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Effects of verapamil and nifedipine on different parameters in lipopolysaccharide-induced septic shock

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Abstract

Septic shock has a high mortality rate due to the hypotension and circulatory disorder that occurs during its pathogenesis. Recently, humoral factors such as cytokines and nitric oxide became important in the complex pathophysiology of septic shock because there is a close relationship between the determined levels of these humoral factors and the responses to the therapy and survival periods. Verapamil and nifedipine are calcium channel blockers commonly used in the pharmacotherapy of cardiovascular disorders. In the present study these drugs were investigated in the rat septic shock model. In vivo hemodynamic parameters were recorded using a data acquisition system in endotoxin-induced septic shock in rats. The animals were followed for 5 h and blood pressure, rectal temperature, and ECG were recorded. Blood samples were collected at 1 h and 5 h time points after the injection of endotoxin, and serological samples were stored at −25°C. Subsequently, tumor necrosis factor-α, interleukin-10 (enzyme-linked immunosorbent assay), and nitrite (Griess reagent) were determined in these serological samples. Significant correlations were observed between these humoral factors and the disordered hemodynamic factors. A reversal of changes was observed in the levels of serum cytokines, nitrite levels, and hemodynamic parameters with verapamil and nifedipine preadministration (P < 0.05). Additionally, superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) were determined in livers obtained from these animals at the end of the experiments, and these results were compared to hemodynamic parameters and cytokines. Nifedipine and verapamil increased the levels of MDA and SOD but did not change catalase activity.

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References

  1. K Hockerl F Dreher A Kurtz M Bucher (2002) ArticleTitleCyclooxygenase-2 inhibition attenuates lipopolysaccharide-induced cradiovascular failure Hypertension 40 947–953 Occurrence Handle10.1161/01.HYP.0000041221.13644.B9 Occurrence Handle1:CAS:528:DC%2BD38XovFKnsbc%3D

    Article  CAS  Google Scholar 

  2. Y devaux C Seguin S Grosjean N De Talance V Camaeti A Burlet F Zannad C Meistelman PM Metres D Longrois (2001) ArticleTitleLipopolysaccharide-induced increase of prostaglandin E(2) is mediated by inducible nitric oxide synthase activation of the constitutive cyclooxygenase and induction of membrane-associated prostaglandin E synthase J Immunol 167 3962–3971 Occurrence Handle11564815 Occurrence Handle1:CAS:528:DC%2BD3MXntFajtLs%3D

    PubMed  CAS  Google Scholar 

  3. S Cuzzocrea DP Riley AP Caputi D Salvemini (2001) ArticleTitleAntioxidant therapy: a new pharmacological approach in shock, inflammation and ischemia/reperfusion injury Pharmacol Rev 53 135–159 Occurrence Handle11171943 Occurrence Handle1:CAS:528:DC%2BD3MXhsFWqtb0%3D

    PubMed  CAS  Google Scholar 

  4. K Decker (1990) ArticleTitleBiologically active products of stimulated liver macrophages (Kupffer cells) Eur J Biochem 192 245–261 Occurrence Handle2170121 Occurrence Handle1:CAS:528:DyaK3cXlvV2hsbg%3D Occurrence Handle10.1111/j.1432-1033.1990.tb19222.x

    Article  PubMed  CAS  Google Scholar 

  5. MG Clemens M Bauer C Gingalewski E Miescher J Zhang (1994) ArticleTitleHepatic intercellular communication in shock and inflammation Shock 2 1–9 Occurrence Handle7735978 Occurrence Handle1:STN:280:ByqB2MvgtFQ%3D

    PubMed  CAS  Google Scholar 

  6. K Uehara M Nomura Y Ozaki H Fujinaga H Ikefuji M Kimura K Chikamori Y Nakaya S Ito (2003) ArticleTitleHigh-sensitivity C-reactive protein and left ventricular remodeling in patients with acute myocardial infarction Heart Vessels 18 67–74 Occurrence Handle12756602 Occurrence Handle10.1007/s10380-003-0692-2

    Article  PubMed  Google Scholar 

  7. S Price JA Mitchell PB Anning TW Evans (2003) ArticleTitleType II nitric oxide synthase activity is cardioprotective in experimental sepsis Eur J Pharmacol 472 111–118 Occurrence Handle12860479 Occurrence Handle1:CAS:528:DC%2BD3sXlsVams7k%3D Occurrence Handle10.1016/S0014-2999(03)01826-0

    Article  PubMed  CAS  Google Scholar 

  8. T Hijioka RL Rosenberg JJ Lemasters RG Thurman (1992) ArticleTitleKupffer cells contain voltage-dependent calcium channels Mol Pharmacol 41 435–440 Occurrence Handle1372081 Occurrence Handle1:CAS:528:DyaK38XlvVyktLY%3D

    PubMed  CAS  Google Scholar 

  9. MM Sayeed SR Maitra (1987) ArticleTitleEffect of diltiazem on altered cellular calcium regulation during endotoxic shock Am J Physiol 253 R549–R554 Occurrence Handle3310666 Occurrence Handle1:CAS:528:DyaL1cXmtVI%3D

    PubMed  CAS  Google Scholar 

  10. SB Mustafa MS Olson (1999) ArticleTitleEffects of calcium channel antagonists on LPS-induced hepatic iNOS expression Am J Physiol 277 351–360

    Google Scholar 

  11. P Vassalli (1992) ArticleTitleThe pathophysiology of tumor necrosis factors Annu Rev Immunol 10 411–452 Occurrence Handle1590993 Occurrence Handle1:CAS:528:DyaK38XltV2ntLg%3D Occurrence Handle10.1146/annurev.iy.10.040192.002211

    Article  PubMed  CAS  Google Scholar 

  12. RC Newton LP Deccicco (1999) ArticleTitleTherapeutic potential and strategies for inhibiting tumor necrosis factor-α J Med Chem 42 2295–2314 Occurrence Handle10395470 Occurrence Handle1:CAS:528:DyaK1MXktVOktb8%3D Occurrence Handle10.1021/jm980541n

    Article  PubMed  CAS  Google Scholar 

  13. DF Fiorentino A Zlotnik TR Mosmann M Howard A O’Garra (1991) ArticleTitleIL-10 inhibits cytokine production by activated macrophages J Immunol 147 3815–3822 Occurrence Handle1940369 Occurrence Handle1:CAS:528:DyaK38XlslSgug%3D%3D

    PubMed  CAS  Google Scholar 

  14. M Howard T Muchamuel S Andrade S Menon (1993) ArticleTitleInterleukin 10 protects mice from lethal endotoxemia J Exp Med 177 1205–1208 Occurrence Handle8459215 Occurrence Handle1:CAS:528:DyaK3sXhsVGkt7s%3D Occurrence Handle10.1084/jem.177.4.1205

    Article  PubMed  CAS  Google Scholar 

  15. H Hirota M Izumi T Hamaguchi S Sugiyama E Murakami K Kunisada Y Fujio Y Oshima Y Nakaoka K Yamauchi-Takihara (2004) ArticleTitleCirculating interleukin-6 family cytokines and their receptors in patients with congestive heart failure Heart Vessels 19 237–241 Occurrence Handle15372299 Occurrence Handle10.1007/s00380-004-0770-z

    Article  PubMed  Google Scholar 

  16. SC Wu CP Liu HT Chiang SL Lin (2004) ArticleTitleProspective and randomized study of the antihypertensive effect and tolerability of three antihypertensive agents, losartan, amlodipine, and lisinopril, in hypertensive patients Heart Vessels 19 13–18 Occurrence Handle14685749 Occurrence Handle10.1007/s00380-003-0724-x

    Article  PubMed  Google Scholar 

  17. SN Lichtman J Wang JH Schwab JJ Lemasters (1994) ArticleTitleComparison of peptidoglycan-polysaccharide and lipopolysaccharide stimulation of Kupffer cells to produce tumor necrosis factor and interleukin-1 Hepatology 19 1013–1022 Occurrence Handle8138241 Occurrence Handle1:CAS:528:DyaK2cXktVOjsrg%3D Occurrence Handle10.1016/0270-9139(94)90303-4

    Article  PubMed  CAS  Google Scholar 

  18. SN Lichtman J Wang C Zhang JJ Lemasters (1996) ArticleTitleEndocytosis and Ca2+ are required for endotoxin-stimulated TNF-alpha release by rat Kupffer cells Am J Physiol 271 920–928

    Google Scholar 

  19. DS Bredt SH Snyder (1994) ArticleTitleNitric oxide, a physiologic messenger molecule Annu Rev Biochem 63 175–195 Occurrence Handle7526779 Occurrence Handle1:CAS:528:DyaK2cXmsFWrsrw%3D Occurrence Handle10.1146/annurev.bi.63.070194.001135

    Article  PubMed  CAS  Google Scholar 

  20. C Can B Demirci A Uysal YD Akcay S Kosay (2003) ArticleTitleContradictory effects of chlorpromazine on endothelial cells in a rat model of endotoxic shock in association with its actions on serum TNF-alpha levels and antioxidant enzyme activities Pharmacol Res 48 223–230 Occurrence Handle12860438 Occurrence Handle1:CAS:528:DC%2BD3sXltl2hu7Y%3D Occurrence Handle10.1016/S1043-6618(03)00093-8

    Article  PubMed  CAS  Google Scholar 

  21. OH Lowry NJ Rosebrough AL Farr RJ Randall (1951) ArticleTitleProtein measurement with the Folin phenol reagent J Biol Chem 193 265–275 Occurrence Handle14907713 Occurrence Handle1:CAS:528:DyaG38XhsVyrsw%3D%3D

    PubMed  CAS  Google Scholar 

  22. D Altavilla G Squadrito L Minutoli B Deodato A Bova A Sardella P Seminara M Passaniti G Urna SF Venuti AP Caputi F Squadrito (2002) ArticleTitleInhibition of nuclear factor-kappaB activation by IRFI 042, protects against endotoxin-induced shock Cardiovasc Res 54 684–693 Occurrence Handle12031715 Occurrence Handle1:CAS:528:DC%2BD38XjvVSgu7c%3D Occurrence Handle10.1016/S0008-6363(02)00276-6

    Article  PubMed  CAS  Google Scholar 

  23. M Saitoh T Osanai T Kamada T Matsunaga H Ishizaka H Hanada K Okumura (2003) ArticleTitleHigh plasma level of asymmetric dimethylarginine in patients with acutely exacerbated congestive heart failure: role in reduction of plasma nitric oxide level Heart Vessels 18 177–182 Occurrence Handle14520484 Occurrence Handle10.1007/s00380-003-0715-y

    Article  PubMed  Google Scholar 

  24. CA Dinarello (1991) ArticleTitleThe proinflammatory cytokines interleukin-1 and tumor necrosis factor and treatment of the septic shock syndrome J Infect Dis 163 1177–1184 Occurrence Handle2037782 Occurrence Handle1:CAS:528:DyaK3MXltFahsLk%3D

    PubMed  CAS  Google Scholar 

  25. N Yamanoto F Sakai H Yamazaki N Sato K Nakahara M Okuhara (1997) ArticleTitleFR167653, a dual inhibitor of interleukin-1 and tumor necrosis factor-alpha, ameliorates endotoxin induced shock Eur J Pharmacol 327 169–174 Occurrence Handle10.1016/S0014-2999(97)89657-4

    Article  Google Scholar 

  26. RG Kilbourn OW Griffith (1992) ArticleTitleOverproduction of nitric oxide in cytokine-mediated and septic shock J Natl Cancer Inst 84 827–831 Occurrence Handle1375655 Occurrence Handle1:STN:280:By2B2sjmvVc%3D

    PubMed  CAS  Google Scholar 

  27. JJ Zimmerman (1995) ArticleTitleDefining the role of oxyradicals in the pathogenesis of sepsis Crit Care Med 23 616–617 Occurrence Handle7712748 Occurrence Handle1:STN:280:ByqB38fjtlc%3D Occurrence Handle10.1097/00003246-199504000-00003

    Article  PubMed  CAS  Google Scholar 

  28. QW Xie Y Kashiwabara C Nathan (1994) ArticleTitleRole of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase J Biol Chem 269 4705–4708 Occurrence Handle7508926 Occurrence Handle1:CAS:528:DyaK2cXitV2qu74%3D

    PubMed  CAS  Google Scholar 

  29. U Forstermann HH Schmidt JS Pollock H Sheng JA Mitchell TD Warner M Nakane F Murad (1991) ArticleTitleIsoforms of nitric oxide synthase. Characterization and purification from different cell types Biochem Pharmacol 42 1849–1857 Occurrence Handle1720618 Occurrence Handle1:CAS:528:DyaK38XisFOi Occurrence Handle10.1016/0006-2952(91)90581-O

    Article  PubMed  CAS  Google Scholar 

  30. DS Winlaw GA Smythe AM Keogh CG Schyvens PM Spratt PS Macdonald (1995) ArticleTitleNitric oxide production and heart failure Lancet 345 390–391 Occurrence Handle7845142 Occurrence Handle1:STN:280:ByqC2cjmtF0%3D Occurrence Handle10.1016/S0140-6736(95)90379-8

    Article  PubMed  CAS  Google Scholar 

  31. C Szabo JA Mitchell SS Gross C Thiemermann JR Vane (1993) ArticleTitleNifedipine inhibits the induction of nitric oxide synthase by bacterial lipopolysaccharide J Pharmacol Exp Ther 265 674–680 Occurrence Handle7684445 Occurrence Handle1:CAS:528:DyaK3sXks1akt78%3D

    PubMed  CAS  Google Scholar 

  32. WZ Wang A Matsumori T Yamada T Shioi I Okada S Matsui Y Sato H Suzuki K Shiota S Sasayama (1997) ArticleTitleBeneficial effects of amlodipine in a murine model of congestive heart failure induced by viral myocarditis. A possible mechanism through inhibition of nitric oxide production Circulation 7 IssueID95 245–251

    Google Scholar 

  33. M Tokac A Ozeren M Aktan BB Altunkeser K Ozdemir A Duzenli H Gok (2003) ArticleTitleThe role of inflammation markers in triggering acute coronary events Heart Vessels 18 171–176 Occurrence Handle14520483 Occurrence Handle10.1007/s00380-003-0708-x

    Article  PubMed  Google Scholar 

  34. TC Chou SP Yang D Pei (2002) ArticleTitleAmlodipine inhibits pro-inflammatory cytokines and free radical production and inducible nitric oxide synthase expression in lipopolysaccharide/interferon-gamma-stimulated cultured vascular smooth muscle cells Jpn J Pharmacol 89 157–163 Occurrence Handle12120758 Occurrence Handle1:CAS:528:DC%2BD38XkvV2htLw%3D Occurrence Handle10.1254/jjp.89.157

    Article  PubMed  CAS  Google Scholar 

  35. A Matsumori K Ono R Nishio Y Nose S Sasayama (2000) ArticleTitleAmlodipine inhibits the production of cytokines induced by ouabain Cytokine 12 294–297 Occurrence Handle10704258 Occurrence Handle1:CAS:528:DC%2BD3cXhsFSqtLw%3D Occurrence Handle10.1006/cyto.1999.0555

    Article  PubMed  CAS  Google Scholar 

  36. A Matsumori K Ono R Nishio H Igata T Shioi S Matsui Y Furukawa A Iwasaki Y Nose S Sasayama (1997) ArticleTitleModulation of cytokine production and protection against lethal endotoxemia by the cardiac glycoside ouabain Circulation 2 IssueID96 1501–1506

    Google Scholar 

  37. A Matsumori (1997) ArticleTitleMolecular and immune mechanisms in the pathogenesis of cardiomyopathy role of viruses, cytokines, and nitric oxide Jpn Circ J 61 275–291 Occurrence Handle9152779 Occurrence Handle1:CAS:528:DyaK2sXktFGqt7k%3D Occurrence Handle10.1253/jcj.61.275

    Article  PubMed  CAS  Google Scholar 

  38. IT Mak WB Weglicki (1994) ArticleTitleAntioxidant activity of calcium channel blocking drugs Methods Enzymol 234 620–630 Occurrence Handle7808338 Occurrence Handle1:CAS:528:DyaK2MXhvFOlsbY%3D Occurrence Handle10.1016/0076-6879(94)34133-8

    Article  PubMed  CAS  Google Scholar 

  39. K Hishikawa TF Luscher (1998) ArticleTitleFelodipine inhibits free-radical production by cytokines and glucose in human smooth muscle cells Hypertension 32 1011–1015 Occurrence Handle9856965 Occurrence Handle1:CAS:528:DyaK1MXitVWjtQ%3D%3D

    PubMed  CAS  Google Scholar 

  40. V Ben-Shaul Y Sofer M Bergman Y Zurovsky S Grossman (1999) ArticleTitleLipopolysaccharide-induced oxidative stress in the liver comparison between rat and rabbit Shock 12 288–293 Occurrence Handle10509631 Occurrence Handle1:STN:280:DyaK1Mvjslegsg%3D%3D

    PubMed  CAS  Google Scholar 

  41. Malefyt R de Waal J Abrams B Bennett CG Figdor JE De Vries (1991) ArticleTitleInterleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes, an autoregulatory role of IL-10 produced by monocytes J Exp Med 174 1209–1220 Occurrence Handle10.1084/jem.174.5.1209

    Article  Google Scholar 

  42. A Matsumori Y Numokawa S Sasayama (2000) ArticleTitleNifedipine inhibits activation of transcription factor NF-kappaB Life Sci 67 2655–2661 Occurrence Handle11104367 Occurrence Handle1:CAS:528:DC%2BD3cXnslaitrY%3D Occurrence Handle10.1016/S0024-3205(00)00849-3

    Article  PubMed  CAS  Google Scholar 

  43. J Cuschieri D Gourlay I Garcia S Jelacic RV Maier (2002) ArticleTitleSlow channel calcium inhibition blocks proinflammatory gene signaling and reduces macrophage responsiveness J Trauma 52 434–442 Occurrence Handle11901316 Occurrence Handle1:CAS:528:DC%2BD38Xis1alsLs%3D Occurrence Handle10.1097/00005373-200203000-00004

    Article  PubMed  CAS  Google Scholar 

  44. M Roth R Keul LR Emmons WH Horl LH Block (1992) ArticleTitleManidipine regulates the transcription of cytokine genes Proc Natl Acad Sci USA 1 IssueID89 4071–4075

    Google Scholar 

  45. L Cominacini U Garbin A Fratta Pasini T Paulon A Davoli M Campagnola E Marchi AM Pastorino G Gaviraghi V Lo Cascio (1997) ArticleTitleLacidipine inhibits the activation of the transcription factor NF-kappaB and the expression of adhesion molecules induced by pro-oxidant signals on endothelial cells J Hypertens 15 1633–1640 Occurrence Handle9488215 Occurrence Handle1:CAS:528:DyaK1cXoslaqsA%3D%3D Occurrence Handle10.1097/00004872-199715120-00065

    Article  PubMed  CAS  Google Scholar 

  46. O Eickelberg M Roth R Mussmann JJ Rudiger M Tamm AP Perruchoud LH Block (1999 May) ArticleTitleCalcium channel blockers activate the interleukin-6 gene via the transcription factors NF-IL6 and NF-kappaB in primary human vascular smooth muscle cells Circulation 4 IssueID99 2276–2282

    Google Scholar 

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Sirmagul, B., Kilic, F., Tunc, Ö. et al. Effects of verapamil and nifedipine on different parameters in lipopolysaccharide-induced septic shock. Heart Vessels 21, 162–168 (2006). https://doi.org/10.1007/s00380-005-0874-0

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