Effect of an Angiotensin II Type 1 Receptor Blocker, Valsartan, on Neurohumoral Factors in Patients with Hypertension: Comparison with a Long-Acting Calcium Channel Antagonist, Amlodipine

Ohbayashi, Yasunori; Tsutamoto, Takayoshi; Sakaguchi, Tomoko; Tanaka, Toshinari; Kanamori, Toshiyuki; Yokohama, Hiroshi; Sichiri, Gensyo; Hukai, Daisuke; Okabayashi, Tabito; Ozawa, Tomoya; Ishii, Chitose; Tsutsui, Takashi; Ohno, Keijin; Ohnishi, Masato; Wada, Atsuyuki

doi:10.1097/00005344-200312001-00016

Cited by 17 publications

(12 citation statements)

References 11 publications

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“…36 AngII is a crucial factor in the regulation of ALDO secretion, and previous studies have demonstrated that valsartan decreases the plasma ALDO concentration in hypertensive patients and in patients with heart failure. 37,38 Recently, it was reported that local ALDO is also important for cardiac hypertrophy and fibrosis in HCM. 39 Taken together, the findings suggest that valsartan may prevent not only upregulation of the rennin -angiotensin -aldosterone system via AngII suppression but also the breakthrough of ALDO.…”

Section: Discussionmentioning

confidence: 99%

Valsartan Decreases Type I Collagen Synthesis in Patients With Hypertrophic Cardiomyopathy

Kawano

Toda

Nakamizo

et al. 2005

Circ J

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Section: Discussionmentioning

confidence: 99%

Valsartan Decreases Type I Collagen Synthesis in Patients With Hypertrophic Cardiomyopathy

Kawano

Toda

Nakamizo

et al. 2005

Circ J

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“…In light of these findings, the development of compounds specially inhibiting P-gp function in cancer cells or BBB may contribute to the treatment of cancers and central nervous system diseases. Amlodipine, a calcium channel antagonist, belongs to dihydropyridines family and is currently applied in the treatment of hypertension [10] . A previous report has revealed that amlodipine has an inhibitory effect on P-gpmediated transport of dauxorubicin and digoxin [11] .…”

Section: Introductionmentioning

confidence: 99%

Modulation of P-glycoprotein function by amlodipine derivatives in brain microvessel endothelial cells of rats1

Liu

2005

Acta Pharmacologica Sinica

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Aim: To investigate whether the amlodipine derivatives, CJX1 and CJX2, have a modulative effect on P‐glycoprotein (P‐gp) function in rat brain microvessel endothelial cells (RBMEC). Methods: Isolated RBMEC were cultured in DMEM/F12 (1:1) medium. The amount of intracellular rhodamine (Rh123) was determined, using a fluorescence spectrophotometer, to evaluate the function of P‐gp. Results: The accumulation of Rh123 in RBMEC was potentiated in a concentration dependent manner after incubation with CJX1 and CJX2 at 1, 2.5, 5, and 10 μmol/L (P<0.01), but no accumulation of Rh123 was observed in human umbilical vein endothelial cells after incubation with CJX1 and CJX2 10 μmol/L (P>0.05). Accumulation of intracellular Rh123 was increased and efflux of intracellular Rh123 was decreased in a time‐dependent manner from 0–100 min after CJX1 and CXJ2 at 10 μmol/L treatment. The inhibitory effect of CJX1 and CJX2 on P‐gp function was reversible and remained even at 120 min after removal of CJX1 and CJX2 at 2.5 μmol/L from the medium. Conclusion: CJX1 and CJX2 exhibited a potent effect in the inhibition of P‐gp function in vitro.

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“…25 In this regard, the modest RAAS activation that can be encountered after DHPCA administration 54 can be also suppressed by ARBs. 55 Based on a recent meta-analysis 56 that stressed the role of fixed combinations in improving long-term adherence to therapy, as well as another study that highlighted the tendency of many hypertension physicians to use approaches that diverge from guideline recommendations, 57 the use of fixed combinations, in general, and of RAAS plus calcium channel blocking agents, in particular, seems to represent an extremely attractive tool in cardiovascular prevention in essential hypertensive patients. Finally, the combination of ARBs and DHPCAs is also likely to represent a more fruitful opportunity to obtain the more possible advantages from the suggested ancillary properties that might be responsible for the BP-independent benefits deriving from amlodipine and ARB monotherapies.…”

Section: Resultsmentioning

confidence: 99%

Role of combination therapy in the treatment of hypertension: Focus on valsartan plus amlodipine

2008

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Hypertension control is rare in clinical practice, particularly in high-risk patients. A large factor is therapeutic inertia deriving from poorly prescribed lifestyle changes, excess monotherapy use, and scarce on-treatment modifications. The use of drug combinations significantly improves blood pressure (BP) control; in particular, fixed combinations improve therapy without increasing daily pill intake, thereby favouring patient compliance and therapy continuation. The most widely used fixed combination is based on thiazide diuretics added to either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). Several large-scale clinical trials have been conducted showing that these combinations are effective in lowering BP. However, thiazide diuretics can reduce the metabolic benefits derived from renin-angiotensin-aldosterone system (RAAS) inhibitors in high metabolic risk patients. In contrast, ACE inhibitors or ARBs combined with dihydropyridine calcium channel antagonists (DHPCAs) exert a marked antihypertensive effect without decreasing metabolic protection by RAAS blockade. In the recent JIKEI heart study, approximately 60% of patients affected by hypertension, heart failure, coronary heart disease or their combination in the valsartan arm were simultaneously treated with DHPCAs. Of note, a 39% reduction in the primary endpoint of combined morbidity and mortality was reported in the valsartan compared with the non-valsartan arm. Furthermore, in a recent multinational study, 83% of 3161 hypertensive patients treated with valsartan and the DHCPA amlodipine reported a concontrolled BP after 8 weeks of treatment. As expected, amlodipine did not negatively influence the metabolic profile of patients, thereby supporting the role of ARB+DHPCA combinations as effective and promising tools in hypertension treatment. In summary, the combination of ARBs with DHPCAs is an effective strategy in hypertension treatment through synergy between their antihypertensive and vascular protective actions, persistent metabolic benefits deriving from RAAS inhibition, and reduced incidence of side effects.

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Effect of an Angiotensin II Type 1 Receptor Blocker, Valsartan, on Neurohumoral Factors in Patients with Hypertension: Comparison with a Long-Acting Calcium Channel Antagonist, Amlodipine

Cited by 17 publications

References 11 publications

Valsartan Decreases Type I Collagen Synthesis in Patients With Hypertrophic Cardiomyopathy

Valsartan Decreases Type I Collagen Synthesis in Patients With Hypertrophic Cardiomyopathy

Modulation of P-glycoprotein function by amlodipine derivatives in brain microvessel endothelial cells of rats1

Role of combination therapy in the treatment of hypertension: Focus on valsartan plus amlodipine

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