Kinetics of cardiac and vascular remodeling by spontaneously hypertensive rats after discontinuation of long-term captopril treatment

Rocha, Wanize Almeida; Lunz, Wellington; Baldo, Marcelo Perim; Pimentel, Enildo Broetto; Dantas, Eduardo Miranda; Rodrigues, Sérgio Lamêgo; Mill, José Geraldo

doi:10.1590/s0100-879x2010007500023

Cited by 12 publications

(17 citation statements)

References 28 publications

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“…As a result, cardiac hypertrophy develops early and reaches a stable value around three months of age, remaining constant throughout the rest of the life of the animal 25,26. Our study shows that high salt intake increases cardiac hypertrophy in adult SHRs that had well-established blood pressure levels and compensatory cardiac hypertrophy compared to normotensive rats.…”

Section: Discussionmentioning

confidence: 55%

Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake

Baldo

Zaniqueli

Forechi

et al. 2011

Clinics

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OBJECTIVE:To evaluate the effect of spironolactone on ventricular stiffness in spontaneously hypertensive adult rats subjected to high salt intake.INTRODUCTION:High salt intake leads to cardiac hypertrophy, collagen accumulation and diastolic dysfunction. These effects are partially mediated by cardiac activation of the renin-angiotensin-aldosterone system.METHODS:Male spontaneously hypertensive rats (SHRs, 32 weeks) received drinking water (SHR), a 1% NaCl solution (SHR-Salt), or a 1% NaCl solution with a daily subcutaneous injection of spironolactone (80 mg.kg-1) (SHR-Salt-S). Age-matched normotensive Wistar rats were used as a control. Eight weeks later, the animals were anesthetized and catheterized to evaluate left ventricular and arterial blood pressure. After cardiac arrest, a double-lumen catheter was inserted into the left ventricle through the aorta to obtain in situ left ventricular pressure-volume curves.RESULTS:The blood pressures of all the SHR groups were similar to each other but were different from the normotensive controls (Wistar = 109±2; SHR = 118±2; SHR-Salt = 117±2; SHR-Salt-S = 116±2 mmHg; P<0.05). The cardiac hypertrophy observed in the SHR was enhanced by salt overload and abated by spironolactone (Wistar = 2.90±0.06; SHR = 3.44±0.07; SHR-Salt = 3.68±0.07; SHR-Salt-S = 3.46±0.05 mg/g; P<0.05). Myocardial relaxation, as evaluated by left ventricular dP/dt, was impaired by salt overload and improved by spironolactone (Wistar = -3698±92; SHR = -3729±125; SHR-Salt = -3342±80; SHR-Salt-S = -3647±104 mmHg/s; P<0.05). Ventricular stiffness was not altered by salt overload, but spironolactone treatment reduced the ventricular stiffness to levels observed in the normotensive controls (Wistar = 1.40±0.04; SHR = 1.60±0.05; SHR-Salt = 1.67±0.12; SHR-Salt-S = 1.45±0.03 mmHg/ml; P<0.05).CONCLUSION:Spironolactone reduces left ventricular hypertrophy secondary to high salt intake and ventricular stiffness in adult SHRs.

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Section: Discussionmentioning

confidence: 55%

Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake

Baldo

Zaniqueli

Forechi

et al. 2011

Clinics

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“…Our observations of the prevention of hypertension development and the progressive increase of BP after withdrawal are similar to those reported by others using different antihypertensives. Rocha et al (29) treated SHRs and WKY rats with captopril at 4 wk of age, and had the drug withdrawn at 14 wk. Direct BP taken via femoral artery catheters demonstrated that captopril prevented the development of hypertension; however, after it was withdrawn, mean arterial pressure returned to approximately similar levels but still remained significantly lower.…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic reticulum stress inhibition blunts the development of essential hypertension in the spontaneously hypertensive rat

Naiel

Carlisle

Lü

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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Essential hypertension is the leading cause of premature death worldwide. However, hypertension’s cause remains uncertain. endoplasmic reticulum (ER) stress has recently been associated with hypertension, but it is unclear whether ER stress causes hypertension. To clarify this question, we examined if ER stress occurs in blood vessels before the development of hypertension and if ER stress inhibition would prevent hypertension development. We used the spontaneously hypertensive rat (SHR) as a model of human essential hypertension and the Wistar-Kyoto (WKY) rat as its normotensive control. Resistance arteries collected from young rats determined that ER stress was present in SHR vessels before the onset of hypertension. To assess the effect of ER stress inhibition on hypertension development, another subset of rats were treated with 4-phenylbutyric acid (4-PBA; 1 g·kg−1·day−1) for 8 wk from 5 wk of age. Blood pressure was measured via radiotelemetry and compared with untreated SHR and WKY rats. Mesenteric resistance arteries were collected and assessed for structural and functional changes associated with hypertension. Systolic and diastolic blood pressures were significantly lower in the 4-PBA-treated SHR groups than in untreated SHRs. Additionally, 4-PBA significantly decreased the media-to-lumen ratio and ER stress marker expression, improved vasodilatory response, and reduced contractile responses in resistance arteries from SHRs. Overall, ER stress inhibition blunted the development of hypertension in the SHR. These data add evidence to the hypothesis that a component of hypertension in the SHR is caused by ER stress. NEW & NOTEWORTHY In this study, 4-phenylbutyric acid’s (4-PBA’s) molecular chaperone capability was used to inhibit endoplasmic reticulum (ER) stress in the small arteries of young spontaneously hypertensive rats (SHRs) and reduce their hypertension. These effects are likely mediated through 4-PBA's effects to reduce resistant artery contractility and increase nitric oxide-mediated endothelial vasodilation through a process preventing endothelial dysfunction. Overall, ER stress inhibition blunted the development of hypertension in this young SHR model. This suggests that a component of the increase in blood pressure found in SHRs is due to ER stress. However, it is important to note that inhibition of ER stress was not able to fully restore the blood pressure to normal, suggesting that a component of hypertension may not be due to ER stress. This study points to the inhibition of ER stress as an important new physiological pathway to lower blood pressure, where other known approaches may not achieve blood pressure-lowering targets.

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“…Moreover, when captopril was given early in life, significantly lower blood pressure levels persisted even 20 weeks after treatment withdrawal 5 and were associated with LV hypertrophy prevention and aortic remodeling reduction. 7 Sustained blood pressure reduction has been assumed to result from decreased sympathetic vasoconstriction and a major therapy-induced reduction of nifedipine-sensitive blood pressure in young SHRs. In addition, the withdrawal of captopril therapy induced enhanced vascular remodeling in aged but not in young SHRs despite equal doses and treatment duration.…”

Section: Discussionmentioning

confidence: 99%

“…Captopril and nifedipine are classical antihypertensive drugs, and their effects on SBP regulation and cardiovascular remodeling in SHRs are well-established. 5,7,9 The antihypertensive effects of these short-acting drugs have been found to be in the same range or even better than those reported from longacting angiotensin-converting enzyme inhibitors and calcium channel antagonists, such as enalapril, ramipril and felodipine. 10,23 Therapy with nifedipine alone was left out of our study because a preliminary study on young SHRs showed no antihypertensive effects with this treatment.…”

Section: Limitations Of the Studymentioning

confidence: 96%

“…6 Transient treatment with captopril during this phase was found to prevent the development of cardiac and vascular remodeling. 7 The aim of the present study was to analyze the long-term effects of hypertension and of antihypertensive treatment that is started late in life in aged SHRs. According to typical therapeutic regimens in humans, the effects of a monotherapy and a combination of two drugs should be examined.…”

Section: Introductionmentioning

confidence: 99%

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Effects of late-onset and long-term captopril and nifedipine treatment in aged spontaneously hypertensive rats: Echocardiographic studies

Zimmer

Hawlitschek

Rabald³

et al. 2015

Hypertens Res

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The purpose of the present study was to analyze the changes in blood pressure, left ventricular (LV) wall thickness and LV systolic function of aged spontaneously hypertensive rats (SHRs) either with or without antihypertensive therapy. Twenty-one SHRs aged 60.5±0.25 weeks were investigated over 22 weeks. They were divided into the following three groups (7 per group): untreated controls (CTRL), treatment with captopril (CAP, 60 mg kg(-1) daily) and treatment with captopril plus nifedipine (CAP+NIF, 60+10 mg kg(-1) daily). Systolic blood pressure (SBP) was regularly measured using the tail cuff method, and an echocardiogram was repeatedly obtained to examine the LV systolic and diastolic area, LV systolic fractional area change, cardiac output and LV myocardial wall thickness. Finally, heart catheterization was performed. While SBP remained stable in the CTRL animals over the experimental period, both of the antihypertensive treatments significantly reduced SBP by 20% in the treated animals (P<0.001). Echocardiography demonstrated that both the systolic and the diastolic LV function of the untreated SHRs deteriorated over time, whereas both types of antihypertensive treatments attenuated and delayed but did not completely prevent the decline in LV systolic function. Cardiac output, as determined by pulsed wave Doppler echocardiography, remained significantly higher in the treated animals than in CTRLs until week 20, but it then decreased. Heart catheterization showed a significant decrease in LV function, as reflected by the LV systolic pressure and contractility, in the CTRLs but not in treated animals. These findings clearly indicate that late-onset antihypertensive treatment with CAP or CAP+NIF is beneficial with respect to blood pressure reduction, LV hypertrophy attenuation and LV systolic function preservation.

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Kinetics of cardiac and vascular remodeling by spontaneously hypertensive rats after discontinuation of long-term captopril treatment

Cited by 12 publications

References 28 publications

Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake

Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake

Endoplasmic reticulum stress inhibition blunts the development of essential hypertension in the spontaneously hypertensive rat

Effects of late-onset and long-term captopril and nifedipine treatment in aged spontaneously hypertensive rats: Echocardiographic studies

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