Comparative effects of chronic ACE inhibition and AT1 receptor blocked losartan on cardiac hypertrophy and renal function in hypertensive patients

Rosa, Maria Leonarda De; Cardace, Piercarmine; Rossi, Massimiliano; Baiano, A.; Cristofaro, A. De

doi:10.1038/sj.jhh.1001305

Cited by 41 publications

(34 citation statements)

References 17 publications

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“…In transgenic animal models, increased AT1R expression in the myocardium is sufficient to initiate hypertrophic growth (11,12). Furthermore, AT1R antagonist treatment prevents the development of cardiac hypertrophy in experimental animal models and in hypertensive patients (13).…”

Section: Rab1mentioning

confidence: 99%

Regulation of the Cell Surface Expression and Function of Angiotensin II Type 1 Receptor by Rab1-mediated Endoplasmic Reticulum-to-Golgi Transport in Cardiac Myocytes

Filipeanu¹,

Zhou²,

Claycomb

et al. 2004

Journal of Biological Chemistry

106

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Rab1GTPase coordinates vesicle-mediated protein transport specifically from the endoplasmic reticulum (ER) to the Golgi apparatus. We recently demonstrated that Rab1 is involved in the export of angiotensin II (Ang II) type 1 receptor (AT1R) to the cell surface in HEK293 cells and that transgenic mice overexpressing Rab1 in the myocardium develop cardiac hypertrophy. To expand these studies, we determined in this report whether the modification of Rab1-mediated ER-to-Golgi transport can alter the cell surface expression and function of endogenous AT1R and AT1R-mediated hypertrophic growth in primary cultures of neonatal rat ventricular myocytes. Adenovirus-mediated gene transfer of wild-type Rab1 (Rab1WT) significantly increased cell surface expression of endogenous AT1R in neonatal cardiomyocytes, whereas the dominant-negative mutant Rab1N124I had the opposite effect. Brefeldin A treatment blocked the Rab1WT-induced increase in AT1R cell surface expression. Fluorescence analysis of the subcellular localization of AT1R revealed that Rab1 regulated AT1R transport specifically from the ER to the Golgi in HL-1 cardiomyocytes. Consistent with their effects on AT1R export, Rab1WT and Rab1N124I differentially modified the AT1R-mediated activation of ERK1/2 and its upstream kinase MEK1. More importantly, adenovirus-mediated expression of Rab1N124I markedly attenuated the Ang II-stimulated hypertrophic growth as measured by protein synthesis, cell size, and sarcomeric organization in neonatal cardiomyocytes. In contrast, Rab1WT expression augmented the Ang II-mediated hypertrophic response. These data strongly indicate that AT1R function in cardiomyocytes can be modulated through manipulating AT1R traffic from the ER to the Golgi and provide the first evidence implicating the ERto-Golgi transport as a regulatory site for control of cardiomyocyte growth.

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Section: Rab1mentioning

confidence: 99%

Regulation of the Cell Surface Expression and Function of Angiotensin II Type 1 Receptor by Rab1-mediated Endoplasmic Reticulum-to-Golgi Transport in Cardiac Myocytes

Filipeanu¹,

Zhou²,

Claycomb

et al. 2004

Journal of Biological Chemistry

106

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“…27 ACE plays an important role in the physiology and pathophysiology of humans at high altitude 28 probably through its effects on skeletal muscle, 29 cardiac function, 30 sodium and fluid retention via the RAS, 31 and possibly on the respiratory center via the nucleus tractus solitarii as shown in a rat model. 32 ACE mRNA was highly expressed in pulmonary vessels of rats with high-altitude hypoxic pulmonary hypertension, 33 a sign indicating a failure in high altitude adaptation.…”

Section: Genotypic Distributions and Allelic Frequencies Of The Ace Imentioning

confidence: 99%

Adaptation to High Altitude in Sherpas: Association with the Insertion/Deletion Polymorphism in the Angiotensin-Converting Enzyme Gene

Droma

Hanaoka

Basnyat

et al. 2008

Wilderness & Environmental Medicine

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Objective-Sherpas are well known for their physical strength at high altitudes. They adapt to high altitude so well that little acute or chronic mountain sickness has been documented in them. The possible genetic basis for this adaptation is, however, unclear. The objective of this study was to elucidate the genetic background underlying this characteristic among Sherpas with respect to the angiotension-converting enzyme (ACE) gene. Conclusions-These findings suggest that the over-represented I allele of the ACE gene in Sherpas might be one of the fundamental genetic factors responsible for maintaining physiological low-altitude ACE activity at high altitude, which may have an advantageous physiological role in adapting to a high-altitude environment. Methods-We2

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“…14,22,25,27,28,41,69,78,79,84,88,89,92 Apart from one study in which there was a greater reduction of left ventricular hypertrophy with an ARB, 89 there were no differences between ACE inhibitor and ARB groups. Only one study evaluated a DRI; it found similar effects between aliskiren and an ARB.…”

Section: Left Ventricular Mass or Functionmentioning

confidence: 99%

“…Thirty studies (11 new, including two evaluating a DRI) presented original results on either serum creatinine/ GFR, 13,19,22,28,33,43,59,72,82,87,91,92 proteinuria, 11,29,58,60,80,103 or both. 23,30,46,49,56,62,65,73,81,97,99,102 The ten new studies that described changes in creatinine or glomerular filtration rate did not consistently demonstrate differential effects with use of ACE inhibitors versus ARBs, nor did the two studies comparing a DRI with the ACE inhibitor ramipril; 11,13 these findings were similar to those from the 2007 report.…”

Section: Serum Creatinine Level Glomerular Filtration Rate and Protmentioning

confidence: 99%

“…Forty-eight studies (18 new, including two evaluating a DRI) reported rates of one or more specific adverse events. 11,[13][14][15][16]19,24,[26][27][28][29][30]34,36,37,43,45,[47][48][49][50][51][52][53][54][55][57][58][59][61][62][63]65,68,72,74,75,78,81,87,89,90,94,95,97,[103][104][105] Given the large number of commonly reported specific adverse events, we focused on three specific events with the largest difference in absolute rates across studies: dizziness, headache, and cough.…”

Section: Serum Creatinine Level Glomerular Filtration Rate and Protmentioning

confidence: 99%

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Updated Report on Comparative Effectiveness of ACE inhibitors, ARBs, and Direct Renin Inhibitors for Patients with Essential Hypertension: Much More Data, Little New Information

et al. 2011

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OBJECTIVES:A 2007 systematic review compared angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in patients with hypertension. Direct renin inhibitors (DRIs) have since been introduced, and significant new research has been published. We sought to update and expand the 2007 review. DATA SOURCES: We searched MEDLINE and EMBASE (through December 2010) and selected other sources for relevant English-language trials. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We included studies that directly compared ACE inhibitors, ARBs, and/or DRIs in at least 20 total adults with essential hypertension; had at least 12 weeks of follow-up; and reported at least one outcome of interest. Ninety-seven (97) studies (36 new since 2007) directly comparing ACE inhibitors versus ARBs and three studies directly comparing DRIs to ACE inhibitor inhibitors or ARBs were included. STUDY APPRAISAL AND SYNTHESIS METHODS: A standard protocol was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality; and summarize the evidence. RESULTS: In spite of substantial new evidence, none of the conclusions from the 2007 review changed. The level of evidence remains high for equivalence between ACE inhibitors and ARBs for blood pressure lowering and use as single antihypertensive agents, as well as for superiority of ARBs for short-term adverse events (primarily cough). However, the new evidence was insufficient on long-term cardiovascular outcomes, quality of life, progression of renal disease, medication adherence or persistence, rates of angioedema, and differences in key patient subgroups. LIMITATIONS: Included studies were limited by followup duration, protocol heterogeneity, and infrequent reporting on patient subgroups. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS:Evidence does not support a meaningful difference between ACE inhibitors and ARBs for any outcome except medication side effects. Few, if any, of the questions that were not answered in the 2007 report have been addressed by the 36 new studies. Future research in this area should consider areas of uncertainty and be prioritized accordingly. CLINICAL CASEA 54-year-old woman with a history of hypertension is seen by her doctor for persistently elevated blood pressure in spite of adherence to hydrochlorothiazide 25 mg daily. She is overweight and has a strong family history of coronary artery disease. To control her blood pressure, she and her doctor discuss adding an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), or a direct renin inhibitor (DRI) to her regimen. She is primarily interested in avoiding the cardiovascular complications of hypertension, but does not want to take medication more than once a day, and she is concerned about side effects and the cost of her medication. What information is available to help guide her decision?Electronic supplementary material The online version of this article

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Comparative effects of chronic ACE inhibition and AT1 receptor blocked losartan on cardiac hypertrophy and renal function in hypertensive patients

Cited by 41 publications

References 17 publications

Regulation of the Cell Surface Expression and Function of Angiotensin II Type 1 Receptor by Rab1-mediated Endoplasmic Reticulum-to-Golgi Transport in Cardiac Myocytes

Regulation of the Cell Surface Expression and Function of Angiotensin II Type 1 Receptor by Rab1-mediated Endoplasmic Reticulum-to-Golgi Transport in Cardiac Myocytes

Adaptation to High Altitude in Sherpas: Association with the Insertion/Deletion Polymorphism in the Angiotensin-Converting Enzyme Gene

Updated Report on Comparative Effectiveness of ACE inhibitors, ARBs, and Direct Renin Inhibitors for Patients with Essential Hypertension: Much More Data, Little New Information

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