Chronic effects of an endothelin-converting enzyme inhibitor on cardiorenal and hormonal function in heart failure

Endothelin (ET)-converting enzyme (ECE) is a rate-limiting step in ET-1 generation, and its expression and activity are increased significantly with the development of congestive heart failure (CHF). The selective enzymic inhibition of ET-1 formation thus seems to be a very important target in the prevention of CHF. We evaluated the chronic effects of a specific ECE inhibitor, FR901533 (0.3mg·kg-1·h-1, n = 5) on cardiac, hormonal, and body fluid balance in dogs with CHF induced by rapid right ventricular pacing (270beats/min, 22 days). Vehicle dogs were given placebo (n = 5). Despite no significant difference in blood pressure, FR901533 decreased pulmonary capillary wedge pressure and increased cardiac output compared with the vehicle. FR901533 prevented the reduction of urine flow rate and urinary sodium excretion in association with an increase in the glomerular filtration rate and renal plasma flow compared with the vehicle. FR901533 also suppressed significantly the elevation of plasma atrial natriuretic peptide and aldosterone levels which is an established prognostic factor in CHF. These results indicate that the role of ECE in CHF is important and that chronic ECE inhibition could possess therapeutic potential in the treatment of CHF not only on haemodynamics but also in the prevention of fluid retention.

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Increased cardiomyocyte apoptosis during the transition to heart failure in the spontaneously hypertensive rat

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.272.5.h2313 ◽

1997 ◽

Vol 272 (5) ◽

pp. H2313-H2319 ◽

Cited By ~ 32

Author(s):

Z. Li ◽

O. H. Bing ◽

X. Long ◽

K. G. Robinson ◽

E. G. Lakatta

Keyword(s):

Heart Failure ◽

Angiotensin Converting Enzyme ◽

Angiotensin Converting Enzyme Inhibitor ◽

Enzyme Inhibitor ◽

Apoptotic Cells ◽

Mrna Levels ◽

Converting Enzyme ◽

Spontaneously Hypertensive ◽

Converting Enzyme Inhibitor ◽

Significant Difference

The transition from compensated hypertrophy to failure in spontaneously hypertensive rats (SHR) of advanced age is associated with a marked increase in collagen, a reduction in myocyte mass, and a reduction in maximum Ca(2+)-activated myofibrillar force. We hypothesized that the reduction in myocyte mass and associated functional loss may be due to increased cell death by apoptosis. To test this hypothesis, we studied hearts from failing (SHR-F) and nonfailing SHR (SHR-NF) and age-matched Wistar-Kyoto rats (WKY). In addition, hearts from SHR-F that had been treated with an angiotensin-converting enzyme inhibitor (captopril) for an average of 27 days were also studied. Apoptotic cells were quantified in cross sections of myocardium by the terminal deoxynucleotidyltransferase- mediated 2'-deoxyuridine 5'-triphosphate nick end labeling technique. To identify the type of the cells undergoing apoptosis, sections were also stained for alpha-sarcomeric actin. Apoptotic cells were significantly increased in the SHR-F (38.92 +/- 12.79 vs. 8.05 +/- 3.98 cells/100,000 nuclei in SHR-NF; P < 0.05 and vs. 2.21 +/- 1.4 cells/100,000 nuclei in WKY; P < 0.01). Captopril treatment of SHR-F reduced the number of apoptotic cells to the level in SHR-NF (9.17 +/- 1.53 cells/100,000 nuclei; P < 0.01 vs. SHR-F). Most apoptotic cells were of cardiac myocyte origin. There was no significant difference in Bcl-2 protein expressed by hearts among the three groups. WAF-1 mRNA levels were increased in both SHR groups vs. WKY; in SHR-F, the density of WAF-1 mRNA was higher than in SHR-NF. Thus increased numbers of apoptotic cells are present in failing SHR hearts, suggesting that apoptosis might be a mechanism involved in the reduction of myocyte mass that accompanies the transition from stable compensation to heart failure in this model. Administration of the angiotensin-converting enzyme inhibitor captopril, which ameliorates heart failure in this model, is associated with a reduction in the exaggerated apoptosis that accompanies heart failure.

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Urocortin 2 combined with angiotensin-converting enzyme inhibition in experimental heart failure

Clinical Science ◽

10.1042/cs20070364 ◽

2008 ◽

Vol 114 (10) ◽

pp. 635-642 ◽

Cited By ~ 22

Author(s):

Miriam T. Rademaker ◽

Christopher J. Charles ◽

M. Gary Nicholls ◽

A. Mark Richards

Keyword(s):

Heart Failure ◽

Angiotensin Converting Enzyme ◽

Enzyme Inhibitor ◽

Therapeutic Potential ◽

Combined Treatment ◽

Peripheral Resistance ◽

Plasma Renin ◽

Renin Activity ◽

Angiotensin Converting Enzyme Inhibition ◽

Converting Enzyme

Ucn2 (urocortin 2) is a recently discovered peptide with therapeutic potential in heart failure. As any new treatment is likely to be used in conjunction with standard ACEI (angiotensin-converting enzyme inhibitor) therapy, it is important that the combined effects of these agents are assessed. In the present study, we investigated the effects of Ucn2 and an ACEI (captopril) administered for 3 h, both separately and together, in eight sheep with pacing-induced heart failure. Ucn2 and captopril alone both increased CO (cardiac output; Ucn2>captopril) and decreased arterial pressure (captopril>Ucn2), left atrial pressure (Ucn2>captopril) and peripheral resistance (Ucn2=captopril) relative to controls. Compared with either treatment alone, combined treatment further improved CO and reduced peripheral resistance and cardiac preload, without inducing further falls in blood pressure. In contrast with the marked increase in plasma renin activity observed with captopril alone, Ucn2 administration reduced renin activity, whereas the combined agents resulted in intermediate renin levels. All active treatments decreased circulating levels of aldosterone (Ucn2+captopril>Ucn2=captopril), endothelin-1 and the natriuretic peptides (Ucn2+captopril=Ucn2>captopril), whereas adrenaline (epinephrine) fell only with Ucn2 (Ucn2+captopril=Ucn2), and vasopressin increased during captopril alone. Ucn2, both separately and in conjunction with captopril, increased urine output, sodium and creatinine excretion and creatinine clearance. Conversely, captopril administered alone adversely affected these renal indices. In conclusion, co-treatment with Ucn2 and an ACEI in heart failure produced significantly greater improvements in haemodynamics, hormonal profile and renal function than achieved by captopril alone. These results indicate that dual treatment with these two agents is beneficial.

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PREVALENSI ANEMIA PADA PASIEN GAGAL JANTUNG DI RSUP PROF. DR. R. D. KANDOU MANADO PERIODE 2013

e-CliniC ◽

10.35790/ecl.3.1.2015.6748 ◽

2015 ◽

Vol 3 (1) ◽

Author(s):

Aaron Ch. Rambi ◽

Linda W. A. Rotty ◽

Agnes L. Panda

Keyword(s):

Heart Failure ◽

Angiotensin Converting Enzyme ◽

Enzyme Inhibitor ◽

Age Groups ◽

Severe Congestive Heart Failure ◽

Converting Enzyme ◽

Converting Enzyme Inhibitors ◽

Heart Failure Patients ◽

Significant Difference ◽

Prevalence Of Anemia

Abstract: Anemia is common in heart failure patients, especially in patients with old age, female, chronic kidney disease, ACE inhibitors (angiotensin-converting-enzyme inhibitors) users and in patients with severe congestive heart failure. Anemia is an independent prognostic factor for mortality. Anemia is characterized by the value of hemoglobin less than 13 g / dl in men and less than 12 g / dl in women. The purpose of this study was to determine the prevalence of anemia in patients with heart failure. This was a descriptive retrospective study. The samples of this study were 834 medical records of hospitalization and ambulatory patients in RSUP Prof. Dr. R. D. Kandou Manado which had hematology examination results in 2013. The results showed that the prevalence of anemia in heart failure patients was 33.6% and mostly were mild anemia (57%). Although not so significant, the proportion of female patients with anemia were higher (33,57%) than male (33,54%). The over 64 years group has the highest proportion of all age groups. Conclusion: Anemia is common in heart failure patients, especially those aged over 64 years. There was no significant difference between the proportion of women and men who were anemic. Most patients suffered from mild anemia.Keywords: anemia, heart failure, prevalenceAbstrak: Anemia sering ditemukan pada gagal jantung terutama pada pasien yang berusia tua, dengan jenis kelamin perempuan, menderita kelainan ginjal kronik, pengguna ACE inhibitor (angiotensin-converting-enzyme inhibitor) dan pada pasien dengan gagal jantung kongestif yang parah. Anemia merupakan faktor prognostik independen terhadap kematian. Anemia ditandai dengan nilai hemoglobin kurang dari 13 g/dl pada laki-laki dan kurang dari 12 g/dl pada perempuan. Tujuan penelitian ini adalah untuk mengetahui prevalensi anemia pada pasien gagal jantung. Penelitian ini bersifat deskriptif retrospektif. Sampel penelitian ini adalah 834 rekam medis pasien rawat inap dan rawat jalan di RSUP Prof. Dr. R. D. Kandou Manado yang memiliki hasil pemeriksaan hematologi. Hasail penelitian menunjukkan bahwa prevalensi anemia pada pasien gagal jantung adalah 33,6% dan sebagian besar menderita anemia ringan (57%). Walaupun tidak begitu signifikan, proporsi dari pasien perempuan dengan anemia lebih tinggi (33,57%) dibandingkan pria (33,54%). Kelompok umur lebih dari 64 thun memiliki proporsi tertinggi dibadingkan semua kelompok umur. Simpulan: Anemia sering ditemukan pada pasien gagal jantung, terutama yang berusia lebih dari 64 tahun. Tidak ada perbedaan yang signifikan antara proporsi dari peremuan dan laki-laki yang menderita anemia. Kebanyakan pasien menderita anemia ringan.Kata kunci: anemia, gagal jantung, prevalensi

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