Cardiomyocyte Apoptosis and Cardiac Angiotensin-Converting Enzyme in Spontaneously Hypertensive Rats

Dı́ez, Javier; Panizo, Ángel; Hernández, Marta; Vega, Francisco Fernández de; Sola, Iosu; Fortuño, María Antonia; Pardo, Javier

doi:10.1161/01.hyp.30.5.1029

Cited by 106 publications

(77 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous results from our laboratory showed that cardiomyocyte apoptosis is higher in the hypertrophied left ventricle of SHR at 30 weeks than at 16 weeks of age, although systolic and diastolic blood pressure values were similar at the 2 ages. 17 Similar findings analyzing the time course of cardiomyocyte apoptosis in SHR 18 and comparing aged SHR with and without heart failure 20 have recently been reported. All these data demonstrate that no clear association exists between cardiomyocyte apoptosis and blood pressure values in genetic hypertension.…”

Section: Mechanical Stresssupporting

confidence: 73%

“…We have previously reported that the increment of cardiomyocyte apoptosis in the hypertrophied left ventricle of adult SHR is associated in a temporal way with cardiac ACE activity and that a direct correlation exists between the 2 parameters in hypertensive animals. 17 Moreover, chronic treatment with either an ACE inhibitor or an angiotensin type 1 receptor (AT 1 ) antagonist prevents cardiomyocyte apoptosis in this model, 17,21,22 suggesting that the local renin-angiotensin system activation may be involved in the triggering of cardiomyocyte apoptosis. In this respect, it has been demonstrated that binding of angiotensin II to its AT 1 receptor induces apoptosis of cardiomyocytes isolated from neonatal 23 and adult 24 normotensive rats.…”

Section: Angiotensin IImentioning

confidence: 87%

“…14 In contrast, in genetic models of hypertension, mechanical stress is not the most important inductor of apoptosis since cardiomyocyte apoptosis has been shown to be a phenomenon independent of blood pressure values. [15][16][17][18] Alterations of cardiac apoptosis have been reported in newborn, young, adult, and aged spontaneously hypertensive rats (SHR) with and without heart failure. Compared with aged-matched normotensive Wistar-Kyoto rats (WKY), Schematic representation of the 2 alternative cardiomyocyte responses (A) that underlie the morphological alterations (B) present in hypertensive heart disease.…”

Section: Mechanical Stressmentioning

confidence: 99%

See 2 more Smart Citations

Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension

et al. 2001

Self Cite

View full text Add to dashboard Cite

Abstract-Hypertensive heart disease is a progressive condition in which the compensatory left ventricular hypertrophy that maintains cardiac output leads to myocardial remodeling, characterized by fibrosis, insufficient vascularization, and alterations in cardiomyocytes, including contractile disturbances, changes in gene expression, and decrease in the number of cells. Structural abnormalities in the myocardial wall accelerate the development of diastolic and systolic dysfunction, resulting in heart failure. Many observations point to the apoptotic cell death of cardiomyocytes as a relevant factor in the transition from compensatory hypertrophy to pump failure in experimental and human hypertension. Potential inducers of cardiomyocyte apoptosis in overloaded hearts include extrinsic factors, such as mechanical forces, neurohormonal activation, oxidative stress, hypoxia, and cytokines. Some lines of evidence indicate that angiotensin II and the overstretching of cardiomyocytes are originally involved in the triggering of apoptosis in hypertension, whereas other factors are being investigated. Furthermore, intracellular changes, such as downregulation of survival proteins or activation of death proteins, seem to play an important role. The assumption that the apoptosis of cardiomyocytes worsens hypertensive heart disease prognosis brings forth new approaches to avoid or slow the transition to pump failure. In this respect, experimental data indicate that currently used antihypertensive drugs interfere with cardiomyocyte apoptosis. Moreover, the knowledge of intracellular apoptotic processes in cardiomyocytes provides novel therapeutic strategies to be added to the multimodal approach in the prevention of heart failure.

show abstract

Section: Mechanical Stresssupporting

confidence: 73%

Section: Angiotensin IImentioning

confidence: 87%

Section: Mechanical Stressmentioning

confidence: 99%

See 1 more Smart Citation

Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension

et al. 2001

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cardiomyocyte apoptosis has been reported to be induced in vitro by the stimulus of Ang II added to the medium 17 or by mechanical stretch. 19 It has been shown that Ang II is involved in the induction of cardiomyocyte apoptosis in vivo in failing hearts such as those in aged (30 weeks old) spontaneously hypertensive rats 13,28 or in dogs that underwent cardiac pacing for over 3 months during which the apoptosis was inhibited by an AT 1 R antagonist 16 or an ACE inhibitor. 13,14 In the present study, however, the number of apoptotic cardiomyocytes in WT mice was not significantly increased by administration of Ang II over a period of 1 month at maximum.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis Is Not Increased in Myocardium Overexpressing Type 2 Angiotensin II Receptor in Transgenic Mice

et al. 2001

View full text Add to dashboard Cite

Abstract-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 ␣-myosin heavy-chain promoter. Ten-to 12-week-old male homozygous transgenic mice (nϭ44) and wild-type mice (nϭ44) were used. Both transgenic and wild-type mice were given either saline (control), a subpressor dose of angiotensin II (100 ng · kg Ϫ1 · min Ϫ1), a pressor dose of angiotensin II (1000 ng · kg Ϫ1 · min Ϫ1) for 14 days, a pressor 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 II (1000 ng · kg Ϫ1 · min Ϫ1) 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 II, 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 pressor dose of angiotensin II 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 Ϸ0 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 II 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. A ngiotensin (Ang) II has 2 major receptor isoforms: Ang II type 1 receptor (AT 1 R) and Ang II type 2 receptor (AT 2 R). Most of the well-known Ang II functions, such as increasing blood pressure, stimulating myocyte hypertrophy, and the proliferating effect in the cardiovascular system, are mediated by AT 1 R. 1-3 On the other hand, AT 2 R has been implicated in the inhibition of cell growth 4 and proliferation. 5 AT 2 R has been shown to mediate induction of apoptosis in the PC12 cell line, 6 vascular smooth muscle cells, 7 vascular endothelium, 8 fibroblasts, 9 granulose cells in the rat ovary, 10 neurons from the rat brain, 11 and human fetal adrenal cells. 12 Recently, it has been reported that cardiac remodeling in various heart diseases involves a loss of cardiomyocytes due to apoptosis [13][14][15] and that Ang II stimul...

show abstract

“…Medical treatment did not significantly differ between patients with and without elevated cTnT in the present study. Experimental studies have shown that the long-term administration of an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) prevents cardiomyocyte apoptosis in spontaneously hypertensive rats, 32,33) which suggests that either ACE-I or ARB can suppress ongoing myocardial damage. Further investigation is required to determine the mechanism of ongoing myocardial damage and its treatment in hypertensive patients.…”

Section: Therapeutic Implications Of Ongoing Myocardial Damage In Hy-mentioning

confidence: 99%

Elevated Cardiac Troponin T Predicts Adverse Outcomes in Hypertensive Patients

et al. 2011

View full text Add to dashboard Cite

SummaryOngoing myocardial damage detected as elevated serum cardiac troponin T (cTnT) indicates increased risk for future cardiac events in patients with chronic heart failure. Whether elevated cTnT is associated with adverse outcomes in patients with hypertension (HT) without left ventricular (LV) systolic dysfunction is unknown.We measured cTnT levels in 176 patients with essential HT without LV systolic dysfunction (LV ejection fraction ≤ 55%), renal failure, and prior cardiovascular or cerebrovascular diseases and 39 normal controls. Levels of cTnT were elevated ( ≥ 0.02 ng/mL) in 15 (9%) of the 176 patients and in 0 (0%) of the 39 normal controls (P = 0.04). The rate of diabetes mellitus (DM), the cardiothoracic ratio, plasma B-type natriuretic peptide (BNP) value, and LV mass index were significantly higher in patients with than without elevated cTnT (DM, 8/15 versus 29/161, P = 0.004; cardiothoracic ratio, 54.5 ± 4.5 versus 51.6 ± 5.2%, P = 0.04; BNP, 103.3 ± 142.3 versus 36.9 ± 50.7 pg/mL, P = 0.04; LV mass index, 227 ± 87 versus 152 ± 57 g/m 2 , P = 0.0001). Kaplan-Meier analysis demonstrated that significantly fewer (P < 0.000001) patients with, than without elevated cTnT remained free of events (hospitalization due to cardiovascular or cerebrovascular disease, n = 34). Stepwise Cox multivariate analysis revealed that elevated cTnT (hazard ratio, 6.58; P = 0.000001) and smoking (hazard ratio, 2.24; P = 0.04) were independent predictors of events.The present findings indicate that cTnT is a novel and useful predictor of future cardiovascular or cerebrovascular events in hypertensive patients. (Int Heart J 2011; 52: 164-169)

show abstract

Cardiomyocyte Apoptosis and Cardiac Angiotensin-Converting Enzyme in Spontaneously Hypertensive Rats

Cited by 106 publications

References 41 publications

Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension

Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension

Apoptosis Is Not Increased in Myocardium Overexpressing Type 2 Angiotensin II Receptor in Transgenic Mice

Elevated Cardiac Troponin T Predicts Adverse Outcomes in Hypertensive Patients

Contact Info

Product

Resources

About