Angiotensin II-dependent vascular alterations in young cardiomyopathic hamsters: Role for oxidative stress

Escobales, Nelson; Crespo, Marı́a J.

doi:10.1016/j.vph.2005.09.008

Cited by 21 publications

(36 citation statements)

References 31 publications

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“…Alterations include endothelial dysfunction, increased contractile response to Ang II, and increased vascular ACE and NADPH oxidase activities. [30][31][32][33][34] These changes suggest that RAS is altered from the earliest stages in the Bio-TO2 cardiomyopathic animals. Despite vascular abnormalities, cardiac output (CO) is preserved in 2-month-old SCH, 34 although it decreases significantly at 6 months of age.…”

Section: Discussionmentioning

confidence: 97%

Enalapril and Losartan Are More Effective Than Carvedilol in Preventing Dilated Cardiomyopathy in the Syrian Cardiomyopathic Hamster

Crespo

Cruz

Altieri

et al. 2008

J Cardiovasc Pharmacol Ther

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To assess the role of the renin-angiotensin (RAS) and adrenergic systems in the development and progression of dilated cardiomyopathy in the Syrian cardiomyopathic hamster (SCH), echocardiographic parameters were evaluated in 6-month-old animals after 5 months of treatment with enalapril (25 mg/kg/day) plus losartan (10 mg/kg/day), or with carvedilol (1 mg/kg/day). Cardiac output indexes (COI) increased by 53% after RAS blockade and by 20% after beta-blockade in SCH. Moreover, LVEDV and LVESV decreased 30% and 62%, respectively (P < .05) during RAS blockade, whereas ejection fraction (EF) increased by 48%. By contrast, carvedilol reduced LVESV by only 28% (P < .05) and increased EF by only 15% (P < .05). These results suggest that RAS activation plays a critical role in the development of cardiac dysfunction in SCH and that suppression of RAS may be more effective than beta-blockade in retarding the development of cardiomyopathy in SCH. Owing to timing (pre-heart failure stage) and to the single dose protocol, the implications of this study for human subjects remain to be clarified.

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Section: Discussionmentioning

confidence: 97%

Enalapril and Losartan Are More Effective Than Carvedilol in Preventing Dilated Cardiomyopathy in the Syrian Cardiomyopathic Hamster

Crespo

Cruz

Altieri

et al. 2008

J Cardiovasc Pharmacol Ther

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“…Another possible mechanism by which carotid IMT is decreased in the ARB group may be decreased vascular oxidative stress. Oxidative stress has been known to damage vessel walls and to be a cause of atherosclerosis (7,8). It has been reported that the activation of AT1 receptors leads to the release of vascular superoxide (25).…”

Section: Discussionmentioning

confidence: 99%

Candesartan Decreases Carotid Intima-Media Thickness by Enhancing Nitric Oxide and Decreasing Oxidative Stress in Patients with Hypertension

Ono¹,

Minatoguchi

Watanabe³

et al. 2008

Hypertens Res

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Candesartan has been reported to produce nitric oxide (NO) and to decrease oxidative stress in animal studies. We investigated candesartan's effect on the production of NO and oxidative stress as well as on carotid intima-media thickness (IMT) in hypertensive patients. One-hundred age-matched hypertensive patients were enrolled into an angiotensin II receptor blocker (ARB) group (n =50) or a non-ARB group (n =50). The ARB group was treated with candesartan 8 mg and, when needed, Ca channel blockers, angiotesin-converting enzyme (ACE) inhibitors, and/or -blockers. The non-ARB group was treated with drugs other than ARB.

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“…In addition, our results reveal that carvedilol does not depress or modify normal cardiac function when administered to SCH between 1 and 2 months of age. The peripheral vasodilator activity of carvedilol may be involved in the maintenance of cardiac function in 2-month-old SCH, which is known to be normal at this age [28] , possibly by counteracting the negative inotropic effects of ␤ 1 -and ␤ 2 -receptor blockade and the vasoconstrictor effects of vascular ␤ 2 -receptor blockade [36] .…”

Section: Discussionmentioning

confidence: 99%

“…Our group has reported significant vascular alterations in 2-month-old SCH that have not yet developed the clinical manifestations of HF [24][25][26][27][28] . These alterations include increased contractile response to Ang II and angiotensin-converting enzyme activity in the aorta, and impaired vasorelaxation in response to acetylcholine in norepinephrine-precontracted aortic rings.…”

mentioning

confidence: 88%

“…These alterations include increased contractile response to Ang II and angiotensin-converting enzyme activity in the aorta, and impaired vasorelaxation in response to acetylcholine in norepinephrine-precontracted aortic rings. Despite these vascular abnormalities, cardiac function in 2-month-old SCH, as determined by echocardiography, is normal [28] . The present study assessed the effects of carvedilol on the cardiovascular status of 2-and 6-month-old SCH.…”

mentioning

confidence: 95%

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Chronic Administration of Carvedilol Improves Cardiac Function in 6-Month-Old Syrian Cardiomyopathic Hamsters

Cruz

Arocho²,

Brás-Rosário³

et al. 2007

Pharmacology

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Heart failure (HF) is a multifactorial and progressive disease that has been linked to activation of the renin-angiotensin and sympathetic systems. In recent years, β-blockers have been shown to improve the status of HF patients, although the precise mechanisms remain unclear. The present study evaluates the effect of β-blockade with carvedilol (1 mg/kg/day) on cardiovascular function in 2- and 6-month-old cardiomyopathic hamsters (SCH) after 1-month and 5-month treatment periods with the drug, respectively. Age-matched golden hamsters were used as controls (CT). Systolic blood pressure (SBP) and echocardiographic studies were evaluated. The latter studies included left ventricular end-systolic (LVESV) and end-diastolic (LVEDV) volumes, ejection fraction (EF), cardiac output index (COI), heart rate (HR), and left ventricular posterior wall thickness (LVPWT). In 2-month-old SCH, carvedilol administration during a 1-month period reduced SBP from 107.59 ± 3.49 to 77.26 ± 3.49 mm Hg (n = 5, p < 0.05). At this stage, cardiac parameters in SCH were similar to those of controls and were not affected by carvedilol administration. In 6-month-old SCH, 5-month administration of carvedilol decreased SBP from 102.16 ± 3.61 to 90.60 ± 2.80 mm Hg (n = 5, p < 0.05), HR from 363 ± 14 to 324 ± 14 bpm (n = 5, p < 0.05), and LVESV from 0.18 ± 0.01 to 0.13 ± 0.01 ml/100 g BW (n = 5, p < 0.05), and increased EF and COI by 14 and 23%, respectively (n = 5, p < 0.05). The drug did not modify LVEDV or LVPWT. These results reveal that carvedilol significantly improves cardiac function in 6-month-old cardiomyopathic hamsters, but it does not prevent ventricular dilatation. Improved cardiac function appears to be secondary to decreased total peripheral resistance, due mainly to the vasodilator properties of the drug. Thus, overactivation of the sympathetic system is not likely to be a determining factor in the etiology of dilated cardiomyopathy in this animal model.

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Angiotensin II-dependent vascular alterations in young cardiomyopathic hamsters: Role for oxidative stress

Cited by 21 publications

References 31 publications

Enalapril and Losartan Are More Effective Than Carvedilol in Preventing Dilated Cardiomyopathy in the Syrian Cardiomyopathic Hamster

Enalapril and Losartan Are More Effective Than Carvedilol in Preventing Dilated Cardiomyopathy in the Syrian Cardiomyopathic Hamster

Candesartan Decreases Carotid Intima-Media Thickness by Enhancing Nitric Oxide and Decreasing Oxidative Stress in Patients with Hypertension

Chronic Administration of Carvedilol Improves Cardiac Function in 6-Month-Old Syrian Cardiomyopathic Hamsters

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