Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new adalat research articles will be listed here shortly after becoming available to us.
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Medical research on adalat
J Pharmacol Exp Ther. 2008 Aug 21;
Hernandez JM, Cox G, Janssen LJ
The airway response to deep inspirations (DIs) in asthmatics has been shown to be ineffective in producing bronchodilation, and can even cause bronchoconstriction. However, the manner by which a DI is able to cause bronchoconstriction remains ambiguous. We sought to investigate the pathway involved in this stretch-activated contraction, as well as whether this contraction is intrinsic to airway smooth muscle (ASM). Briefly, intact bovine bronchial segments were dissected and side branches ligated, then mounted horizontally in an organ bath. Intraluminal pressure was measured under isovolumic conditions. Instantaneously opening and then closing the tap on a column of fluid 5-30 cm high evoked a sudden increase in intraluminal pressure (equivalent to the height of the column of fluid) followed by a stress relaxation response of the ASM. When tissues were stimulated with carbachol (10(-8)M) or serotonin (10(-7)M) for 10 min and the consequent agonist-evoked pressure response was dissipated manually, the response to the same transmural stretch was accompanied by a slowly-developing and prolonged increase in intraluminal pressure. This stretch-activated response was significantly diminished by the stretch-activated cation channel blocker gadolinium (10(-3)M), the L-type Ca(2+) channel blockers nifedipine (2x10(-6)M), diltiazem (10(-5)M), and verapamil (10(-5)M), the sensory neurotoxin capsaicin (10(-5)M), and the NK2-receptor antagonists MEN 10376 (10(-5)M) and SR48968 (3x10(-6)M). These results show the ability of isolated airways to exhibit stretch-activated contractions, and suggest a role for stretch-activated cation channels, sensory afferent neurons, the neurotransmitter NKA, as well as L-type Ca(2+) channels in these isolated airway responses.
Hypertens Res. 2008 Jun; 31(6): 1147-55
Ogawa S, Mori T, Nako K, Ito S
A calcium channel blocker (CCB), azelnidipine (AZ), is reported to inhibit oxidative stresses, particularly when administered under blockade of the renin-angiotensin system (RAS). The purpose of this study was to investigate whether AZ inhibits oxidative stresses more potently than other CCBs under blockade of RAS and exerts renoprotection in type 2 diabetic nephropathy. Subjects were hypertensive type 2 diabetics with nephropathy, taking RAS inhibitors. The patients were randomly assigned to two groups, an AZ group (n=21, 16 mg/d) and a nifedipine-CR (NF) group (n=17, 40 mg/d). The plasma levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), adiponectin and tumor necrosis factor-alpha (TNF(alpha)), the urinary excretion of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) and 8-hydroxydeoxyguanosine (8-OHdG), and the urinary albumin-to-creatinine ratios (ACR) were determined before and after 16-week treatment. Neither metabolic parameters nor blood pressure levels differed between the two groups not only at baseline but also after the treatment. However, significant decreases in MCP-1, IL-6, hsCRP, TNF(alpha), 8-epi-PGF(2alpha), 8-OHdG and ACR levels, and a significant increase in the plasma adiponectin level were detected in the AZ group, but not in the NF group. The % change in the urinary oxidative stress markers correlated with that in ACR. Our results indicate that, in hypertensive patients with diabetic nephropathy, a combination therapy of RAS inhibitors and AZ is an effective therapeutic modality for decreasing not only blood pressure but also inflammations and oxidative stresses.
J Proteome Res. 2008 Aug 21;
Wu X, Chen T, Zheng M, Chen Y, Teng N, Šamaj J, Baluška F, Lin J
Ca (2+) is an essential ion in the control of pollen germination and tube growth. However, the control of pollen tube development by Ca (2+) signaling and its interactions with cytoskeletal components, energy-providing pathways, and cell-expansion machinery remain elusive. Here, we used nifedipine (Nif) to study Ca (2+) functions in differential protein expression and other cellular processes in Pinus bungeana pollen tube growth. Proteomics analysis indicated that 50 proteins showed differential expression with varying doses of Nif. Thirty-four of these were homologous to previously reported proteins and were classified into different functional categories closely related to tip-growth machinery. Blocking the L-type Ca (2+) channel with Nif in the pollen tube membrane induced several early alterations within a short time, including a reduction of extracellular Ca (2+) influx and a subsequently dramatic decrease in cytosolic free Ca (2+) concentration ([Ca (2+)] c), concomitant with ultrastructural abnormalities and changes in the abundance of proteins involved in energy production and signaling. Secondary alterations included actin filament depolymerization, disrupted patterns of endocytosis/exocytosis, and cell wall remodeling, along with changes in the proteins involved in these processes. These results suggested that extracellular Ca (2+) influx was necessary for the maintenance of the typical tip-focused [Ca (2+)] c gradient in the P. bungeana pollen tube, and that reduced adenosine triphosphate production (ATP), depolymerization of the cytoskeleton, and abnormal endocytosis/exocytosis, together with enhanced rigidity of cell walls, were responsible for the growth arrest observed in pollen tubes treated with Nif.
Eur J Pharmacol. 2008 Aug 5;
Zizzo MG, Mulè F, Serio R
Our previous research showed that ATP and adenosine 5'-O-2-thiodiphosphate (ADPbetaS) induce contractile effects in the longitudinal muscle of mouse distal colon via activation of P2Y receptors which are not P2Y(1) or P2Y(12) subtypes. This study investigated the nature of the P2Y receptor subtype(s) and the mechanisms leading to the intracellular calcium concentration increase necessary to trigger muscular contraction. Motor responses of mouse colonic longitudinal muscle to P2Y receptor agonists were examined in vitro as changes in isometric tension. ATP or ADPbetaS induced muscular contraction, which was not affected by P2Y(11) or P2Y(13) selective antagonists. Calcium-free solution or the calcium channel blocker, nifedipine, failed to modify the contractile responses to ATP or ADPbetaS, which were virtually abolished by depletion of calcium intracellular stores after repetitive addition of carbachol in calcium-free medium with addition of cyclopiazonic acid. Neomycin or U-73122, phospholipase C inhibitors, or 2-aminoethoxy-diphenylborate (2-APB), membrane-permeant IP(3) receptor inhibitor reduced the response to ATP, whilst ryanodine or ruthenium red, inhibiting calcium release from ryanodine-sensitive stores, abolished the response to ADPbetaS. Responses to maximally effective concentrations of ATP and ADPbetaS were not fully additive. Desensitisation with ADPbetaS antagonized the contractile effects of ATP, as desensitisation with ATP antagonized the response to ADPbetaS. In the longitudinal muscle of mouse distal colon, ATP and ADPbetaS induce muscular contraction via a P2Y receptor, coupled to differential signal pathways leading to intracellular calcium increase.
Eur J Pharmacol. 2008 Aug 5;
Wu ZX, Yu BP, Xia H, Xu L
Emodin is known to be used in the treatment of cholesterol stones and cholecystitis. This study sought to investigate the effects of emodin on the contraction of gallbladder smooth muscle (GBSM), intracellular Ca(2+) concentration and L-type calcium current in GBSM cells. Gallbladder muscle strips were obtained from adult guinea pigs and the resting tension was recorded. Gallbladder smooth muscle cells were isolated by enzymatic digestion. Cells were loaded with fluo-3/AM and [Ca(2+)](i) was determined by a laser confocal microscope. Calcium current was recorded by the whole-cell patch clamp method. Emodin increased the resting tension of GBSM strips in a dose-dependent manner. Emodin elevated [Ca(2+)](i) in GBSM cells, and this effect was attenuated by pretreatment with nifedipine. In addition, Emodin increased L-type calcium current at concentrations of 1 to 30 microM (at +10 mV, 10 microM, 45.1+/-5.2% compared to control, EC(50) =3.11 microM). In the presence of protein kinase C (PKC) inhibitor, Staurosporine, emodin did not significantly affect the calcium current. However, phorbol 12, 13-dibutyrate mimicked emodin in enhancement of the calcium current. These results suggest that emodin promotes gallbladder contraction by increasing Ca(2+) influx through L-type calcium channel via PKC pathway.
Indian J Exp Biol. 2008 Jan; 46(1): 60-5
Sandhiya S, Dkhar SA, Krishna PR, Ramaswamy S
Prokinetic drugs like mosapride, domperidone etc, are used to treat gastrointestinal delay. Though the receptor-mediated actions of these agents have been studied, involvement of ion channels in reversing morphine-induced gastrointestinal inertia by prokinetic agents has not been explored. Charcoal meal test was used to measure small intestinal transit (SIT) in adult male Swiss albino mice. Animals were given ion channel modifiers and prokinetic drugs intragastrically. Reversal of morphine-induced gastrointestinal delay by mosapride was decreased significantly by CaCl2, minoxidil and glibenclamide. Similarly, domperidone's effect on morphine was decreased by CaCl2, nifedipine, minoxidil and glibenclamide significantly. The results reveal that ion channel modifiers counteract the prokinetic effects of mosapride or domperidone.
Am J Obstet Gynecol. 2008 Aug 7;
Cootauco AC, Murphy JD, Maleski J, Blakemore KJ, Slodzinski MK
OBJECTIVE: The objective of the study was to identify the effect of atrial natriuretic peptide (ANP) on uterine contractility, production of ANP, and natriuretic peptide receptor (NPR) expression in human myometrial tissue. STUDY DESIGN: In an institutional review board-approved study, gravid human myometrium was obtained from patients undergoing cesarean section. Uterine contractility was examined using isometric force tension studies. After regular uterine contractions were obtained with oxytocin, ANP was added in increasing concentrations. ANP concentration was measured from myometrial tissue using radioimmunoassay (RIA). Primary myometrial cell culture was performed and treated with nifedipine vs oxytocin. RIA was performed on these cells and the cell culture media. Western blot analysis was performed on uterine tissue samples for natriuretic peptide receptors. RESULTS: With increasing concentration of ANP (starting at 3 pM), myometrial contraction frequency decreased. ANP was identified in primary cultured myometrial cells and cell culture media. Myometrial ANP concentration increased with advancing gestational age. The concentration of ANP decreased within myometrial cells treated with oxytocin. The amount of ANP in the cell culture media increased from cells treated with nifedipine. Western blot identified NPR-A, -B, and -C in myometrial tissue. NPR-A expression was significantly increased in preterm samples. CONCLUSION: ANP has a dose dependent effect on uterine relaxation. ANP is present in human myometrial cells and appears to be secreted by myometrial cells. The concentration of ANP may vary with gestational age and modulators of uterine contractility. NPR-A, -B, and -C receptor proteins are present in myometrial tissue. NPR-A levels may correlate with gestational age.
Circ Res. 2008 Aug 7;
Jeon ES, Park WS, Lee MJ, Kim YM, Han J, Kim JH
Sphingosylphosphorylcholine (SPC) induces differentiation of human adipose tissue-derived mesenchymal stem cells (hADSCs) to SMCs. In the present study, we characterized contractile and ion channel properties of SMCs differentiated from hADSCs (hADSC-SMCs) as a result of SPC treatment, and we investigated the molecular mechanisms involved in the SPC-induced differentiation. Using in vitro collagen gel lattice contraction and whole cell patch clamp, we showed that the hADSC-SMCs expressed functional L-type voltage-gated Ca(2+) channels and contractile activities in response to KCl, carbachol, and the L-type Ca(2+) channel opener Bay K8644, whereas the L-type Ca(2+) channel blocker nifedipine abrogated the contractility of hADSC-SMCs. Furthermore, hADSC-SMCs expressed functional big conductance Ca(2+)-activated K(+) (BKCa) channels, and the BKCa channel blocker iberiotoxin potentiated the Bay K8644-stimulated contractility of the hADSC-SMCs, indicating that these cells exhibited SMC-like contractile characteristics. SPC-activated RhoA in hADSCs and pretreatment with the Rho kinase inhibitor Y27632 or by overexpression of dominant-negative mutants of RhoA or Rho kinase completely abrogated the SPC-induced differentiation of hADSCs into SMCs. SPC also increased the expression levels of myocardin-related transcription factor (MRTF)-A, a transcription factor involved in smooth muscle differentiation, in hADSCs. Small interference RNA-mediated depletion of endogenous MRTF-A abolished the SPC-induced differentiation of hADSCs into SMCs. Furthermore, SPC promoted nuclear translocation of MRTF-A, and pharmacological inhibition of Rho kinase blocked this effect. These results suggest that SPC induced differentiation of hADSCs into contractile SMCs through a mechanism involving RhoA/Rho kinase-dependent nuclear translocation of MRTF-A.
The effect of nifedipine on the patency of microvascular anastomosis in rats.
Acta Chir Plast. 2008; 50(1): 33-5
Panagiotopoulos KE, Koutsouris M, Panagiotopoulos E, Antonopoulos D, Panagiotopoulos V, Papalois A, Kepenekidis A
Despite advances in microsurgical technique and experience in clinical microvascular surgery, there remains the possibility of vessel thrombosis. Factors that may contribute to vascular pedicle thrombosis include operative trauma, pedicle malposition, kinking, hypercoagulability and arterial vasoconstriction. The purpose of this study was to evaluate the effect of intravenous administration of nifedipine on the patency of the microvascular anastomosis of the femoral artery in rats. A total of 60 rats were used and divided into three groups. The first group (A) was used as a control group with no medical agent, the second group (B) was medicated with heparin, and the third group (C) was medicated with nifedipine. Patency was assessed with the distal empty refill test, one hour (1) and forty-eight hours (48) after completion of the anastomosis. The nifedipine and heparin treated groups (B & C) did not show higher patency rate compared to the control group (A). There was no statistically significant difference of patency percent after 1 hour and 48 hours among the three groups (p = 0.231/p = 0.480). Intravenous administration of nifedipine does not improve the patency of microvascular anastomosis. Surgical technique remains the most important factor for successful microvascular anastomosis.
Can J Cardiol. 2008 Aug; 24(8): 629-32
Bucci C, Mamdani MM, Juurlink DN, Tu JV
BACKGROUND: Dihydropyridine calcium channel blockers are widely used for the treatment of hypertension and angina. Despite safety concerns associated with short-acting agents, increasing evidence supports the safety of long-acting dihydropyridines. Although amlodipine is the best studied of these, there are few studies comparing it with nifedipine. OBJECTIVE: To examine the association between hospitalization for acute coronary syndromes and treatment with amlodipine or extended-release nifedipine in patients 65 years of age and older. The primary objective was a composite of hospital admission for angina or acute myocardial infarction. METHODS: The present population-based, retrospective cohort study used linked health care databases from Ontario. Propensity scores were used to identify highly similar patients started on amlodipine or extended-release nifedipine between April 1997 and March 2002. Time-to-event analysis was conducted using Cox proportional hazards models. RESULTS: The analysis included 24,190 patients (44% male; mean age 75 years) treated with amlodipine or extended-release nifedipine (n=12,095 each). The number of patients reaching the primary end point was 362 (3%) and 294 (2.4%) in the amlodipine and nifedipine groups, respectively. The groups were similar in a large number of demographic and clinical characteristics. No significant differences were observed among users of extended-release nifedipine (adjusted hazard ratio 0.91, 95% CI 0.74 to 1.13) relative to amlodipine. CONCLUSIONS: These findings suggest that amlodipine and extended-release nifedipine are not associated with differential rates of acute coronary events in older patients.