amlodipine Norvasc
[Contrast of losartan, fosinopril and amlodipine on cardiomyocyte apoptosis and left ventricular remolding in hypertensive rats]

[Article in Chinese]

Yu GL, Liang XQ, Zheng JQ.

Department of Geriatric Cardiology, Xiangya Hospital, Central South University, Changsha 410008, China.

OBJECTIVE: To investigate effects of losartan, fosinopril and amlodipine on cardiomyocyte apoptosis, cardiac remolding in the spontaneously hypertensive rats (SHR). METHODS: SHRs were treated with lorsartan (SHR-L), fosinopril (SHR-F), amlodipine (SHR-A), and untreated (SHR-C) respectively for 8 and 16 weeks. Cardiomyocyte apoptotic index (APOI), left ventricular mass, left ventricular mass index (LVM, LVMI), and plasma and myocardium angiotensin II(PAng II, MAng II) concentrations were examined. RESULTS: 1. The systolic blood pressure was decreased similarly in all treatment groups in 8 and 16 weeks. LVMIs were reduced significantly in all treatment groups. LVMI was significantly lower in SHR-F group than that in other two treatment groups in 16 weeks. 2. APOIs were decreased significantly in SHR-F group in 8 weeks and in all treatment groups, especially in SHR-F group in 16 weeks. 3. Compared with SHR-C group in both periods, PAng II and MAng II were significantly increased in SHR-L group, but MAng II concentration was only decreased significantly in SHR-F group in 8 weeks, and in SHR-F and SHR-A groups in 16 weeks. CONCLUSION: Losartan, amlodipine, and especially fosinopril can inhibit cardiomyocyte apoptosis, prevent myocardial fibrosis, and reverse heart hypertrophy. Inhibition of myocardium rennin--angiotension--aldsteron system may be the mechanism of the three drugs' cardioprotective effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12536482&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Effects of various antihypertensive drugs on the function of osteoblast.

Nishiya Y, Sugimoto S.

Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Machida, Japan.

Several studies have suggested that high blood pressure is associated with the risk of bone loss. Since various antihypertensive drugs are in wide use for the treatment of hypertension, it is important to investigate the influences of these drugs on bone metabolism. Osteoblasts play a pivotal role in the regulation of bone formation. During differentiation, they sequentially express type I collagen, alkaline phosphatase (ALP), other bone matrix proteins, and finally undergo mineral deposition. In this study, we examined the effects of various antihypertensive drugs on the function of osteoblast using clonal MC3T3-E1 cells. Drugs examined include dihydropyridine-type calcium channel blockers (benidipine, amlodipine, and nifedipine), angiotensin-converting enzyme (ACE) inhibitors (captopril, lisinopril, and enalapril), and angiotensin II receptor type1 (AT1) antagonists (TCV-116 and KW-3433). None of the ACE inhibitors or AT1 antagonists affected ALP activity or cellular DNA content significantly. In contrast, benidipine, amlodipine, and nifedipine increased ALP activity when used in amounts 1 pM, 100 nM, and 100 nM, respectively. Benidipine blocked calcium influx through the L-type voltage dependent calcium channel of MC3T3-E1 more potently than amlodipine or nifedipine. These calcium channel blockers did not change collagen accumulation. Benidipine significantly increased in vitro mineralization at a concentration of 1 nM and higher, while amlodipine did so at 1 microM and nifedipine did not. Comparison of the effective concentration of each calcium channel blocker in our study with the reported maximum serum concentration of each drug suggests that benidipine, but not amlodipine or nifedipine, promotes mineral deposition in human.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11411549&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
[Chiral separation of enantiomers of synthesized amlodipine and its intermediate by capillary electrophoresis]

[Article in Chinese]

Li BH, Yang GL, Wang DX, Zhang ZF, Chen Y.

College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.

A capillary electrophoretic method for the chiral separation of enantiomers of synthesized amlodipine and its intermediate was developed. Several cyclodextrins (CDs) were applied as the chiral selectors and it was found that the ionic modified carboxymethyl-beta-cyclodextrin (CM-beta-CD) could give satisfactory enantioselectivity. In addition, the effects of the pH value of the buffer system, the concentration of the CD and the voltage on the chiral separation were investigated. The optimized buffer for amlodipine and its intermediate enantiomers was a buffer containing 30 mmol/L phosphate and 50 mmol/L CM-beta-CD (pH 6.12). Under these conditions, the resolutions of enantiomers of amlodipine and its intermediate were 1.73 and 1.55, respectively.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12541917&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Chronic treatment with amlodipine modulates adrenocortical angiotensin II receptors in spontaneously hypertensive rats.

Kishida M, Otsuka F, Ogura T, Kataoka H, Nakamura Y, Yamauchi T, Takahashi M, Yokota K, Mimura Y, Makino H.

Department of Medicine III, Okayama University Medical School, Okayama University, Japan. endocrin cc.okayama-u.ac.jp

We investigated the effects of long-term treatment with calcium-antagonist, amlodipine, on angiotensin II receptors in the adrenal cortex of spontaneously hypertensive rats (SHR). Seven-week-old male SHR were treated with oral amlodipine (10 mg/kg/day) or vehicle (saline) for four weeks. Age-matched normotensive Wistar-Kyoto (WKY) rats were treated with the vehicle similar to control SHR. Systolic blood pressure (SBP) showed time-dependent increase in SHR but not in WKY rats, while amlodipine treatment significantly reduced the high SBP in SHR. Plasma renin activity was serially increased in SHR, which was further enhanced by amlodipine treatment. But the plasma aldosterone level which was increased in SHR was not changed by amlodipine. Competitive reverse transcriptase-polymerase chain reaction showed that the level of adrenocortical angiotensin II type 1 receptor (AT1R) mRNA progressively decreased in vehicle-treated SHR compared to WKY rats and that 4-week course of amlodipine treatment significantly increased AT1R mRNA in SHR to levels comparable to those in WKY rats. Amlodipine treatment reduced the level of adrenocortical angiotensin II type 2 receptor (AT2R) mRNA in SHR from 8 weeks of age. Thus, chronic amlodipine treatment differently modulates both adrenocortical AT1R and AT2R in SHR in a possibly direct manner.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11411801&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Comparison of amlodipine or nifedipine treatment with developing congestive heart failure: effects on myocyte contractility.

McElmurray JH, Mukherjee R, Patterson TM, Goldberg A, King MK, Hendrick JW, Gay DM, Clair MJ, Jolly JR, Spinale FG.

Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

BACKGROUND: Past studies have suggested that amlodipine, a dihydropyridine L-type Ca(2+) channel antagonist, may exert useful effects in congestive heart failure (CHF). The present study examined the effects of amlodipine or nifedipine treatment in a model of developing CHF on left ventricular (LV) pump function and myocyte contractility. Methods and Results: Pigs (25 kg) were randomly assigned to 1 of 4 groups: 1) pacing-induced CHF (rapid atrial pacing at 240 bpm) for 3 weeks (n = 9), 2) concomitant Ca(2+) channel blockade with amlodipine (1.5 mg/kg/day) and rapid pacing (n = 7), 3) concomitant Ca(2+) channel blockade with nifedipine (0.7 mg/kg twice daily) and rapid pacing (n = 7), and 4) sham controls (n = 7). LV fractional shortening fell with pacing CHF from baseline values (17% +/- 1% v 42% +/- 1%, P <.05). With rapid pacing and concomitant amlodipine treatment, LV fractional shortening increased from pacing CHF values (24% +/- 1%, P <.05) but was unchanged with concomitant nifedipine treatment (20% +/- 2%, P =.2). LV myocyte velocity of shortening, as measured by high speed videomicroscopy, was reduced with pacing CHF compared with controls (42 +/- 2 microm/s v 87 +/- 9 microm/s, P <.05), and increased from pacing CHF values with amlodipine or nifedipine treatment (62 +/- 8 microm/s, 64 +/- 4 microm/s, respectively; P <.05). Inotropic response to extracellular Ca(2+) (8 mmol/L) was reduced with pacing CHF (94 +/- 5 microm/s v 160 +/- 15 microm/s, P <.05) and increased from CHF values with amlodipine or nifedipine treatment (132 +/- 14 microm/s and 133 +/- 7 microm/s, respectively, P <.05) CONCLUSIONS: These results suggest that the primary mechanism for the effects of amlodipine on myocyte contractility in developing CHF is because of direct Ca(2+) channel blockade.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11420768&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice.

Murakami M, Nakagawasai O, Fujii S, Kameyama K, Murakami S, Hozumi S, Esashi A, Taniguchi R, Yanagisawa T, Tan-no K, Tadano T, Kitamura K, Kisara K.

Department of Molecular Pharmacology, Tohoku University School of Medicine, Sendai, Japan. mmura mail.cc.tohoku.ac.jp

We investigated the antinociceptive action of amlodipine, a dihydropyridine derivative, which acts on both L- and N-type voltage-dependent Ca2+ channels (VDCCs), in mice. Intrathecal injection of amlodipine (300 nmol/kg) significantly shortened the licking time in the late phase of a formalin test, while no effect was found with another dihydropyridine derivative, nicardipine (300 nmol/kg). Cilnidipine and omega-conotoxin GVIA also showed marked analgesic effects under the same experimental conditions. Transcripts of alpha1A, alpha1B, alpha1E, alpha1F, alpha1H, beta3, and beta4 subunits were detected by polymerase-chain reaction (PCR) in the dorsal root ganglion, suggesting the existence of a variety of voltage-dependent Ca2+ channels. Electrophysiological experiments showed that amlodipine and cilnidipine inhibit N-type currents in the dorsal root ganglion cells. These results suggest that amlodipine, cilnidipine, and omega-conotoxin GVIA exert their antinociceptive actions by blocking N-type Ca2+ channels in the primary nociceptive afferent fibers. Blocking of the Ca2+ channels results in attenuation of synaptic transmission of nociceptive neurons. Furthermore, it is suggested that some N-type Ca2+ channel blockers might have therapeutic potential as analgesics when applied directly into the subarachnoidal space.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11426839&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Antihypertensive efficacy of amlodipine in children with chronic kidney diseases.

von Vigier RO, Franscini LM, Bianda ND, Pfister R, Casaulta Aebischer C, Bianchetti MG.

Division of Nephrology, University Children's Hospital, Inselspital, CH-3010 Bern, Switzerland.

In adults the calcium antagonist amlodipine given once a day has proved to be an attractive addition to the antihypertensive armamentarium. The present report describes our experience in 43 paediatric outpatients (26 boys and 17 girls, aged between 1.1 and 19, median 9.8 years) with chronic kidney diseases. The patients were given amlodipine for 16 weeks as part of their antihypertensive treatment. Before amlodipine arterial pressure was 150 (142-163)/90 (84-95) mm Hg (median and interquartile range). Six patients withdrew from amlodipine because of oedema, flushing or headache. In the remaining patients amlodipine 7.7 (6.9-9.4) mg/m(2) body surface area once a day significantly decreased arterial pressure by 17 (13-22)/10 (7-13) mm Hg. The efficacy of amlodipine was more pronounced in girls than in boys. No changes in heart rate, body weight and circulating haemoglobin, sodium, potassium and creatinine were noted. In none of the patients circulating potassium, sodium or creatinine changed by more than 0.5 mmol/l, 5 mmol/l respectively 20%. In 11 patients concomitantly treated with cyclosporine the dosage and the trough-level of this agent were stable throughout the trial. In conclusion the present experience in paediatric outpatients with chronic kidney diseases supports the view that amlodipine is an effective and rather well tolerated antihypertensive drug when given once a day.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11439313&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Effect of calcium channel blockers on proteoglycan synthesis by vascular smooth muscle cells and low density lipoprotein--proteoglycan interaction.

Vijayagopal P, Subramaniam P.

Section of Cardiology, Department of Medicine, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, New Orleans, LA 70112, USA. pvijay lsuhsc.edu

Calcium channel blockers are known to retard atherosclerosis. In this study, we tested the hypothesis that one mechanism by which calcium channel blockers retard atherosclerosis is through the modulation of proteoglycan metabolism by vascular smooth muscle cells. We investigated the effect of amlodipine and nifedipine on proteoglycan synthesis by human aortic smooth muscle cells and the ability of the newly synthesized proteoglycans to bind low density lipoprotein (LDL). Confluent smooth muscle cells were incubated with [(35)S]sulfate alone or [(35)S]sulfate and [(3)H]leucine in the presence and absence of different concentrations of amlodipine and nifedipine (0.1--20 microg/ml) for 24 h, and newly synthesized proteoglycans were analyzed. Both amlodipine and nifedipine inhibited proteoglycan synthesis by smooth muscle cells in a dose-dependent manner; however, amlodipine was significantly more potent than nifedipine in this regard. In the presence of 20 microg/ml amlodipine, media and cellular proteoglycans decreased by 56%. This was due to inhibition of de novo proteoglycan synthesis by amlodipine. Compared with the proteoglycans synthesized by control smooth muscle cells, those synthesized by cells exposed to amlodipine were smaller and less sulfated, and contained fewer glycosaminoglycan chains. In addition, proteoglycans synthesized by cells treated with amlodipine bound LDL with low affinity. These results suggest that amlodipine may protect against atherosclerosis through a proteoglycan-mediated mechanism.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11472734&dopt=Abstract amlodipine Norvasc