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Effects of calcium channel blockers on hyaluronidase-induced capillary vascular permeability

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Abstract

Inflammation and increased capillary permeability is a significant aspect of the pathogenesis of many diseases including atherosclerosis. L-type calcium channel blockers (CCB) are commonly used as cardiovascular drugs. Amlodipine, lacidipine, and nicardipine were evaluated for anti-inflammatory activity on the paw oedema produced by carrageenan. The effect of these drugs was compared with the activity of indomethacin. Their effects on vascular permeability were also tested by hyaluronidase-induced capillary permeability. In our animal experiments, amlodipine decreased the carrageenan-induced paw oedema at doses of 1, 3, and 6 mg kg−1 by 27.3%, 43.7%, and 67.3% four hour after carrageenan administration; the same doses of lacidipine and nicardipine decreased paw oedema by 37.1%, 55.6%, 76.4%, 11.2%, 31.0%, 91%; and indomethacin decreased oedema by 38.2% at a dose of 6 mg kg−1. Lacidipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at doses of 1, 3, and 6 mg kg−1 compared with the control group. However, amlodipine and nicardipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at 3 and 6 mg kg−1 doses. A 6 mg kg−1 dose of indomethacin significantly decreased the capillary permeability which was increased by hyaluronidase. These results suggest that CCBs can be efficient anti-inflammatories, and can also significantly decrease capillary permeability.

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References

  • Abernethy, D. R. and Schwartz, J. B., Calcium-antagonist drugs. N Engl J Med., 341, 1447–1457 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Aditya, G. N., Chattopadhyay, R. N., Mandal, S., Roy, R. K., Lahiri, H. L., Maitra, S. K. et al., Preliminary study on antiinflammatory effect of calcium channel blockers in albino rats. Indian Journal of Pharmacology., 29, 132–134 (1997).

    CAS  Google Scholar 

  • Al-Naemi, H. and Baldwin, A. L., Nitric oxide protects venules against histamine-induced leaks. Microcirculation, 7, 215–223 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Bilici, D., Akpinar, E., Gursan, N., Dengiz, G. O., Bilici, S., and Atlas, S., Protective effect of T-type calcium channel blocker in histamine-induced paw inflammation in rat. Pharmacol Res., 44, 527–531 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Carnevale, K. A. and Cathcart, M., Calcium-independent phospholipase A(2) is required for human monocyte chemotaxis to monocyte chemoattractant protein 1. J Immunol., 167, 3414–3421 (2001).

    PubMed  CAS  Google Scholar 

  • Chand, N., Pillar, J., Diamantis, W., and Sofia, R. D., In vitro inhibition of allergic histamine release by calcium antagonists. Eur J Pharmacol., 107, 353–358 (1985).

    Article  PubMed  CAS  Google Scholar 

  • Chen, L., Haught, W. H., Yang, B., Saldeen, T. G., Parathasarathy, S., and Mehta, J. L., Preservation of endogenous antioxidant activity and inhibition of lipid peroxidation as common mechanisms of antiatherosclerotic effects of vitamin E, lovastatin and amlodipine. J Am Coll Cardiol., 30, 569–575 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Cominacini, L., Pasini, A. F., Pastorino, A. M., Garbin, U., Davoli, A., Rigoni, A. et al., Comparative effects of different dihydropyridines on the expression of adhesion molecules induced by TNF-alpha on endothelial cells. J Hypertens., 17, 1837–1841 (1999).

    Article  PubMed  CAS  Google Scholar 

  • De Souza, A. P., Tanowitz, H. B., Chandra, M., Shtutin, V., Weiss, L. M., Morris, S. A. et al., Effects of early and late verapamil administration on the development of cardiomyopathy in experimental chronic Trypanosoma cruzi (Brazil strain) infection. Parasitol Res., 92, 496–501 (2004).

    Article  PubMed  Google Scholar 

  • El-Bizri, N., Bkaily, G., Wang, S., Jacques, D., Regoli, D., D’Orleans-Juste, P. et al., Bradykinin induced a positive chronotropic effect via stimulation of T-and L-type calcium currents in heart cells. Can J Physiol Pharmacol., 81, 247–258 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Elferink, J. G., Boonen, G. J., and De Koster, B. M., The role of calcium in neutrophil migration: the effect of calcium and calcium-antagonists in electroporated neutrophils. Biochem Biophys Res Commun., 31, 864–869 (1992).

    Article  Google Scholar 

  • Elferink, J. G., Interference of the calcium antagonists verapamil and nifedipine with lysosomal enzyme release from rabbit polymorphonuclear leukocytes. Arzneimittelforschung, 32, 1417–1420 (1982).

    PubMed  CAS  Google Scholar 

  • Fuster, V., Badimon, L., Badimon, J. J., and Chesebro, J. H., The pathogenesis of coronary artery disease and the acute coronary syndromes (2). New Engl. J. Med., 326, 310–318 (1992).

    PubMed  CAS  Google Scholar 

  • Grossman, E. and Meserli, F. H., Calcium antagonists. Prog Cardiovasc Dis., 47, 34–57 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Gurdal, H., Sara, Y., and Tulunay, F. C., Effects of calcium channel blockers on formalin-induced nociception and inflammation in rats. Pharmacology., 44, 290–296 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Henry, P. D., Atherosclerosis, calcium, and calcium antagonists. Circulation, 72, 456–459 (1985).

    PubMed  CAS  Google Scholar 

  • Henry, P. D. and Bentley, K., Suppression of atherosclerosis in cholesterol-fed rabbits treated with nifedipine. J Clin Invest., 68, 1366–1369 (1989).

    Article  Google Scholar 

  • Houck, J. C. and Chang, C. M., Permeability factor contaminating hyaluronidase preparations. Inflammation, 3, 447–451 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Huang, Q. and Yuan, Y., Interaction of PKC and NOS in signal transduction of microvascular hyperpermeability. Am J Physiol., 273, 42–2451 (1997).

    Google Scholar 

  • Janssen, B. J., Kam, K. L., and Smits, J. F., Preferential renal and mesenteric vasodilation induced by barnidipine and amlodipine in spontaneously hypertensive rats. Naunyn Schmiedebergs Arch Pharmacol., 364, 14–421 (2001).

    Article  Google Scholar 

  • Kouoh, F., Gressier, B., Dine, T., Luyckx, M., Brunet, C., and Ballester, L., Antioxidant effects and anti-elastase activity of the calcium antagonist nicardipine on activated human and rabbit neutrophils-a potential antiatherosclerotic property of calcium antagonists. Cardiovasc Drugs Ther., 16, 515–520 (2006).

    Article  Google Scholar 

  • Kramsch, D. M., Limits of lipid-lowering therapy: the potential benefits of amlodipine as an antiatherosclerotic agent. Int J Cardiol., 62, 119–124 (1997).

    Article  Google Scholar 

  • Leslie, C. C., Properties and regulation of cytosolic phospholipase A2. J Biol Chem., 272, 16709–16712 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Liao, F., Andalibi, A., Qiao, J. H., Allayee, H., Fogelman, A. M., and Lusis, A. J., Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction, and aortic fatty streak formation in mice. J Clin Invest., 94, 877–884 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Libby, P., Molecular bases of the acute coronary syndromes. Circulation, 91, 2844–2850 (1995).

    PubMed  CAS  Google Scholar 

  • Martinez, L. L., Aparecida, De Oliveira, M., and Fortes, Z. B., Influence of verapamil and diclofenac on leukocyte migration in rats. Hypertension., 34, 997–1001 (1999).

    PubMed  CAS  Google Scholar 

  • Marzocco, S., Di Paola, R., Serraino, I., Sorrentino, R., Meli, R., and Mattaceraso, G., Effect of methylguanidine in carrageenan-induced acute inflammation in the rats. Eur J Pharmacol., 26, 341–350 (2004).

    Article  Google Scholar 

  • Maslinska, D. and Gajewski, M., Some aspects of the inflammatory process. Folia Neuropathol., 36, 199–204 (1998).

    PubMed  CAS  Google Scholar 

  • Mason, R. P., Cytoprotective properties of a long-acting calcium channel blocker: new mechanism of action. Am J Hypertension., 11, 245A (1998).

    Article  Google Scholar 

  • Mason, R. P., Walter, M. F., Trumbore, M. W., Olmstead, E. G. Jr., and Mason, P. E., Membrane antioxidant effects of the charged dihydropyridine calcium antagonist amlodipine. J Mol Cell Cardiol., 31, 275–281 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Mohler, E. R 3rd, Sorensen, L. C., Ghali, J. K., Schocken, D. D., Willis, P. W., and Bowers, J. A., Role of cytokines in the mechanism of action of amlodipine: the PRAISE Heart Failure Trial Prospective Randomized Amlodipine Survival Evaluation. J Am Coll Cardiol., 30, 35–41 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Neto, A. G., Costa, J. M., Belati, C. C., Vinholis, A. H., Possebom, L. S., Da Silva, and Filho, A. A., Analgesic and anti-inflammatory activity of a crude root extract of Pfaffia glomerata (Spreng) Pedersen. J Ethnopharmacol., 96, 87–91 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Oates, J. A. and Brown, N. J., Drugs affecting renal and cardiovascular function: Antihypertensive Agents and the Drug Therapy of Hypertension. In: Brunton L, editor. Godman and Gilman’s the pharmacological basis of therapeutics. New-York: Mc Graw-Hill; pp. 671–717 (2006)

    Google Scholar 

  • Pitt, B., Byington, R. P., Furberg, C. D., Hunninghake, D. B., Mancini, G. B., Miller, M. E. et al., Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation., 102, 1503–151 (2000).

    PubMed  CAS  Google Scholar 

  • Procida, C., Mantovani, V., and Bianchini, P., Anti-hyaluronidase activity of some pyrazole derivatives. Boll Soc Ital Biol Sper., 47, 159–163 (1971).

    PubMed  CAS  Google Scholar 

  • Ramprasath, V. R., Shanthi, P., and Sachdanandam, P., Antiinflammatory effect of Semecarpus anacardium Linn. Nut extract in acute and chronic inflammatory conditions. Biol Pharm Bull., 27, 2028–2031 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Ross, R., Atherosclerosis an inflammatory disease. N Engl J Med, 340, 115–126 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Salomone, S., Silva, C. L., Morel, N., and Godfraind, T., Facilitation of the vasorelaxant action of calcium antagonists by basal nitric oxide in depolarized artery. Naunyn Schmiedebergs Arch Pharmacol., 354, 505–512 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Siflinger-Birnboim, A., Lum, H., Del Vecchio, P. J., Malik, A. B., Involvement of Ca2+ in the H2O2-induced increase in endothelial permeability. Am J Physiol., 270, 973–978 (1996).

    Google Scholar 

  • Siflinger-Birnboim, A. and Malik, A. B., Regulation of endothelial permeability by second messengers. New Horiz., 4, 87–98 (1996).

    PubMed  CAS  Google Scholar 

  • Sirmagul, B., Kilic, F. S., Batu, O., and Erol, K., The effects of verapamil on stress-and histamine-induced gastric lesions in rats. Methods Find Exp Clin Pharmacol., 26, 763 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Suleyman, H., Gul, H. I., and Asoglu, M., Anti-inflammatory activity of 3-benzoyl-1-methyl-4-phenyl-4-piperidinol hydrochloride. Pharmacol Res., 47, 471–475 (1998).

    Article  Google Scholar 

  • Suleyman, H., Demirezer, L.O., Kuruuzum., Banoglu, Z. N., Gocer, F., and Ozbakir, G., Antiinflammatory effect of the aqueous extract from Rumex patientia L. roots. J Ethnopharmacol., 65, 141–148 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Suleyman, H., Odabasoglu, F., Aslan, A., Cakir, A., Karagoz, Y., and Gocer, F., Anti-inflammatory and antiulcerogenic effects of the aqueous extract of Lobaria pulmonaria (L.) Hoffm. Phytomedicine., 10, 552–557 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Suleyman, H., Halici, Z., Hacmuftuoglu, A., and Gocer, F., Role of adrenal gland hormones in antiinflammatory effect of calcium channel blockers. Pharmacol Rep., 58, 692–699 (2006).

    PubMed  CAS  Google Scholar 

  • Suleyman, H., Gul, H. I., Gul, M., Alkan, M., and Gocer, F., Antiinflammatory activity of bis(3-aryl-3-oxo-propyl)methylamine hydrochloride in rat. Biol Pharm Bull., 30, 63–67 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Tulenko, T. N., Laury-Kleintop, L., Walter, M. F., and Mason, R. P., Cholesterol, calcium and atherosclerosis: Is there a role forcalcium channel blockers in atheroprotection? Int J Cardiol., 62, 55–66 (1997).

    Article  Google Scholar 

  • Tulenko, T. N., Step, D. W., Chen, M. et al., Actions of the charged dihydropyridine amlodipine in a cell culture model of dietary atherosclerosis. J Cardiovasc Pharmacol, 126, 11–17 (1995).

    Google Scholar 

  • Winter, C. A., Risley, E. A., and Nuss, G. W., Carrageenininduced edema in hind paw of the rat as an assay for antiiflammatory drugs. Proc Soc Exp Biol Med., 111, 544–547 (1962).

    PubMed  CAS  Google Scholar 

  • Van Zwieten, P. A., The pharmacological properties of lipophilic calcium antagonists. Blood Pres., 2, 5–9 (1998).

    Google Scholar 

  • Yamada, Y., Yokota, M., Furumichi, T., Furui, H., Yamauchi, K., and Saito, H., Protective effects of calcium channel blockers on hydrogen peroxide induced increases in endothelial permeability. Cardiovasc Res., 24, 993–997 (1990).

    Article  PubMed  CAS  Google Scholar 

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Halici, Z., Suleyman, H. & Cadirci, E. Effects of calcium channel blockers on hyaluronidase-induced capillary vascular permeability. Arch. Pharm. Res. 31, 891–899 (2008). https://doi.org/10.1007/s12272-001-1243-0

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