Differential effects of isoproterenol on the activity of angiotensin-converting enzyme in the rat heart and aorta

Cunha, Valdeci da; Cicilini, Maria Aparecida; Mill, José Geraldo

doi:10.1590/s0100-879x1999000300017

Cited by 14 publications

(9 citation statements)

References 15 publications

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“…Davel et al b-adrenoceptors change endothelial function end diastolic pressures, mean arterial pressure, heart rate or body weight (Vassallo et al, 1988;Busatto et al, 1999). These results suggest that the treatment used in the present study did not produce cardiac failure.…”

Section: Discussionsupporting

confidence: 54%

Changes in vascular reactivity following administration of isoproterenol for 1 week: a role for endothelial modulation

Davel¹,

Kawamoto²,

Scavone³

et al. 2006

British J Pharmacology

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1 The aim of this study was to assess the effects of treatment with isoproterenol (ISO, 0.3 mg kg À1 day À1 , s.c.) for 7 days on the vascular reactivity of rat-isolated aortic rings. Additionally, potential mechanisms underlying the changes that involved the endothelial modulation of contractility were investigated. 2 Treatment with ISO induced cardiac hypertrophy without changes in haemodynamic parameters. Aortic rings from ISO-treated rats showed an increase in the contraction response to phenylephrine (PHE) and serotonin, but did not change relaxations produced by acetylcholine or isoproterenol. Removal of the endothelium increased the responses to PHE in both groups. However, this procedure was less effective in ISO-treated as compared with control rats. Endothelial cell removal abolished the increase in the response to PHE in ISO-treated rats. The presence of N o -nitro-L-arginine methyl ester shifted the concentration-response curve to PHE to the left in both groups of rats. However, this effect was more pronounced in the ISO group. In addition, aminoguanidine (50 mM) potentiated the actions of PHE only in the ISO group. ISO treatment increased nitric oxide synthase (NOS) activity and neuronal NOS and endothelial NOS protein expression in the aorta. 3 Neither losartan (10 mM) nor indomethacin (10 mM) abolished the effects of ISO on the actions of PHE. Superoxide dismutase (SOD, 150 U ml À1 ) and L-arginine (5 mM), but neither catalase (300 U ml À1 ) nor apocynin (100 mM), blocked the effect of ISO treatment. In addition, we observed an increase in superoxide anion levels as measured by ethidium bromide fluorescence and of copper and zinc superoxide dismutase protein expression in ISO-treated rats. 4 In conclusion, our data suggest that ISO treatment alters the endothelial cell-mediated modulation of the contraction to PHE in rat aorta. The increased maximal response of PHE seems to be due to an increase in superoxide anion generation, which inactivates some of the basal NO produced and counteracts NO-mediated negative modulation even in the presence of high NO production and antioxidant defence.

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Section: Discussionsupporting

confidence: 54%

Changes in vascular reactivity following administration of isoproterenol for 1 week: a role for endothelial modulation

Davel¹,

Kawamoto²,

Scavone³

et al. 2006

British J Pharmacology

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“…It has been previously demonstrated that ␤-AR stimulation leads to cardiac hypertrophy, which is related to induction of local RAS (5,16,18). In fact, independent cardiac RAS (10,22) with all RAS components locally expressed (11,22,32) makes RAS more efficient to couple with adrenergic activation.…”

Section: Discussionmentioning

confidence: 99%

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Ferreira

Bacurau²,

Evangelista³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Sympathetic hyperactivity (SH) and renin angiotensin system (RAS) activation are commonly associated with heart failure (HF), even though the relative contribution of these factors to the cardiac derangement is less understood. The role of SH on RAS components and its consequences for the HF were investigated in mice lacking alpha(2A) and alpha(2C) adrenoceptor knockout (alpha(2A)/alpha(2C)ARKO) that present SH with evidence of HF by 7 mo of age. Cardiac and systemic RAS components and plasma norepinephrine (PN) levels were evaluated in male adult mice at 3 and 7 mo of age. In addition, cardiac morphometric analysis, collagen content, exercise tolerance, and hemodynamic assessments were made. At 3 mo, alpha(2A)/alpha(2C)ARKO mice showed no signs of HF, while displaying elevated PN, activation of local and systemic RAS components, and increased cardiomyocyte width (16%) compared with wild-type mice (WT). In contrast, at 7 mo, alpha(2A)/alpha(2C)ARKO mice presented clear signs of HF accompanied only by cardiac activation of angiotensinogen and ANG II levels and increased collagen content (twofold). Consistent with this local activation of RAS, 8 wk of ANG II AT(1) receptor blocker treatment restored cardiac structure and function comparable to the WT. Collectively, these data provide direct evidence that cardiac RAS activation plays a major role underlying the structural and functional abnormalities associated with a genetic SH-induced HF in mice.

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“…Similarly, nebivolol improved diastolic dysfunction and myocardial remodeling associated with insulin resistance in the Zucker obese rats by reducing cardiac oxidative stress [13]. Although β1-adrenergic receptor stimulation up-regulates angiotensin-converting enzyme (ACE) in isolated cardio-myocyte as well as in the heart of normotensive rats [14,15], no data exist regarding the effects of nebivolol on the cardiac RAS. Thus, to further investigate the potential beneficial cardiac effects of nebivolol, we tested the hypothesis that nebivolol improves salt-induced cardiac dysfunction and remodeling in SHRs by suppressing cardiac RAS and oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Nebivolol reduces cardiac angiotensin II, associated oxidative stress and fibrosis but not arterial pressure in salt-loaded spontaneously hypertensive rats

Varagić

Ahmad

VonCannon

et al. 2012

Journal of Hypertension

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Objectives Increased sympathetic outflow, renin–angiotensin system (RAS) activity, and oxidative stress are critical mechanisms underlying the adverse cardiovascular effects of dietary salt excess. Nebivolol is a third-generation, highly selective β1-receptor blocker with RAS-reducing effects and additional antioxidant properties. This study evaluated the hypothesis that nebivolol reduces salt-induced cardiac remodeling and dysfunction in spontaneous hypertensive rats (SHRs) by suppressing cardiac RAS and oxidative stress. Methods Male SHRs (8 weeks of age) were given an 8% high salt diet (HSD; n = 22), whereas their age-matched controls (n = 10) received standard chow. In a subgroup of HSD rats (n = 11), nebivolol was given at a dose of 10 mg/kg per day by gastric gavage. Results After 5 weeks, HSD exacerbated hypertension as well as increased left-ventricular weight and collagen deposition while impairing left-ventricular relaxation. Salt-induced cardiac remodeling and dysfunction were associated with increased plasma renin concentration (PRC), cardiac angiotensin II immunostaining, and angiotensin-converting enzyme (ACE)/ACE2 mRNA and activity ratio. HSD also increased cardiac 3-nitrotyrosine staining indicating enhanced oxidative stress. Nebivolol treatment did not alter the salt-induced increase in arterial pressure, left-ventricular weight, and cardiac dysfunction but reduced PRC, cardiac angiotensin II immunostaining, ACE/ACE2 ratio, oxidative stress, and fibrosis. Conclusions Our data suggest that nebivolol, in a blood pressure-independent manner, ameliorated cardiac oxidative stress and associated fibrosis in salt-loaded SHRs. The beneficial effects of nebivolol may be attributed, at least in part, to the decreased ACE/ACE2 ratio and consequent reduction of cardiac angiotensin II levels.

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Differential effects of isoproterenol on the activity of angiotensin-converting enzyme in the rat heart and aorta

Cited by 14 publications

References 15 publications

Changes in vascular reactivity following administration of isoproterenol for 1 week: a role for endothelial modulation

Changes in vascular reactivity following administration of isoproterenol for 1 week: a role for endothelial modulation

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Nebivolol reduces cardiac angiotensin II, associated oxidative stress and fibrosis but not arterial pressure in salt-loaded spontaneously hypertensive rats

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