Different Effects on Inhibition of Cardiac Hypertrophy in Spontaneously Hypertensive Rats by Monotherapy and Combination Therapy of Adrenergic Receptor Antagonists and/or the Angiotensin II Type 1 Receptor Blocker under Comparable Blood Pressure Reduction

Asai, Takae; Kushiro, Toshio; Fujita, Hirotaka; Kanmatsuse, Katsuo

doi:10.1291/hypres.28.79

Cited by 19 publications

(24 citation statements)

References 38 publications

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“…Based on this consideration, we examined the effect of various antihypertensive treatments on cardiac hypertrophy. antihypertensives have been reported to have an effect on cardiac hypertrophy in SHr (32,33). in this study, there were no significant differences between the corrected heart and lV weights; the level of cardiac hypertrophy prevention in the treatment groups was almost the same.…”

Section: Bsupporting

confidence: 39%

Combination therapy based on the angiotensin receptor blocker olmesartan for vascular protection in spontaneously hypertensive rats

Tomita¹

2009

Mol Med Rep

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Abstract. For hypertension, combination therapies are recommended to acheive a low target blood pressure. in this study, the efficacy of combination therapies for preventing organ damage was investigated in spontaneously hypertensive rats (SHr). Twenty-week-old male SHr were orally administered olmesartan (Olm) (5 mg/kg/day) for the first 4 weeks. Subsequently, rats were randomly divided into 5 groups and administered add-on drugs for another 4 weeks as follows: olm+olm (5 mg/kg/day), olm+azelnidipine (aze) (30 mg/kg/ day), olm+temocapril (Tem) (10 mg/kg/day), olm+atenolol (ate) (5 mg/kg/day), olm+hydrochlorothiazide (HcTZ) (5 mg/kg/ day). Blood pressure and heart rate were measured at weeks 0, 4 and 8 by the tail-cuff method. Heart and kidney weights were determined, and endothelial function was assessed by evaluating the dilator response to acetylcholine. in comparison to untreated control SHR, a significant reduction in systolic blood pressure was observed at weeks 4 and 8 in all groups (p<0.05), while heart rate was significantly reduced at week 8 in only the olm+aze and olm+ate groups (p<0.05). in all groups, heart but not kidney weight was significantly decreased (p<0.05), and endothelial function was significantly improved (p<0.05) compared to the control SHr. in the olm+olm, olm+Tem and olm+aze groups, endothelial function was significantly improved as compared to the other treatment groups (p<0.05). Thus, when using an angiotensin receptor blocker as a first-line therapy, an antihypertensive in the form of an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or calcium channel blocker, such as azelnidipine, should be used as a second-line drug to protect against vascular damage.

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Section: Bsupporting

confidence: 39%

Combination therapy based on the angiotensin receptor blocker olmesartan for vascular protection in spontaneously hypertensive rats

Tomita¹

2009

Mol Med Rep

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“…The relationship of LV concentricity with BP may have been partially concealed by the common use of RAS antagonists, the use of which was associated with a reduced rate of concentric LVH. RAS antagonists may attenuate myocardial remodeling in a partially BP-independent manner by antagonizing the effects of locally formed angiotensin II, resulting in reduced myocyte hypertrophy, fibroblast proliferation, matrix formation, and myocardial fibrosis (23)(24)(25). Volume status was the second most important parameter affecting the risk of LVH in dialyzed children.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Geometry in Children Receiving Chronic Peritoneal Dialysis

Bakkaloğlu

Borzych

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Left ventricular hypertrophy (LVH) is an independent risk factor and an intermediate end point of dialysis-associated cardiovascular comorbidity. We utilized a global pediatric registry to assess the prevalence, incidence, and predictors of LVH as well as its evolution in the longitudinal follow-up in dialyzed children.Design, setting, participants, & measurements Cross-sectional echocardiographic, clinical, and biochemical data were evaluated in 507 children on peritoneal dialysis (PD), and longitudinal data were evaluated in 128 patients. The 95 th percentile of LV mass index relative to height age was used to define LVH. ResultsThe overall LVH prevalence was 48.1%. In the prospective analysis, the incidence of LVH developing de novo in patients with normal baseline LV mass was 29%, and the incidence of regression from LVH to normal LV mass 40% per year on PD. Transformation to and regression from concentric LV geometry occurred in 36% and 28% of the patients, respectively. Hypertension, high body mass index, use of continuous ambulatory peritoneal dialysis, renal disease other than hypo/dysplasia, and hyperparathyroidism were identified as independent predictors of LVH. The use of renin-angiotensin system (RAS) antagonists and high total fluid output (sum of urine and ultrafiltration) were protective from concentric geometry. The risk of LVH at 1 year was increased by higher systolic BP standard deviation score and reduced in children with renal hypo/dysplasia.Conclusions Using height-adjusted left ventricular mass index reference data, LVH is highly prevalent but less common than previously diagnosed in children on PD. Renal hypo/dysplasia is protective from LVH, likely because of lower BP and polyuria. Hypertension, fluid overload, and hyperparathyroidism are modifiable determinants of LVH.

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“…Although the adrenergic receptor blockers are widely used to prevent cardiac hypertrophy (25,26), the underlying mechanisms of their effect remain to be elucidated. It has also been reported that sympathetic activation plays a critical role in the pressure-overload rat model of abdominal aortic constriction (27,28).…”

Section: Discussionmentioning

confidence: 99%

Adrenergic receptor blockade-induced regression of pressure-overload cardiac hypertrophy is associated with inhibition of the calcineurin/NFAT3/GATA4 pathway

Yang

Tan

et al. 2010

Mol Med Rep

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Abstract. calcineurin and its downstream effectors nuclear factor of activated T-cells 3 (nFaT3) and zinc finger-containing transcription factor (GATA4) have been implicated in the development of cardiac hypertrophy. The aims of the present study were to investigate alterations in the calcineurin/NFAT3/GATA4 pathway in pressure-overload hypertrophy, and to determine whether adrenergic receptor blockade affects this signaling pathway. In aorta-banded rats compared with sham-operated rats, a significant increase in the phosphorylation levels of calcineurin and GATA4 was observed (both p<0.05), while the NFAT3 phosphorylation level was markedly decreased (p<0.05). Oral administration of either the non-selective β blocker/α-1 blocker carvedilol or the selective β-1 blocker metoprolol, but not the selective α-1 blocker terazosin, significantly suppressed the activated calcineurin/NFAT3/GATA4 pathway (all p<0.05) in addition to inducing a regression of cardiac hypertrophy. Pressure overload-induced up-regulation of c-myc was markedly attenuated by treatment with either carvedilol or metoprolol (both p<0.05). The present findings may expand our understanding of the correlation between sympathetic activity and the calcineurin/NFAT3/GATA4 pathway, and highlight these signal transducers as effective targets in the management of pressure overload-induced cardiac hypertrophy.

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Different Effects on Inhibition of Cardiac Hypertrophy in Spontaneously Hypertensive Rats by Monotherapy and Combination Therapy of Adrenergic Receptor Antagonists and/or the Angiotensin II Type 1 Receptor Blocker under Comparable Blood Pressure Reduction

Cited by 19 publications

References 38 publications

Combination therapy based on the angiotensin receptor blocker olmesartan for vascular protection in spontaneously hypertensive rats

Combination therapy based on the angiotensin receptor blocker olmesartan for vascular protection in spontaneously hypertensive rats

Cardiac Geometry in Children Receiving Chronic Peritoneal Dialysis

Adrenergic receptor blockade-induced regression of pressure-overload cardiac hypertrophy is associated with inhibition of the calcineurin/NFAT3/GATA4 pathway

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