed 7 days after MI in the surviving left ventricular muscle. Two weeks after surgery, however, ACE activity was 46 ± 11% (P<0.05) higher in infarcted rats compared to sham-operated rats. The highest ACE activity was demonstrable in the scar tissue homogenate. In rats studied two weeks after surgery, ACE activity in the LV muscle increased from 105 ± 7 nmol His-Leu g -1 min -1 in control hearts to 153 ± 11 nmol His-Leu g -1 min -1 (P<0.05) in the remaining LV muscle of MI rats and to 1051 ± 208 nmol His-Leu g -1 min -1 (P<0.001) in the fibrous scar. These data indicate that ACE activity increased in the heart after infarction before heart failure was demonstrable by hemodynamic measurements. Since the blood vessels of the scar drain to the remaining LV myocardium, the high ACE activity present in the fibrous scar may increase the angiotensin II concentration and decrease bradykinin in the cardiac tissues surrounding the infarcted area. The increased angiotensin II in the fibrous scar may contribute to the reactive fibrosis and hypertrophy in the left ventricular muscle surviving infarction.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased angiotensin-converting enzyme activity in the left ventricle after infarction

Busatto

Cicilini²,

Mill³

1997

Braz J Med Biol Res

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“…Recent studies have shown that the cardiac expression of angiotensinogen and ACE is increased in experimental heart failure ( 12,13,17,18). Cardiac ACE activity as well as the rate of angiotensin-II production is enhanced in hypertrophied rat hearts (12) and associated with altered diastolic properties possibly contributing to the vulnerability of diastolic function in hypertrophy during hypoperfusion ( 19).…”

Section: Introductionmentioning

confidence: 99%

Increased angiotensin-I converting enzyme gene expression in the failing human heart. Quantification by competitive RNA polymerase chain reaction.

Studer¹,

Reinecke²,

Müller³

et al. 1994

J. Clin. Invest.

187

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Local activation of the components of the renin angiotensin system in the heart is regarded as an important modulator of cardiac phenotype and function; however, little is known about their presence, regulation, and potential activation in the human heart. To investigate the gene expression of major angiotensin-II-forming enzymes in left ventricles of normal (n = 9) and failing human hearts (n = 20), we established a competitive RNA-polymerase chain reaction (PCR) for mRNA quantification of angiotensin-I converting enzyme (ACE) and human heart chymase. For each gene, competitor RNA targets with small internal deletions were used as internal standards to quantify the original number of transcripts and to control reverse transcription and PCR. In PCR, each target and the corresponding competitor were amplified by competing for the same primer oligonucleotides. The variability of ACE RNA-PCR was 11% indicating a high reproducibility of this method. In addition, ACE mRNA levels obtained by competitive RNA-PCR correlated favorably with traditional slot blot hybridization (r = 0.69, n = 10; P < 0.05). Compared with nonfailing hearts, the number of ACE transcripts referred to 100 ng of total RNA was increased threefold in patients with chronic heart failure (4.2±2.5 vs. 12.8±6 x 105; P < 0.0005). In contrast, no significant difference was found in chymase gene expression between normal and failing hearts. Thus, the expression of the cardiac ACE but not of human heart chymase is upregulated in failing human heart indicating an activation of the cardiac renin-angiotensin system in patients with advanced heart failure. (J. Clin. Invest. 1994. 94:301-310.)

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“…Some authors have reported a transient increase of AOGEN mRNA in myocardial infarction and failure (175). A doubling of AOGEN gene expression as compared to control rats has been described in ventricular myocardium during cardiac chronic tachipacing (176). In chronic heart failure induced by ligation of the left coronary artery in rats an enhancement of ACE mRNA was found, which correlated with the cardiac ACE activity, but not with its activity in other organs (177).…”

Section: Heartmentioning

confidence: 96%

The Role of the Renin-Angiotensin System in Cardiovascular Disease.

et al. 1994

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Recent findings have increased our understanding of the role of the renin-angiotensin system in cardiovascular diseases. This was possible by the progress made in molecular biology and the import of this methodology into cardiovascular research by several groups in the past few years. Studies by these groups accumulated evidence especially for the existence and physiological importance of organ-based renin-angiotensin systems and their involvement in the pathogenesis of hypertension and the accompanying disorders of the heart, the kidney, and the vessels. This Review will focus mainly on the relevance of the local renin-angiotensin systems for cardiovascular diseases and the value of transgenic animals as models to analyse these systems (Hypertens Res 1994; 17: 1-16).

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Enhanced cardiac angiotensinogen gene expression and angiotensin converting enzyme activity in tachypacing-induced heart failure in rats

Cited by 37 publications

References 44 publications

Increased angiotensin-converting enzyme activity in the left ventricle after infarction

Increased angiotensin-converting enzyme activity in the left ventricle after infarction

Increased angiotensin-I converting enzyme gene expression in the failing human heart. Quantification by competitive RNA polymerase chain reaction.

The Role of the Renin-Angiotensin System in Cardiovascular Disease.

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