amlodipine Norvasc
Comparative study of the antihypertensive activity of Marrubium vulgare and of the dihydropyridine calcium antagonist amlodipine in spontaneously hypertensive rat.

Bardai SE, Lyoussi B, Wibo M, Morel N.

UFR Physiologie-Pharmacologie, Faculte des Sciences Dahar-Elmahraz, Fes, Morocco.

Water extract of Marrubium vulgare is widely used as antihypertensive treatment in folk medicine. We have compared the effect of 10-week-long treatment with amlodipine or Marrubium water extract on systolic blood pressure (SBP), cardiovascular remodeling and vascular relaxation in spontaneously hypertensive rats (SHR). Both treatments produced similar decrease in SBP. Amlodipine treatment reduced left ventricle, aortic and mesenteric artery weight. Marrubium treatment had a significant antihypertrophic effect in aorta only. Relaxation to acetylcholine (ACh) of mesenteric artery was improved by Marrubium but not by amlodipine treatment. These results demonstrate that, in addition to its antihypertensive effect, Marrubium water extract improved the impaired endothelial function in SHR.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15554450&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Effect of amlodipine on insulin resistance & tumor necrosis factor-alpha levels in hypertensive obese type 2 diabetic patients.

Ersoy C, Imamoglu S, Budak F, Tuncel E, Erturk E, Oral B.

Department of Endocrinology & Metabolism, Uludag University Medical School, Bursa, Turkey. ecanan uludag.edu.tr

BACKGROUND & OBJECTIVES: Tumour necrosis factor-alpha (TNF-alpha) has been suggested to play a key role in insulin resistance (IR) in obesity and may contribute to the development of type 2 diabetes mellitus. Recently, studies are focused on the effect of antihypertensive drugs on insulin sensitivity and cytokines. We undertook this study to evaluate the effect of amlodipine, a long-acting dihydropyridine calcium channel blocker treatment on TNF-alpha, homeostasis model assessment (HOMA) IR and leptin levels in obese hypertensive type 2 diabetic patients. METHODS: Amlodipine 5-10 mg for 12 wk was given to type 2 diabetic patients in the amlodipine group. Pre- and post-treatment values of laboratory parameters in the amlodipine group were compared with those of normotensive nondiabetic obese controls. At baseline blood pressures (BP) and metabolic parameters were measured in all patients and repeated after 12 wk in the amlodipine group. RESULTS: Basal waist-to-hip ratio, systolic and diastolic BPs, fasting glucose, TNF-alpha and HOMAIR values of the amlodipine group were higher than the control group. No difference was detected in body mass index, fasting insulin, hemoglobin A1c and leptin values between groups. The systolic and diastolic BPs, fasting glucose, HOMA-IR and TNF-alpha values decreased significantly after the treatment. But, there was no correlation between percentage change in TNF-alpha and HOMA-IR. INTERPRETATION & CONCLUSION: Besides reducing BP, amlodipine seemed to improve IR and decrease TNF-alpha levels. In this context, these properties may provide additional benefits of antihypertensive drug regimens chosen for this population, but larger group interventions are needed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15591634&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Different effect of losartan and amlodipine on penile structures in male spontaneously hypertensive rats.

Toblli JE, Stella I, Mazza ON, Ferder L, Inserra F.

Laboratory of Experimental Medicine, Hospital Aleman, Buenos Aires, Argentina. jtoblli hospitaleman.com

BACKGROUND: Erectile dysfunction is highly prevalent in hypertensive patients. Since both angiotensin II receptor type-1 blockers (ARBs) and calcium antagonists are current and effective antihypertensive drugs, the aim of this study was to determine possible differences between ARBs and calcium antagonists concerning the protection of penile structures from the deleterious effects of arterial hypertension. METHODS AND RESULTS: During 6 months, 3 groups of male spontaneously hypertensive rats (SHR) and 1 of Wistar-Kyoto (WKY) rats, as a control group, were studied: SHR without treatment; SHR with losartan (L) 30 mg/kg/day; SHR with amlodipine (A) 3 mg/kg/day, and WKY without treatment. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries, cavernous tissue fibrosis and collagen type III (COL III) were evaluated. After 6 months, SHR+L and SHR+A showed a similar reduction in blood pressure compared with untreated SHR. However, only SHR+L and control WKY presented significantly lower values of: CSM (p < 0.01), VSM (p < 0.01), and COL III (p < 0.01) when compared with either untreated SHR or SHR+A. There was also a positive correlation between left ventricular mass and proteinuria with VSM from cavernous arteries, CSM and COL III in untreated SHR and SHR+A. These relations were not present in SHR+L and WKY. CONCLUSION: Although losartan and amlodipine achieved similar blood pressure control, losartan but not amlodipine showed a significant protective role against structural changes in the vessels and cavernous spaces of the erectile tissue caused by arterial hypertension. Copyright 2004 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15591797&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
[Enantioseparation of amlodipine maleate by capillary electrophoresis using colominic acid as a chiral selector and the mechanism of chiral recognition]

[Article in Chinese]

Du YX, Chen JM, Zheng ZH.

Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, China. dyingxiang hotmail.com

AIM: Colominic acid, a novel chiral selector, was applied to enantioseparation of dihydropyridine derivative by capillary electrophoresis. A new method was developed for enantioseparation of amlodipine maleate, a novel calcium channel blocking therapeutic agent. The chiral recognition mechanism of colominic acid to amlodipine maleate was studied. METHODS: Capillary electrophoresis was performed, and the effects of separation conditions on chiral separation were examined, including concentration of chiral selector, buffer pH, capillary temperature, applied voltage and molecular mass of colominic acid. RESULTS: The optimum conditions were additive concentration of 8.0%, buffer pH at 3.00, capillary temperature at 15 degrees C, 12 kV for applied voltage and 3 x 10(4) for molecular mass of colominic acid. Under optimum conditions complete separation was achieved between the enantiomers of amlodipine maleate with resolution as high as 2.20. CONCLUSION: The cliral separation was based on the multipoint recognition between colominic acid and amlodipine maleate. It is recommended that this simple, rapid and selective method be used for enantioseparation of amlodipine maleate. As far as polysaccharides were concerned, colominic acid was first used for enantioseparation of amlodipine maleate.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15606025&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Calcium channel blocker versus angiotensin II receptor blocker in autosomal dominant polycystic kidney disease.

Nutahara K, Higashihara E, Horie S, Kamura K, Tsuchiya K, Mochizuki T, Hosoya T, Nakayama T, Yamamoto N, Higaki Y, Shimizu T.

Department of Urology, Kyorin University School of Medicine, Tokyo, Japan. kinuta kyorin-u.ac.jp <kinuta kyorin-u.ac.jp>

BACKGROUND: Although hypertension is commonly found in patients with autosomal dominant polycystic kidney disease (ADPKD), there is no consensus about which antihypertensive agents are most appropriate. The effects of calcium channel blockers (CCB) and angiotensin II receptor blockers (ARB) on blood pressure and renoprotection were compared in hypertensive patients with ADPKD. METHODS: We randomly assigned 49 participants to CCB amlodipine-based (2.5-10 mg/day) or ARB candesartan-based (2-8 mg/day) regimens. Twenty-five patients (13 males and 12 females) received amlodipine, and 24 patients (13 males and 11 females) received candesartan. This was followed up for 36 months. RESULTS: Baseline characteristics were similar, and blood pressure was well controlled in both groups throughout the study period. Six out of 25 (24.0%) amlodipine and 1 out of 24 (4.2%) candesartan patients were terminated from the protocol due to a twofold increase in serum creatinine and/or decrease in creatinine clearance (Ccr) to half of the baseline. The renal event-free survival rate was significant (p < 0.05, Breslow-Gehan-Wilcoxon test). Serum creatinine was higher in the amlodipine group than in the candesartan group at 24 and 36 months (p < 0.05). The decrease in Ccr at 36 months was larger in the amlodipine group than in the candesartan group (DeltaCcr: -20.9 +/- 13.1 vs. -4.8 +/- 13.8 ml/min, p < 0.01). Urinary protein excretion was significantly lower in the candesartan group than in the amlodipine group at 36 months. Urinary albumin excretion was significantly lower in the candesartan group than in the amlodipine group at 12, 24 and 36 months. CONCLUSIONS: The renoprotective effect of candesartan is considered more favorable than amlodipine in the treatment of ADPKD. This is independent of the antihypertensive effect per se. Copyright (c) 2005 S. Karger AG, Basel.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15637459&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Effect of antihypertensive treatment with candesartan or amlodipine on glutathione and its redox status, homocysteine and vitamin concentrations in patients with essential hypertension.

Muda P, Kampus P, Zilmer M, Ristimae T, Fischer K, Zilmer K, Kairane C, Teesalu R.

Department of Cardiology, University of Tartu, Tartu, Estonia. Piibe.Muda kliinikum.ee

OBJECTIVE: To compare the effect of candesartan or amlodipine on concentrations of cellular markers of oxidative stress, plasma homocysteine and vitamins in hypertensive patients. METHODS: Forty-nine middle-aged patients with untreated stage I-II essential hypertension were recruited in a randomized double-blind double-dummy study to receive a daily dose either of 8 mg candesartan (n = 25) or 5 mg amlodipine (n = 24) for 16 weeks. Blood pressure, reduced glutathione (GSH) and oxidized glutathione (GSSG), glutathione redox ratio (GSSG : GSH) in red blood cells, plasma homocysteine, vitamin B12 and folic acid status were measured at baseline, at week 2 and at week 16. The same parameters were measured in 32 healthy age- and sex-matched controls. An increase in homocysteine of at least 2 micromol/l was considered significant. RESULTS: Hypertensive patients had significantly greater oxidative stress and homocysteine concentrations than controls. In addition to a significant decrease in blood pressure, in both treatment groups GSSG decreased (P < 0.03), GSSG : GSH had a tendency to decrease (P = 0.054), but homocysteine did not change. An increase in homocysteine concentration of at least 2 micromol/l was found in 12 patients (five in the candesartan group, seven in the amlodipine group), with a significant decrease in folic acid concentration and no changes in cellular oxidative stress. In patients with no increase in homocysteine concentration, both GSSG (P < 0.02) and GSSG : GSH (P = 0.051) decreased. GSH and vitamin B12 did not change in any of the groups studied. CONCLUSION: Untreated hypertension is associated with disturbed glutathione redox status and increased plasma homocysteine concentrations. Both candesartan and amlodipine had favourable effects on cellular oxidative stress, but the oxidative stress status did not decrease in patients with adverse changes in homocysteine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15643131&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Amlodipine ameliorates myocardial hypertrophy by inhibiting EGFR phosphorylation.

Liao Y, Asakura M, Takashima S, Kato H, Asano Y, Shintani Y, Minamino T, Tomoike H, Hori M, Kitakaze M.

Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0781, Japan.

The effects of long-acting calcium channel blockers on pressure overload-induced cardiac hypertrophy have been little studied in experimental animals and the underlying mechanisms are not fully understood. We previously reported that cardiomyocyte hypertrophy could be induced via phosphorylation of the epidermal growth factor receptor (EGFR). In this study, we investigated whether amlodipine attenuates cardiac hypertrophy by inhibiting EGFR phosphorylation. We found that amlodipine dose-dependently inhibited epinephrine-induced protein synthesis and EGFR phosphorylation in cultured neonatal rat cardiomyocytes. Our in vivo study revealed that amlodipine could ameliorate myocardial hypertrophy induced by transverse aortic constriction (TAC) in C57/B6 mice. One week after TAC, amlodipine treatment (3 mg/kg/day) significantly reduced the heart-to-body weight ratio (6.04 +/- 0.16 mg/g vs. 6.90 +/- 0.45 mg/g in untreated TAC mice, P < 0.01). These results indicate that amlodipine ameliorates cardiomyocyte hypertrophy via inhibition of EGFR phosphorylation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15652507&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
[Safety and antihypertensive efficacy of the dihydropyridine calcium antagonist Amlodipine besylate--results from an observational study in 9,672 patients]

[Article in German]

Keck M, Sauerbrey-Wullkopf N, Regourd E, Clemens A.

Fachklinik fur Herz- und Kreislaufkrankheiten, Drei-Burgen-Klinik, Bad Munster am Stein. michael.keck lva-rheinland-pfalz.de

OBJECTIVES: This observational study investigated prescription behavior and the efficacy and safety of Amlodipine besylate in hypertensive patients. METHODS: 9,672 hypertensive patients were treated with Amlodipine besylate 5-10 mg/day for 12 weeks. At the end of the observation period, the participating physicians were asked to give their subjective evaluation of the efficacy and safety of treatment with Amlodipine besylate as well as their therapeutic considerations regarding the use of Amlodipine besylate. RESULTS: 55.2% of the patients received Amlodipine besylate in combination with other antihypertensive agents. The mean baseline blood pressure was 168.0/96.7 mmHg and the mean blood pressure reduction achieved at the end of the observation period was -28.5/-14.5 mmHg. In 80.3% of the total population, a reduction to diastolic blood pressure values of < 90 mmHg was achieved. A reduction to systolic blood pressure values of < 140 mmHg was obtained in 41.6% of the patients. Adverse events were reported by only 1.2% of the patients. For the vast majority of the patients, efficacy (96.6%) and safety (98.9%) were rated "very good" or "good" by their physicians. 24-hour efficacy with once daily dosing was given as the most important argument for using Amlodipine besylate. CONCLUSION: The observation study confirmsthat Amlodipine besylate is an effective and safe antihypertensive drug both in mono and combination therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15662901&dopt=Abstract amlodipine Norvasc