Angiotensin converting enzyme inhibition in patients with congestive heart failure.

Gavras, Haralambos; Faxon, David P.; Berkoben, John P.; Brunner, H R; Ryan, Thomas J.

doi:10.1161/01.cir.58.5.770

Cited by 211 publications

(49 citation statements)

References 33 publications

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“…Angiotensin-converting enzyme inhibitors (ACEi) 1 improve cardiac function and remodeling and prolong survival in patients with heart failure (HF) (1)(2)(3)(4)(5)(6)(7). The cardioprotective effect of ACEi may be due to blockade of the renin-angiotensin system and/or inhibition of kinin destruction (6,8,9).…”

Section: Introductionmentioning

confidence: 99%

“…However, the effect of the AT 1 -ant may not be entirely due to blockade of the AT 1 receptor. Angiotensin receptors comprise two major subtypes, AT 1 and AT 2 (19). When the AT 1 receptor is blocked, plasma renin and angiotensins increase (20); angiotensin may act on AT 2 receptors, which could have an antitrophic effect (21,22) either directly or via the release of autacoids such as kinins and nitric oxide (NO) (23,24) and consequently may contribute to the therapeutic effect of AT 1 -ant by a mechanism similar to kinins.…”

Section: Introductionmentioning

confidence: 99%

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Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors.

Liu¹,

Yang²,

Sharov³

et al. 1997

J. Clin. Invest.

567

407

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Angiotensin-converting enzyme inhibitors (ACEi) improve cardiac function and remodeling and prolong survival in patients with heart failure (HF). Blockade of the renin-angiotensin system (RAS) with an angiotensin II type 1 receptor antagonist (AT 1 -ant) may have a similar beneficial effect. In addition to inhibition of the RAS, ACEi may also act by inhibiting kinin destruction, whereas AT 1 -ant may block the RAS at the level of the AT 1 receptor and activate the angiotensin II type 2 (AT 2 ) receptor. Using a model of HF induced by myocardial infarction (MI) in rats, we studied the role of kinins in the cardioprotective effect of ACEi. We also investigated whether an AT 1 -ant has a similar effect and whether these effects are partly due to activation of the AT 2 receptor. Two months after MI, rats were treated for 2 mo with: (

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors.

Liu¹,

Yang²,

Sharov³

et al. 1997

J. Clin. Invest.

567

407

View full text Add to dashboard Cite

show abstract

“…Although initially known for its vasoconstrictive action, the adverse effects of ANG II elevation on the heart independent of its hemodynamic influence were recognized in the early 1970s (7,16), and the cardioprotective outcomes of the pharmacological interventions that either prevent the ANG II formation from the inactive angiotensinogen precursor (14) or inhibit its interaction with specific receptors (15,48) are now well appreciated in clinical practice (6,13,17).…”

mentioning

confidence: 99%

Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression

Schwartz¹,

Duka²,

Duka³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Schwartz, Faina, Arvi Duka, Irena Duka, Jing Cui, and Haralambos Gavras. Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression. Am J Physiol Heart Circ Physiol 287: H1957-H1966, 2004. First published July 8, 2004 doi:10.1152/ajpheart.00568.2004.-Although the central role of ANG II in cardiovascular homeostasis is well appreciated, the molecular circuitry of its many actions is not completely understood. With the use of serial analysis of gene expression to assess global transcriptional changes in the heart of mice after continuous 7-day ANG II administration, we identified patterns of gene expression indicative of cardiac remodeling, including coordinate regulation of genes previously described in a context of processes associated with hypertrophy and fibrosis. In addition, we discovered several novel ANG II targets, including characterized genes of known function, recently annotated genes of unknown function, and the putative genes not yet present in current databases. The serial analysis of gene expression approach to assess the role of ANG II presented in this report provides new venues for inquiries into ANG II-mediated cardiac function.genome-wide transcriptional profiling; hypertension; cardiac remodeling; hypertrophy; fibrosis THE KEY ROLE of ANG II in cardiovascular homeostasis is well documented. Although initially known for its vasoconstrictive action, the adverse effects of ANG II elevation on the heart independent of its hemodynamic influence were recognized in the early 1970s (7, 16), and the cardioprotective outcomes of the pharmacological interventions that either prevent the ANG II formation from the inactive angiotensinogen precursor (14) or inhibit its interaction with specific receptors (15, 48) are now well appreciated in clinical practice (6,13,17).Experimental animal studies have shown that ANG II administration can cause multifocal myocardial lesions (16, 47), and, via ANG II type 1 receptors, directly induce cardiac remodeling that involves myocyte hypertrophy (9, 25), fibroblast proliferation, and subsequent fibrosis (47), thus leading to the development of pathological cardiac hypertrophy and, ultimately, heart failure. Both in vivo and in vitro studies revealed that the ANG II effects in the heart are accompanied by changes in gene expression in the cardiac myocytes, fibroblasts, and endothelial cells (24). While the queries of selected ANG II targets supplied important information on several molecular pathways underlying the physiological and pathophysiological actions of ANG II, an all-inclusive view is provided by the genome-wide transcriptional profiling that offers an opportunity to connect separate pieces of the puzzle through the identification of the new players not intuitively obvious from our present understanding of physiology. Thus simultaneous evaluation of 4,000 genes by the use of microarray technology to query the quantitative changes in left ventricular RNA in response to ANG II-induced progression, and, subsequently, regre...

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“…illions of patients are treated with angiotensin I-converting enzyme (ACE) or kininase II inhibitors against hypertension, 1 congestive heart failure, diabetic nephropathy and other conditions. 2,3 The dual effects of these inhibitors in blocking angiotensin (Ang) II release and the catabolism of bradykinin 4 (BK) cannot account for all their actions.…”

mentioning

confidence: 99%

Angiotensin 1-9 and 1-7 Release in Human Heart

et al. 2002

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Abstract-Human heart tissue enzymes cleave angiotensin (Ang) I to release Ang 1-9, Ang II, or Ang 1-7. In atrial homogenate preparations, cathepsin A (deamidase) is responsible for 65% of the liberated Ang 1-9. Ang 1-7 was released (88% to 100%) by a metallopeptidase, as established with peptidase inhibitors. Ang II was liberated to about equal degrees by ACE and chymase-type enzymes. Cathepsin A's presence in heart tissue was also proven because it deamidated enkephalinamide substrate by immunoprecipitation of cathepsin A with antiserum to human recombinant enzyme and by immunohistochemistry. In immunohistochemistry, cathepsin A was detected in myocytes of atrial tissue. The products of Ang I cleavage, Ang 1-9 and Ang 1-7, potentiated the effect of an ACE-resistant bradykinin analog and enhanced kinin effect on the B 2 receptor in Chinese hamster ovary cells transfected to express human ACE and B 2 (CHO/AB), and in human pulmonary arterial endothelial cells. Ang 1-9 and 1-7 augmented arachidonic acid and nitric oxide (NO) release by kinin. Direct assay of NO liberation by bradykinin from endothelial cells was potentiated at 10 nmol/L concentration, 2.4-fold (Ang 1-9) and 2.1-fold (Ang 1-7); in higher concentrations, Ang 1-9 was significantly more active than Ang 1-7. Both peptides had traces of activity in the absence of bradykinin. Ang 1-9 and Ang 1-7 potentiated bradykinin action on the B 2 receptor by raising arachidonic acid and NO release at much lower concentrations than their 50% inhibition concentrations (IC 50 s) with ACE.

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Angiotensin converting enzyme inhibition in patients with congestive heart failure.

Cited by 211 publications

References 33 publications

Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors.

Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors.

Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression

Angiotensin 1-9 and 1-7 Release in Human Heart

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