amlodipine Norvasc
Endothelin receptor antagonist combined with a calcium channel blocker attenuates renal injury in spontaneous hypertensive rats with diabetes.

Chen J, Gu Y, Lin F, Yang H, Zhu W, Ma J, Lin S.

Division of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, China.

OBJECTIVE: To investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long-acting calcium channel blocker, amlodipine, compared to the angiotensin-converting enzyme inhibitor, cilazapril, on the progressive renal injury in spontaneous hypertensive rats (SHR) with diabetes. METHODS: Diabetic hypertensive rats (SHR-DM) were induced by streptozotozin injected in male SHR (7-week-old),and divided into an untreated and three treated groups: 1) cilazapril treated group; 2) bosentan+amlodipine treated group; and 3) amlodipine treated group. Wistar Kyoto rats (WKY) and SHR rats served as normotensive and hypertensive control, respectively. The mean arterial blood pressure, renal function, endothelin and angiotensin II levels as well as the protein expression of renal extracellular matrix components and transforming growth factor (TGF)-beta1 were determined at the end of the 4th week. RESULTS: Mean arterial blood pressure significantly increased in SHR and SHR-DM rats compared to WKY rats. All the therapies reduced the blood pressure to normal levels. However, the enhanced urinary protein excretion, the decreased creatinine clearance as well as the increased plasma and intrarenal endothelin and angiotens in II levels were found in the untreated SHR-DM and prevented by treatment with bosentan+amlodipine and cilazapril. Similarly, these two kinds of therapies in SHR-DM abolished the overexpression of renal TGF-beta1 by Western blot analysis and reduced the accumulation of collagen type IV, laminin and fibronectin proteins by an immunochemical approach. Amlodipine monotherapy had no detectable effects on the above parameters. CONCLUSION: Bosentan combined with amlodipine can offer similar renoprotective effects on that of cilazapril and may be a potent therapy to attenuate renal injury by reducing renal protein levels of TGF-beta1 in diabetes with a hypertensive state.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12150723&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
[Health economic consequences of the use of irbesartan in patients in Germany with type 2 diabetes, nephropathy and hypertension]

[Article in German]

Palmer AJ, Annemans L, Roze S, Lamotte M, Rodby RA, Ritz E.

Center for Outcomes Research, Basel, Schweiz. AP thecenter.ch

BACKGROUND AND AIMS: The "Irbesartan in Diabetic Nephropathy Trial" (IDNT), demonstrated a reduction in the combined endpoint of doubling of serum creatinine, end-stage renal disease (ESRD) or death compared to control or amlodipine arms in patients with hypertension, type 2 diabetes and overt nephropathy when treated with irbesartan. Aim of this study is to compare long-term consequences in costs and outcomes of IDNT treatment alternatives from the German health care system's perspective. METHODS: A Markov model simulated progression from overt nephropathy to doubling of serum creatinine, end-stage renal disease, and death in patients with hypertension, type 2 diabetes and overt nephropathy for the three treatment arms. Treatment-specific probabilities were derived from IDNT. German-specific ESRD-related data were retrieved from published sources to reflect local management practices, ESRD outcomes and costs. A time horizon of 10 years was used. Delay in onset of ESRD and mean costs per patient were calculated. Future costs were discounted at 5 % per annum. RESULTS: The cumulative incidence of ESRD after 10 years with irbesartan (36 %) is lower compared to amlodipine (49 %) or control (45 %). Irbesartan leads to cost savings of 14 424 EUR and 8 720 EUR per patient versus amlodipine or control respectively. CONCLUSION: Treating patients with hypertension, type 2 diabetes and nephropathy using irbesartan lowers the cumulative incidence of ESRD and is cost-saving compared to amlodipine or control.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14703575&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Markov modeling analysis of health and economic outcomes of therapy with valsartan versus amlodipine in patients with type 2 diabetes and microalbuminuria.

Smith DG, Nguyen AB, Peak CN, Frech FH.

Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor 48109, USA. deans umich.edu

OBJECTIVE: To estimate 8-year health and economic outcomes of the angiotensin II receptor blocker valsartan versus the calcium channel blocker amlodipine in therapy of patients with type 2 diabetes and microalbuminuria based on clinical endpoints from a 6-month randomized controlled clinical trial, the MicroAlbuminuria Reduction With VALsartan (MARVAL) study. METHODS: We developed a Markov model that utilized urinary albumin excretion rate data to project patient distributions to 7 possible health states over 8 years. For each health state, we identified quality-adjustment weights (health utilities) and medical care costs from public sources. The model then calculated mean quality-adjusted survival, medical care costs, and cost-effectiveness ratios for each treatment arm. Treatment arms were compared with the incremental cost-effectiveness ratio. RESULTS: Patients treated with valsartan gained 7 months (mean) per patient of quality-adjusted survival relative to patients treated with amlodipine (77 versus 70 months; P<0.01); valsartan patients also incurred 32,412 dollars (mean) per patient lower medical costs than amlodipine patients (92,058 dollars versus 124,470 dollars; P<0.01). Model results were consistent for each year of analysis and robust to changes in key model parameters. CONCLUSION: This research (1) extends 6-month clinical trial outcomes to an 8-year period, (2) translates health outcomes from technical clinical endpoints to quality-adjusted survival, and (3) estimates economic consequences of therapeutic outcomes. The results quantify the favorable long-term health (i.e., quality-adjusted survival) and economic benefits (i.e., lower total medical costs) of therapy with valsartan, an angiotensin II receptor blocker, versus amlodipine, a calcium channel blocker, in the treatment of patients with type 2 diabetes and microalbuminuria based on an extension of the results of a short-term clinical (MARVAL) trial. These research findings are important to the extent patients with type 2 diabetes and microalbuminuria do not receive the recommended antihypertensive agents that block the renin-angiotensin system (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14720103&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Amlodipine: a cardiovascular drug with powerful antimicrobial property.

Kumar KA, Ganguly K, Mazumdar K, Dutta NK, Dastidar SG, Chakrabarty AN.

Division of Microbiology, Department of Pharmaceutical Technology, Jadavpur University, Calcutta 700 032, India.

Ten cardiovascular drugs were procured in pure form from their manufacturers in India and screened for antimicrobial property against fifteen known bacteria belonging to both gram-positive and gram-negative types. These bacteria were inhibited by the common antibiotics at 1-5 mg ml(-1) level through our earlier studies. Since most of the bacteria were moderate to highly responsive to amlodipine, this compound was further tested in vitro against 504 bacteria comprising 4 genera of gram-positive and 15 genera of gram-negative bacteria. Most of these were inhibited by the drug at 50-200 microg ml(-1) level and few strains were sensitive even at lower concentrations (10 microg ml(-1)). The bacteria could be arranged in the decreasing order of sensitivity towards amlodipine in the following manner: Staphylococcus aureus, Vibrio cholerae, Vibrio parahemolyticus, Shigella spp., Salmonella spp., Bacillus spp., whereas Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa were found to be resistant to the lower concentrations of the drug. Amlodipine was found to be bactericidal in nature when its mode of action was studied against S. aureus 6571, V. cholerae 14035 and Sh boydii 8 NCTC 254/66. The antibacterial activity of amlodipine could also be confirmed in vivo. When it was given to Swiss strain of white mice at different dosages (30 and 60 microg/mouse), it could significantly protect the animals challenged with 50 MLD of Salmonella typhimurium NCTC 74. According to Chi square test the in vivo data were highly significant (p<0.001).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14743981&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
The effect of amlodipine on exercise-induced pulmonary hypertension and right heart function in patients with chronic obstructive pulmonary disease.

Franz IW, Van Der Meyden J, Schaupp S, Tonnesmann U.

Klinik Wehrawald, BfA Schwarzenbacher Strasse 3 79682 Todtmoos, Germany. wehrawald-bfa t-online.de

The aim of the study was to investigate the pulmonary vasodilator effect of the dihydropyridine calcium channel blocker amlodipine in patients with clinically stable chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH). Many patients with COPD develop chronic PH and this may predict mortality in this disorder. The treatment with calcium channel blockers is accepted as a therapeutic strategy for primary pulmonary hypertension. In twenty male patients (mean age 57+/-7 years) with clinically stable COPD and PH, we investigated whether amlodipine could effectively decrease pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP) and improve right heart function. PAP was recorded by a balloon-tipped thermodilution catheter and cardiac output was determined in triplicate by thermodilution at rest and during exercise. In addition, blood gas values were determined from the capillary blood of the earlobe. All measurements were done under identical conditions before and after 18 days of chronic treatment: with 10 mg amlodipine once daily starting with 5mg in the first week. At a mean maximal achieved workload of 71.3+/-20 Watts, amlodipine achieved a significant reduction in PVR (-13.4%; p<0.01) and PAP (-12.1%; p<0.001) implying an improved right heart function assessed by a significant reduction in mean right atrial pressure (-20.6%; p<0.05). During the action of amlodipine there were no significant changes in pulmonary gas exchange and pulmonary capillary wedge pressure. Amlodipine given as a single daily oral dose of 10mg is a safe and effective pulmonary vasodilator in COPD patients with PH and leads to an improvement in right heart function.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12395224&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Synergism of atenolol and amlodipine on lowering and stabilizing blood pressure in spontaneously hypertensive rats.

Xu LP, Shen FM, Shu H, Miao CY, Jiang YY, Su DF.

Department of Pharmacology, Second Military Medical University, Shanghai, China.

This study was designed to investigate the possible synergism of atenolol and amlodipine on lowering and stabilizing blood pressure (BP) in spontaneously hypertensive rats. Sixty-four spontaneously hypertensive rats were randomly divided into eight groups. They were given 0.8% carboxymethylcellulose sodium (control), atenolol (10 mg/kg), amlodipine (0.5, 1 and 2 mg/kg) and the combinations of atenolol and amlodipine (10 + 0.5, 10 + 1 and 10 + 2 mg/kg), respectively. The drugs were given via a catheter of gastric fistula. BP was recorded for 25 h from 1 h before drug administration to 24 h after administration, in conscious, freely moving rats. It was found that combination of atenolol and amlodipine significantly decreased BP and systolic BP variability. From probability sum analysis it was found that the combination of atenolol and amlodipine, in a proportion as 10 : 1, was the best one (q = 1.54). In conclusion, the present work clearly demonstrated that there is a synergistic effect between atenolol and amlodipine in lowering and stabilizing the BP. The synergistic effect is highest when the dose proportion of the two drugs is 10 : 1.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14748751&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Inhibition of oxidative stress and improvement of endothelial function by amlodipine in angiotensin II-infused rats.

Zhou MS, Jaimes EA, Raij L.

Nephrology and Hypertension Section, Veterans Affairs Medical Center, 1201 NW 16th Street, Miami, FL 33125, USA.

BACKGROUND: Calcium channel blockers such as amlodipine are effective antihypertensive agents. In this study we investigated the effects of amlodipine on vascular oxidative stress, expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1), and endothelial function in angiotensin (Ang) II-infused rats. METHODS: Sprague-Dawley rats were treated with Ang II (0.7 mg/kg/day subcutaneously injected by mini-pump), with or without amlodipine (10 mg/kg/day by gavage), for 5 days and compared with control rats. Levels of aortic ring superoxide (O(2)(-)) and peroxynitrite (ONOO(-)) were determined, and systolic blood pressure (SBP) and endothelium-dependent relaxation were evaluated. RESULTS: Compared with control rats, Ang II-infused rats developed hypertension (175 +/- 3 v 135 +/- 2 mm Hg, P <.05), aortic hypertrophy (16.9 +/- 1.3 v 13.2 +/- 0.3 mg/cm, P <.05), left ventricular hypertrophy (0.236 +/- 0.003 v 0.204 +/- 0.004 g/100 g body weight, P <.05), and impaired endothelium-dependent relaxation (ED(50): 6.6 +/- 0.2 v 8.0 +/- 0.2 -log mol/L acetylcholine concentration, P <.05). Compared with control rats, Ang II-infused rats also had higher aortic levels of LOX-1 mRNA expression, O(2)(-)production (1005 +/- 140 v 608 +/- 159 counts/min/mg, P <.05), ONOO(-) production (1875 +/- 295 v 782 +/- 115 counts/min/mg, P <.05), and plasma free 8-F(2)alpha-isoprostanes (67.4 +/- 19.1 v 27.2 +/- 6.1 pg/mL, P <.05). In Ang II-infused rats SBP, aortic hypertrophy, endothelial dysfunction, LOX-1 expression, aortic O(2)(-) and ONOO(-) production, and plasma free 8-F(2)alpha-isoprostane levels were significantly reduced by amlodipine treatment. CONCLUSIONS: Amlodipine has antihypertensive and antioxidant activity in vivo, which effectively inhibits many of the oxidative stress-dependent mechanisms involved in Ang II-mediated cardiovascular injury.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14751660&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
[Alterations of antiproliferative effects of serum obtained from patients with acute cerebral infarction treated with a radical scavenger, edaravone, with or without amlodipine using an in vitro cultured basilar artery smooth muscle cells]

[Article in Japanese]

Yamaguchi T, Ida T, Kobayashi T, Hiraga M, Oishi K, Uchida MK, Echizen H.

Department of Hospital Pharmacy, Nakano General Hospital, 4-59-16 Chuou, Nakano-ku, Tokyo 164-8607, Japan.

The guinea-pig basilar artery smooth muscle cell (GBa-SM3) culture system in the Dulbecco's modified Eagle's medium for 3 days serves as a useful in vitro model for assessing antiproliferative effects of various therapeutic agents on vessels. With use of this system we studied whether human serum obtained from patients with acute cerebral infarction (n = 16) would have a proliferative effect on vessels and whether an administration of a free radical scavenger, edaravone, with or without amlodipine would elicit antiproliferative effects. The control serum was obtained from 3 healthy human subjects. Time courses of the cell growth and survival were measured colorimetrically by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrzolium bromide (MTT) test. The stimulatory effect on the proliferation of GBa-SM3 cells of patients' serum obtained immediately after infarction was significantly (p < 0.05) greater than those obtained from the same patients after the treatment of edaravone for 2 weeks. In addition, the serum obtained from the patients treated by edaravone and amlodipine (n = 7) showed a significantly (p < 0.05) greater antiproliferative effect than that obtained from those treated by edaravone (n = 9). In conclusion, edaravone may have a clinically beneficial antiproliferative effect on vascular smooth muscle cells. Co-administration of amlodipine, possessing an antioxidative calcium channel blocker, with edaravone may be a promising combination to patients with acute cerebral infarction. Further controlled clinical trials with a large number of patients should be warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14768352&dopt=Abstract amlodipine Norvasc