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Influence of cilnidipine or nisoldipine on sympathetic activity in healthy male subjects

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Abstract

The aim of this study was to investigate whether cilnidipine, an N- and L-type calcium channel blocker, and nisoldipine, an L-type calcium channel blocker, have different effects on sympathetic activity, using an identical group of healthy male subjects. Eight healthy men (22–28 years) were given 10 mg of cilnidipine or 10 mg of nisoldipine in a randomized crossover design. In each trial, in subjects without medication on day 1 (control) and with medication on day 2, we measured heart rate (HR), low frequency (LF)/high frequency (HF) of HR variability, and plasma noradrenaline (NA) in a resting supine position and during head-up tilt, and palmar sweating during a mental arithmetic test, before and at 1, 2, 4, 6, and 8 h after administration. Time-plasma concentration profiles of the two drugs were similar. Measurements in controls on the two days showed no significant difference in any of these parameters. Nisoldipine, but not cilnidipine, slightly increased HR and LF/HF at rest. Head-up tilt increased HR, LF/HF, and plasma NA. As evaluated with repeated-measures analysis of variance, head-up tilt induced a significant increase in LF/HF, but not HR or plasma NA, and the effect of cilnidipine was significantly less than that of nisoldipine (P = 0.017). Postural hypotension was not observed. There was no difference in mental arithmetic-induced sweating between the two drugs. Cilnidipine, but not nisoldipine, might have a weak inhibitory effect on reflex sympathetic activity.

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References

  1. JM Nooney RC Lambert A Feltz (1997) ArticleTitleIdentifying neuronal non-L Ca2+ channels: more than stamp collection? Trends Pharmacol Sci 18 363–371 Occurrence Handle9357321 Occurrence Handle1:STN:280:DyaK1c%2FitVWqsw%3D%3D

    PubMed  CAS  Google Scholar 

  2. RW Tsein PT Ellinor WA Horne (1991) ArticleTitleMolecular diversity of voltage-dependent Ca2+ channels Trends Pharmacol Sci 12 349–354 Occurrence Handle10.1016/0165-6147(91)90595-J

    Article  Google Scholar 

  3. LD Hirning AP Fox EW McCleskey BM Olivera SA Thayer RJ Miller RW Tsien (1988) ArticleTitleDominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons Science 239 57–61 Occurrence Handle2447647 Occurrence Handle10.1126/science.2447647 Occurrence Handle1:CAS:528:DyaL1cXkvF2iuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  4. Y Fujita M Mynlieff RT Dirksen MS Kim T Nidome J Nakai T Friedrich N Iwabe T Miyata T Furuchi D Furutama K Mikoshiba Y Mori KG Beam (1993) ArticleTitlePrimary structure and functional expression of the ω-conotoxin-sensitive N-type calcium channel from rat brain Neuron 10 585–598 Occurrence Handle8386525 Occurrence Handle10.1016/0896-6273(93)90162-K Occurrence Handle1:CAS:528:DyaK3sXmtF2rs7s%3D

    Article  PubMed  CAS  Google Scholar 

  5. D Sarsero T Fujiwara P Molenaar JA Angus (1998) ArticleTitleHuman vascular to cardiac tissue selectivity of L- and T-type calcium channel antagonists Br J Pharmacol 125 109–119 Occurrence Handle9776350 Occurrence Handle10.1038/sj.bjp.0702045 Occurrence Handle1:CAS:528:DyaK1cXmtlCmtbk%3D

    Article  PubMed  CAS  Google Scholar 

  6. CD Furberg BM Psaty JV Meyer (1995) ArticleTitleNifedipine. Dose-related increase in mortality in patients with coronary heart disease Circulation 92 1326–1331 Occurrence Handle7648682 Occurrence Handle1:CAS:528:DyaK2MXosF2mtr0%3D

    PubMed  CAS  Google Scholar 

  7. E Grossman FH Messerli (1997) ArticleTitleEffect of calcium antagonists on plasma norepinephrine levels, heart rate, and blood pressure Am J Cardiol 80 1453–1458 Occurrence Handle9399721 Occurrence Handle10.1016/S0002-9149(97)00722-4 Occurrence Handle1:CAS:528:DyaK2sXotFWjs7k%3D

    Article  PubMed  CAS  Google Scholar 

  8. J de Champlain M Karas P Nguyen P Cartier R Wistaff CB Toal R Nadeau P Larochelle (1998) ArticleTitleDifferent effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients J Hypertens 16 1357–1369 Occurrence Handle10.1097/00004872-199816090-00017 Occurrence Handle1:CAS:528:DyaK1cXmtFKqsbw%3D

    Article  CAS  Google Scholar 

  9. JA Angus CE Wright Q Xi (2000) ArticleTitleTargetting voltage-gated calcium channels in cardiovascular therapy Lancet 356 1287–1289 Occurrence Handle11073011 Occurrence Handle10.1016/S0140-6736(00)02807-5 Occurrence Handle1:STN:280:DC%2BD3crhsVSmuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  10. CE Wright AL Hawkes JA Angus (2000) ArticleTitlePostural hypotension following N-type Ca2+ channel blockade is amplified in experimental hypertension J Hypertens 18 65–73 Occurrence Handle10678545 Occurrence Handle10.1097/00004872-200018010-00010 Occurrence Handle1:CAS:528:DC%2BD3cXhtFaqs74%3D

    Article  PubMed  CAS  Google Scholar 

  11. SL Whorlow JA Angus CE Wright (1996) ArticleTitleSelectivity of ω-conotoxin GVIA for N-type calcium channels in rat isolated small mesenteric arteries Clin Exp Pharmacol Physiol 23 16–21 Occurrence Handle8713491 Occurrence Handle10.1111/j.1440-1681.1996.tb03036.x Occurrence Handle1:CAS:528:DyaK28XksVCqt74%3D

    Article  PubMed  CAS  Google Scholar 

  12. R Yoshimoto H Dohmoto K Yamada A Goto (1991) ArticleTitleProlonged inhibition of vascular contraction and calcium influx by the novel 1,4-dihydropyridine calcium antagonist cilnidipine Jpn J Pharmacol 56 225–229 Occurrence Handle1881002 Occurrence Handle1:CAS:528:DyaK3MXks1Cnsr0%3D Occurrence Handle10.1254/jjp.56.225

    Article  PubMed  CAS  Google Scholar 

  13. H Uneyama A Takahara H Dohmoto R Yoshimoto K Inoue N Akaike (1997) ArticleTitleBlockade of N-type Ca2+ current by cilnidipine (FRC-8653) in acutely dissociated rat sympathetic neurons Br J Pharmacol 122 37–42 Occurrence Handle9298526 Occurrence Handle10.1038/sj.bjp.0701342 Occurrence Handle1:CAS:528:DyaK2sXmt1ajtr8%3D

    Article  PubMed  CAS  Google Scholar 

  14. S Fujii K Kameyama M Hosono Y Hayashi K Kitamura (1997) ArticleTitleEffect of cilnidipine, a novel dihydropyridine Ca++-channel antagonist, on N-type Ca++ channel in rat dorsal root ganglion neurons J Pharmacol Exp Ther 280 1184–1191 Occurrence Handle9067302 Occurrence Handle1:CAS:528:DyaK2sXhvF2mt7s%3D

    PubMed  CAS  Google Scholar 

  15. M Hosono S Fujii T Hiruma K Watanabe Y Hayashi H Ohnishi Y Takata H Kato (1995) ArticleTitleInhibitory effect of cilnidipine on vascular sympathetic neurotransmission and subsequent vasoconstriction in spontaneously hypertensive rats Jpn J Pharmacol 69 127–134 Occurrence Handle8569049 Occurrence Handle1:CAS:528:DyaK2MXovFyrt74%3D

    PubMed  CAS  Google Scholar 

  16. A Nap MJ Mathy JC Balt M Pfaffendorf PA van Zweiten (2004) ArticleTitleThe evaluation of the N-type channel blocking properties of cilnidipine and other voltage-dependent calcium antagonists Fundam Clin Pharmacol 18 309–319 Occurrence Handle15147282 Occurrence Handle10.1111/j.1472-8206.2004.00236.x Occurrence Handle1:CAS:528:DC%2BD2cXkvFClsbk%3D

    Article  PubMed  CAS  Google Scholar 

  17. S Akselrod D Gordon FA Ubel DC Shannon AC Berger RJ Cohen (1981) ArticleTitlePower spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control Science 213 220–222 Occurrence Handle6166045 Occurrence Handle10.1126/science.6166045 Occurrence Handle1:STN:280:DyaL3M3isFyhsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  18. F Badilini P Maison-Blanche P Coumel (1998) ArticleTitleHeart rate variability in passive tilt test: comparative evaluation of autoregressive and FFT spectral analyses Pacing Clin Electrophysiol 21 1122–1132 Occurrence Handle9604245 Occurrence Handle10.1111/j.1540-8159.1998.tb00159.x Occurrence Handle1:STN:280:DyaK1c3mslKjtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  19. S Homma Y Nakajima S Toma T Ito T Shibata (1998) ArticleTitleIntracerebral source localization of mental process-related potentials elicited prior to mental sweating response in humans Neurosci Lett 247 25–28 Occurrence Handle9637401 Occurrence Handle10.1016/S0304-3940(98)00274-2 Occurrence Handle1:CAS:528:DyaK1cXisFakur4%3D

    Article  PubMed  CAS  Google Scholar 

  20. F Kato K Saga Y Morimoto R Kaneko (1999) ArticleTitlePilocarpine-induced cholinergic sweat secretion compared with emotional sweat secretion in atopic dermatitis Br J Dermatol 140 1110–1113 Occurrence Handle10354079 Occurrence Handle10.1046/j.1365-2133.1999.02912.x Occurrence Handle1:STN:280:DyaK1M3ot1aksw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  21. K Hatada M Kimura I Ono M Ozaki (1992) ArticleTitleDetermination of a new calcium antagonist and its main metabolite in plasma by thermospray liquid chromatography-mass spectrometry J Chromatogr 583 116–121 Occurrence Handle1484084 Occurrence Handle10.1016/0378-4347(92)80352-Q Occurrence Handle1:CAS:528:DyaK3sXhtl2isL0%3D

    Article  PubMed  CAS  Google Scholar 

  22. J Azuma I Yamamoto T Watase Y Orii T Tanigawa S Terashima K Yoshikawa T Tanaka K Kawano (1998) ArticleTitleEffects of grapefruit juice n the pharmacokinetics of the calcium channel blockers nifedipine and nisoldipine Curr Ther Res 59 619–633 Occurrence Handle10.1016/S0011-393X(98)85060-1 Occurrence Handle1:CAS:528:DyaK1cXms1ejsrg%3D

    Article  CAS  Google Scholar 

  23. S Shigetomi T Yokokawa S Fukuchi (1981) ArticleTitleA simple and rapid assay for the determination of plasma, urine and tissue catecholamine concentration by high-pressure liquid chromatography with fluorescent reaction Folia Endocrinol Jpn 57 950–958 Occurrence Handle1:CAS:528:DyaL3MXkvFehsro%3D

    CAS  Google Scholar 

  24. J Minami T Ishimitsu Y Kawano A Numabe H Matsuoka (1998) ArticleTitleComparison of 24-hour blood pressure, heart rate, and autonomic nerve activity in hypertensive patients treated with cilnidipine or nifedipine retard J Cardiovasc Pharmacol 32 331–336 Occurrence Handle9700998 Occurrence Handle10.1097/00005344-199808000-00023 Occurrence Handle1:CAS:528:DyaK1cXltVymtrc%3D

    Article  PubMed  CAS  Google Scholar 

  25. WH Cooke JB Hoag AA Crossman TA Kuusela KUO Tahvanainen DL Eckberg (1999) ArticleTitleHuman responses to upright tilt: a window on central autonomic integration J Physiol 517 617–628 Occurrence Handle10332107 Occurrence Handle10.1111/j.1469-7793.1999.0617t.x Occurrence Handle1:CAS:528:DyaK1MXktVykt7w%3D

    Article  PubMed  CAS  Google Scholar 

  26. InstitutionalAuthorNameTask Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996) ArticleTitleHeart rate variability. Standards of measurement, physiological interpretation, and clinical use Circulation 93 1043–1065

    Google Scholar 

  27. A Sugiyama Y Satoh A Takahara K Ando Y Nakamura K Hashimoto (2005) ArticleTitleComparison of the direct negative dromotropic effect of a new calcium channel blocker, cilnidipine, with that of nicardipine Heart Vessels 20 112–115 Occurrence Handle15912307 Occurrence Handle10.1007/s00380-004-0817-1

    Article  PubMed  Google Scholar 

  28. S Homma K Matsunami XY Han K Deguchi (2001) ArticleTitleHippocampus in relation to mental sweating response evoked by memory recall and mental calculation: a human electroencephalography study with dipole tracing Neurosci Lett 305 1–4 Occurrence Handle11356293 Occurrence Handle10.1016/S0304-3940(01)01759-1 Occurrence Handle1:CAS:528:DC%2BD3MXjsFeisb4%3D

    Article  PubMed  CAS  Google Scholar 

  29. T Okamoto S Iwase J Sugenoya T Mano Y Sugiyama K Yamamoto (1994) ArticleTitleDifferent thermal dependency of cutaneous sympathetic outflow to glabrous and hairy skin in humans Eur J Appl Physiol 68 460–4 Occurrence Handle1:STN:280:DyaK2M%2FksFClug%3D%3D

    CAS  Google Scholar 

  30. J Minami Y Kawano Y Makino H Matsuoka S Takishita (2000) ArticleTitleEffects of cilnidipine, a novel dihydropyridine calcium antagonist, on autonomic function, ambulatory blood pressure and heart rate in patients with essential hypertension Br J Clin Pharmacol 50 615–620 Occurrence Handle11136301 Occurrence Handle10.1046/j.1365-2125.2000.00299.x Occurrence Handle1:CAS:528:DC%2BD3MXkvV2jsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  31. JP Fauvel C Cerutti P Quelin M Laville MP Gustin CZ Paultre M Ducher (2000) ArticleTitleMental stress-induced increase in blood pressure is not related to baroreflex sensitivity in middle-aged healthy men Hypertension 35 887–891 Occurrence Handle10775556 Occurrence Handle1:STN:280:DC%2BD3c3ktVejsg%3D%3D

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Tsuyoshi Shiga, Yuichiro Yamada, Naoki Matsuda, Nobuhisa Hagiwara & Hiroshi Kasanuki

  2. Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan

    Takanori Tanaka & Akinori Urae

  3. Division for Evaluation and Analysis of Drug Information, Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan

    Masayuki Hashiguchi

Authors
  1. Tsuyoshi Shiga
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  2. Yuichiro Yamada
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  3. Naoki Matsuda
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  4. Takanori Tanaka
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  7. Nobuhisa Hagiwara
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Correspondence to Tsuyoshi Shiga.

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Shiga, T., Yamada, Y., Matsuda, N. et al. Influence of cilnidipine or nisoldipine on sympathetic activity in healthy male subjects. Heart Vessels 22, 404–409 (2007). https://doi.org/10.1007/s00380-007-0984-y

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  • DOI: https://doi.org/10.1007/s00380-007-0984-y

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