amlodipine Norvasc
[Effect of calcium antagonists verapamil and amlodipine on the risk of development of atrial fibrillation after coronary artery bypass grafting]

[Article in Russian]

Popov SV, Kandinskii ML, Kozlov BN, Antonchenko IV, Evtushenko AV, Dzhavadova GK, Vecherskii IuIu, Akhmedov ShD, Afanas'ev SA, Shipulin VM.

NII kardiologii Tomskogo nauchnogo tsentra Sibirskogo otdeleniia RAMN, Tomsk.

AIM: To assess effect of calcium antagonists amlodipine and verapamil on the risk of development of atrial fibrillation after coronary artery bypass surgery. MATERIAL: Of 74 patients subjected to mammary artery and venous coronary bypass grafting with the use of cardiopulmonary bypass 19 received amlodipine and 21 - verapamil. RESULTS AND CONCLUSION: Attacks of atrial fibrillation during 24 hour ECG monitoring were registered in 22.9% of patients mostly on days 2 and 3 after surgery. In verapamil treated patients atrial fibrillation occurred 1.5-2 times more often than in amlodipine treated patients or in patients receiving no calcium antagonists. This could possibly be explained by pronounced slowing of atrio-ventricular conduction by verapamil at the background of postoperative general "irritation" of the atrial myocardium.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12891296&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Amlodipine modulates THP-1 cell adhesion to vascular endothelium via inhibition of protein kinase C signal transduction.

Yu T, Morita I, Shimokado K, Iwai T, Yoshida M.

Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

Inflammatory responses play an important role in atherosclerosis. To critically assess the effect of dihydropyridines in inflammatory reactions, we conducted a monocyte-endothelial adhesion assay with monocytic THP-1 cells treated with amlodipine under flow conditions in vitro. THP-1 cells were incubated in the presence of amlodipine (10 micromol/L) for 48 hours and then perfused over activated (interleukin-1beta, 10 U/mL, 4 hours) human umbilical vein endothelial cells. The adhesion of THP-1 cells was significantly reduced after amlodipine treatment (P<0.001); however, flow cytometric analysis reveled that the expression levels of integrins in THP-1 cells were not significantly altered. Furthermore, Western blotting analysis of THP-1 cell lysates revealed that translocation of RhoA from the cytosol to the membrane was significantly diminished after amlodipine treatment. In addition, activation of protein kinase C-alpha and -beta, as well as intracellular calcium influx, induced by phorbol 12-myristate 13-acetate, was diminished after amlodipine treatment. Pretreatment of THP-1 cells with calphostin C, a potent inhibitor of protein kinase C, significantly reduced THP-1 adhesion to vascular endothelium, whereas activation of beta1-integrin was reduced after amlodipine treatment in THP-1 cells, based on the immunoreactivity of an activation-specific antibody for beta1-integrin. Similar inhibitory effects were observed when we used freshly isolated peripheral blood mononuclear cells. These findings suggest a potential role for amlodipine in monocyte-endothelial interactions by modulation of protein kinase C- and RhoA-dependent mechanisms, which might account for its vascular protective effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12900427&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
A comparative analysis of amlodipine and felodipine in a military outpatient population: efficacy, outcomes, and cost considerations.

Blivin SJ, Pippins J, Annis LG, Lyons F.

Department of Primary Care, Naval Medical Clinic, Quantico, VA, USA. blivin dellnet.com

BACKGROUND: This retrospective study compared the efficacy, tolerability, and cost of two dihydropyridine calcium channel blockers. METHODS: Charts of patients who had been on continuous antihypertensive therapy with amlodipine or felodipine for at least 6 months were reviewed. Analyses include mean changes in blood pressure, percentage of patients achieving blood pressure (BP) < 140/90 mm Hg, average dose, and cost per day of the two calcium channel blockers, average cost of additional medication, total medication cost per day, and cost to achieve BP control. RESULTS: Eighty-seven percent of amlodipine-treated patients achieved BP control compared with 33% of felodipine-treated patients. Total medication cost to achieve BP control was 0.87 dollars per day for patients on amlodipine compared with 1.79 dollars per day for patients on felodipine. CONCLUSIONS: Amlodipine produced BP control in a greater percentage of patients than did felodipine at a lower total cost to achieve BP control. When evaluating the total cost of antihypertensive treatment, the cost of a drug alone can be misleading.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12901461&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Angiotensin inhibition reduces glomerular damage and renal chemokine expression in MRL/lpr mice.

Perez De Lema G, De Wit C, Cohen CD, Nieto E, Molina A, Banas B, Luckow B, Vicente AB, Mampaso F, Schlondorff D.

Medizinische Poliklinik der Ludwig-Maximilians-Universitat, Munchen, Germany.

Beneficial effects of angiotensin II inhibition during inflammatory renal disease may involve both hemodynamic and nonhemodynamic mechanisms. To analyze whether angiotensin II inhibition has protective effects on lupus-like, autoimmune-mediated renal damage in MRL/lpr mice, four groups of mice were treated orally for 6 weeks with: 1) vehicle, 2) enalapril (3.0 mg/kg per day), 3) candesartan cilexetil (5.0 mg/kg), or 4) amlodipine (10 mg/kg) as a blood pressure control (n = 9-12/group). All antihypertensive treatments lowered blood pressure to a similar level compared with vehicle group (enalapril: 99.8 +/- 8.3 mm Hg; candesartan: 101 +/- 9 mm Hg; amlodipine: 103.8 +/- 6.7 mm Hg; vehicle: 113.5 +/- 4.6 mm Hg). Vehicle-treated mice developed a moderate glomerular injury with albuminuria (35.1 +/- 39.0 microg/mg of creatinine). Glomerular lesions consisted of immune complex deposition and mesangial expansion with increased mesangial cell proliferation. Amlodipine treatment had no significant protective effects. In contrast to vehicle- and amlodipine-treated mice, those subjected to angiotensin II blockade with enalapril or candesartan had reduced albuminuria, glomerular expansion, and mesangial proliferation. This was associated with significantly reduced renal chemokine mRNA expression compared with vehicle treatment. Our results show that inhibition of angiotensin II has protective effects on the glomerular damage of MRL/lpr mice that extend beyond hemodynamics and involve down-modulation of glomerular inflammation, reduction of mesangial cell proliferation, and decrease in chemokine expression.

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amlodipine Norvasc
Synergistic effect of nicorandil and amlodipine on lysosomal hydrolases during experimental myocardial infarction in rats.

Sathish V, Ebenezar KK, Devaki T.

Department of Biochemistry and Molecular Biology, University of Madras, Guindy Campus, Chennai 600 025, India.

The synergistic effect of nicorandil (K(ATP) channel opener) and amlodipine (calcium channel blocker) on lysosomal hydrolases in serum and heart was examined by determining the activity of beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase, cathepsin-D and acid phosphatase on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for 2 d showed significant increase in serum and heart lysosomal hydrolases activity. Isoproterenol administration to rats resulted in decreased stability of the membranes, which was reflected by the lowered activity of cathepsin-D and beta-glucuronidase in mitochondrial, nuclear, lysosomal and microsomal fractions. Pretreatment with nicorandil (2.5 mg kg(-1) daily, p.o.) and amlodipine (5.0 mg kg(-1) daily, p.o.) for 3 d significantly prevented these alterations and restored the enzyme activity to near normal. These findings demonstrate that the pretreatment with nicorandil and amlodipine could preserve lysosomal integrity and hence establish the cardioprotective effect of the combination.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14499179&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Biochemical changes on the cardioprotective effect of nicorandil and amlodipine during experimental myocardial infarction in rats.

Sathish V, Ebenezar KK, Devaki T.

Department of Biochemistry and Molecular Biology, Guindy Campus, University of Madras, Chennai 600025, India.

The synergistic protective effect of nicorandil (KATP channel opener) and amlodipine (calcium channel blocker) on mitochondrial respiration and mitochondrial lipid contents were examined on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for 2 days showed significant changes in mitochondrial respiration and mitochondrial lipid profile levels. Pretreatment with nicorandil (2.5 mg kg(-1) daily, p.o.) and amlodipine (5.0 mg kg(-1) daily, p.o.) for 3 days significantly prevented these alterations and restored the mitochondrial respiration and mitochondrial lipid contents to near normal. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the synergistic protective effect of nicorandil and amlodipine on mitochondrial respiration and its membrane integrity during isoproterenol-induced cardiac damage.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14527820&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Amlodipine activates the endothelial nitric oxide synthase by altering phosphorylation on Ser1177 and Thr495.

Lenasi H, Kohlstedt K, Fichtlscherer B, Mulsch A, Busse R, Fleming I.

Institut fur Kardiovaskulare Physiologie, Klinikum der JWG-Universitat, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.

OBJECTIVE: The Ca2+ antagonist amlodipine increases the generation of nitric oxide (NO) from native and cultured endothelial cells. The aim of this investigation was to determine whether or not the activation of the endothelial NO synthase (eNOS) by this Ca2+ antagonist is related to alterations in eNOS phosphorylation. METHODS AND RESULTS: In isolated, pre-contracted, endothelium-intact porcine coronary arteries, amlodipine elicited an NO-mediated relaxation and a leftward shift in the concentration-relaxation curve to bradykinin. Moreover, the Ca2+ antagonist increased the generation of NO from native endothelial cells, as detected by electron spin resonance spectroscopy and stimulated an 8-fold increase in cyclic GMP levels in cultured endothelial cells. In unstimulated endothelial cells, eNOS was not phosphorylated on Ser1177 but was phosphorylated on Thr495. Amlodipine elicited the phosphorylation of Ser1177 and attenuated Thr495 phosphorylation, with a time course similar to that of eNOS activation. The amlodipine-induced relaxation of porcine coronary arteries was attenuated by the B2 kinin receptor antagonist, icatibant, but this antagonist did not affect amlodipine-induced changes in eNOS phosphorylation in cultured endothelial cells. Moreover, amlodipine elicited the NO-mediated relaxation of rat aortic rings which do not express the B2 receptor. Amlodipine time-dependently attenuated the phosphorylation of protein kinase C (PKC) in endothelial cells, with a time course similar to the changes in eNOS phosphorylation, and prevented the phorbol-12-myristate-13-acetate-induced activation of PKC. The PKC inhibitor, Ro 31-8220, also elicited the phosphorylation of Ser1177 and the dephosphorylation of Thr495 in cultured cells and induced a leftward shift in the concentration-relaxation curve to bradykinin in rings of porcine coronary artery. CONCLUSION: The Ca2+ antagonist, amlodipine, enhances endothelial NO generation by inducing changes in the phosphorylation of eNOS. Although the activation of eNOS was related to the activation of the B2 kinin receptor in the porcine coronary artery, a B2 receptor-independent mechanism involving the inhibition of PKC appears to account for the effects observed in the rat aorta as well as in cultured endothelial cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14553824&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Renoprotective effects of benidipine in combination with angiotensin II type 1 receptor blocker in hypertensive Dahl rats.

Yao K, Sato H, Ina Y, Suzuki K, Ohno T, Shirakura S.

Biomedical Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan. kozo.yao kyowa.co.jp

We examined the effects of the angiotensin II type 1 receptor blocker candesartan, the calcium channel blockers benidipine and amlodipine, hydralazine, and the combination of candesartan and benidipine or amlodipine on blood pressure and renal function in Dahl salt-sensitive (DS) hypertensive rats. Male DS rats (5 weeks of age) were fed a high-salt (8% NaCl) diet, resulting in hypertension accompanied by glomerular sclerosis and an increased urinary albumin excretion. Drugs were orally administered from 2 to 6 weeks after the start of the feeding. Although candesartan (1 or 10 mg/kg) had little effect on the blood pressure, benidipine (4 mg/kg), amlodipine (4 mg/kg) and hydralazine (5 mg/kg) had similar hypotensive effects. Benidipine, but not amlodipine, hydralazine, or candesartan, significantly inhibited the increase in the albuminuria and glomerular sclerosis. The combination of candesartan (1 mg/kg) and benidipine (4 mg/kg) lowered the levels of blood pressure and albuminuria more effectively than the combination of candesartan (1 mg/kg) and amlodipine (4 mg/kg). These results indicate that benidipine is effective in preventing the impairment of renal function in DS hypertensive rats, and suggest that additional benefits can be expected by combination therapy with benidipine and an angiotensin II type 1 receptor blocker.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14567503&dopt=Abstract amlodipine Norvasc