• 1
    Leenen FH. Clinical relevance of 24 h blood pressure control by 1,4-dihydropyridines. Am J Hypertens 1996;9:97S104S.
  • 2
    Freedman DD, Waters DD. ‘Second generation’ dihydropyridine calcium antagonists. Greater vascular selectivity and some unique applications. Drugs 1987;34:578598.
  • 3
    Lüscher TF, Cosentino F. The classification of calcium antagonists and their selection in the treatment of hypertension. A reappraisal. Drugs 1998;55:509517.
  • 4
    Lindqvist M, Kahan T, Melcher A, Ekholm M, Hjemdahl P. Long-term calcium antagonist treatment of human hypertension with mibefradil or amlodipine increases sympathetic nerve activity. J Hypertens 2007;25:169175.
  • 5
    Oike M, Inoue Y, Kitamura K, Kuriyama H. Dual action of FRC8653, a novel dihydropyridine derivative, on the Ba2+ current recorded from the rabbit basilar artery. Circ Res 1990;67:9931006.
  • 6
    Uneyama H, Takahara A, Dohmoto H, Yoshimoto R, Inoue K, Akaike N. Blockade of N-type Ca2+ current by cilnidipine (FRC-8653) in acutely dissociated rat sympathetic neurones. Br J Pharmacol 1997;122:3742.
  • 7
    Takahara A, Fujita S, Moki K, Ono Y, Koganei H, Iwayama S, Yamamoto H. Neuronal Ca2+ channel blocking action of an antihypertensive drug, cilnidipine, in IMR-32 human neuroblastoma cells. Hypertens Res 2003;26:743747.
  • 8
    Konda T, Takahara A, Maeda K, Dohmoto H, Yoshimoto R. Effects of a dual L/N-type Ca2+ channel blocker cilnidipine on neurally mediated chronotropic response in anesthetized dogs. Eur J Pharmacol 2001;413:117120.
  • 9
    Takahara A, Koganei H, Takeda T, Iwata S. Antisympathetic and hemodynamic property of a dual L/N-type Ca2+ channel blocker cilnidipine in rats. Eur J Pharmacol 2002;434:4347.
  • 10
    Sakata K, Shirotani M, Yoshida H, Nawada R, Obayashi K, Togi K, Miho N. Effects of amlodipine and cilnidipine on cardiac sympathetic nervous system and neurohormonal status in essential hypertension. Hypertension 1999;33:14471452.
  • 11
    Morimoto S, Takeda K, Oguni A, et al. Reduction of white coat effect by cilnidipine in essential hypertension. Am J Hypertens 2001;14:10531057.
  • 12
    Varadi G, Mori Y, Mikala G, Schwartz A. Molecular determinants of Ca2+ channel function and drug action. Trends Pharmacol Sci 1995;16:4349.
  • 13
    Tsien RW, Ellinor PT, Zhang JF, Bezprozvanny I. Molecular biology of calcium channels and structural determinants of key functions. J Cardiovasc Pharmacol 1996;27:S4S10.
  • 14
    Zhang JF, Randall AD, Horne WA, Sather WA, Tanabe T, Schwarz TL, Tsien RW. Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons. Neuropharmacology 1993;32:10751088.
  • 15
    Nowycky MC, Fox AP, Tsien RW. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature 1985;316:440443.
  • 16
    Fox AP, Nowycky MC, Tsien RW. Single-channel recordings of three types of calcium channels in chick sensory neurones. J Physiol 1987;394:173200.
  • 17
    Carbone E, Lux HD. A low voltage-activated, fully inactivating Ca2+ channel in vertebrate sensory neurones. Nature 1984;310:501502.
  • 18
    Tsien RW, Lipscombe D, Madison DV, Bley KR, Fox AP. Multiple types of neuronal calcium channels and their selective modulation. Trends Neurosci 1988;11:431438.
  • 19
    Bean BP. Classes of calcium channels in vertebrate cells. Annu Rev Physiol 1989;51:367384.
  • 20
    Tanabe T, Takeshima H, Mikami A, et al. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature 1987;328:313318.
  • 21
    Catterall WA, Striessnig J, Snutch TP, Perez-Reyes E. Voltage-gated calcium channels. In: CatterallWA, ChandyKG, GutmanGA, editors. The IUPHAR compendium of voltage-gated ion channels. Leads : IUPHAR Media, 2002:3156.
  • 22
    Hirning LD, Fox AP, McCleskey EW, Olivera BM, Thayer SA, Miller RJ, Tsien RW. Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons. Science 1988;239:5761.
  • 23
    Ishibashi H, Rhee JS, Akaike N. Regional defference of high voltage-activated Ca2+ channels in rat CNS neurones. NeuroReport 1995;6:16211624.
  • 24
    Dutar P, Rascol O, Lamour Y. ω-Conotoxin GVIA blocks synaptic transmission in the CA1 field of the hippocampus. Eur J Pharmacol 1989;174:261266.
  • 25
    Perez-Reyes E. Molecular physiology of low-voltage-activated T-type calcium channels. Physiol Rev 2003;83:117161.
  • 26
    Ono K, Iijima T. Ionic and molecular basis of cardiac automaticity in mammalian heart. In: MizukamiY, OhtsukaT, editors. Mol. Mechanisms of Heart Diseases. Trivandrum: Research SignPost, 2005, p. 122.
  • 27
    Tanaka H, Komikado C, Namekata I, et al. Species difference in the contribution of T-type calcium current to cardiac pacemaking as revealed by R(-)-efonidipine. J Pharmacol Sci 2008;107:99102.
  • 28
    Clasbrummel B, Osswald H, Illes P. Inhibition of noradrenaline release by omega-conotoxin GVIA in the rat tail artery. Br J Pharmacol 1989;96:101110.
  • 29
    Pruneau D, Angus JA. Omega-conotoxin GVIA is a potent inhibitor of sympathetic neurogenic responses in rat small mesenteric arteries. Br J Pharmacol 1990;100:180184.
  • 30
    McGuire D, Bowersox S, Fellmann JD, Luther RR. Sympatholysis after neuron-specific, N-type, voltage-sensitive calcium channel blockade: first demonstration of N-channel function in humans. J Cardiovasc Pharmacol 1997;30:400403.
  • 31
    Page IH. The mosaic theory of arterial hypertension–its interpretation. Perspect Biol Med 1967;10:325333.
  • 32
    Frohlich BD. The first Irvine H. Page lecture. The mosaic of hypertension: past, present and future. J Hypertens Suppl 1988;6:S211.
  • 33
    Frohlich ED. Mechanisms contributing to high blood pressure. Ann Intern Med 1983;98:709714.
  • 34
    Julius S, Schork N, Schork A. Sympathetic hyperactivity in early stages of hypertension: The Ann Arbor Data Set. J Cardiovasc Pharmacol 1988;12(Suppl. 3):S121S129.
  • 35
    Anderson EA, Sinkey CA, Lawton WJ, Mark AL. Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings. Hypertension 1989;14:177183.
  • 36
    Goldstein DS. Plasma catecholamines and essential hypertension. An analytical review. Hypertension 1983;5:8699.
  • 37
    Grassi G, Cattaneo BM, Seravalle G, Lanfranchi A, Mancia G. Baroreflex control of sympathetic nerve activity in essential and secondary hypertension. Hypertension 1998;31:6872.
  • 38
    Neumann J, Ligtenberg G, Oey L, Koomans HA, Blankestijn PJ. Moxonidine normalizes sympathetic hyperactivity in patients with eprosartan-treated chronic renal failure. J Am Soc Nephrol 2004;15:29022907.
  • 39
    Cohn JN, Levine B, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984;311:819823.
  • 40
    Julius S. Sympathetic hyperactivity and coronary risk in hypertension. Hypertension 1993;21:886893.
  • 41
    Spalding A, Vaitkevicius H, Dill S, MacKenzie S, Schmaier A, Lockette W. Mechanism of epinephrine-induced platelet aggregation. Hypertension 1998;31:603607.
  • 42
    Krespi PG, Makris TK, Hatzizacharias AN, et al. Moxonidine effect on microalbuminuria, thrombomodulin, and plasminogen activator inhibitor-1 levels in patients with essential hypertension. Cardiovasc Drugs Ther 1998;12:463467.
  • 43
    Campese VM, Kogosov E. Renal afferent denervation prevents hypertension in rats with chronic renal failure. Hypertension 1995;25:878882.
  • 44
    Campese VM, Kogosov E, Koss M. Renal afferent denervation prevents the progression of renal disease in the renal ablation model of chronic renal failure in the rat. Am J Kidney Dis 1995;26:861865.
  • 45
    Ye S, Zhong H, Yanamadala V, Campese VM. Renal injury caused by intrarenal injection of phenol increases afferent and efferent renal sympathetic nerve activity. Am J Hypertens 2002;15:717724.
  • 46
    Takizawa S, Matsushima K, Fujita H, Nanri K, Ogawa S, Shinohara Y. A selective N-type calcium channel antagonist reduces extracellular glutamate release and infarct volume in focal cerebral ischemia. J Cereb Blood Flow Metab 1995;15:611618.
  • 47
    Uneyama H, Uchida H, Konda T, Yoshimoto R, Akaike N. Selectivity of dihydropyridines for cardiac L-type and sympathetic N-type Ca2+ channels. Eur J Pharmacol 1999;373:93100.
  • 48
    Fleckenstein A. History of calcium antagonists. Circ Res 1983;52(Suppl. I):316.
  • 49
    Opie LH, Buhler FR, Fleckenstein A, Harrison DC, Poole-Wilson PA, Schwartz A, Vanhoutte PM. International Society and Federation of Cardiology: Working Group on classification of calcium antagonists for cardiovascular disease. Am J Cardiol 1987;60:630632.
  • 50
    Singh BN. The mechanism of action of calcium antagonists relative to their clinical applications. Br J Clin Pharmacol 1986;21:109S121S.
  • 51
    Spedding M, Paoletti R. III. Classification of calcium channels and the sites of action of drugs modifying channel function. Pharmacol Rev 1992;44:363376.
  • 52
    Spedding M. Calcium antagonist subgroups. Trends Pharmacol Sci 1985;5:109114.
  • 53
    Toyo-oka T, Nayler WG. Third generation calcium entry blockers. Blood Press 1996;5:206208.
  • 54
    Takahara A, Iwasaki H, Nakamura Y, Sugiyama A. Cardiac effects of L/N-type Ca2+ channel blocker cilnidipine in anesthetized dogs. Eur J Pharmacol 2007;565:166170.
  • 55
    Nap A, Mathy M-J, Balt JC, Pfaffendorf M, Van Zwieten PA. The evaluation of the N-type channel blocking properties of cilnidipine and other voltage-dependent calcium antagonists. Fundam Clin Pharmacol 2004;18:309319.
  • 56
    Uneyama H, Uchida H, Yoshimoto R, Ueno S, Inoue K, Akaike N. Effects of a novel antihypertensive drug, cilnidipine, on catecholamine secretion from differentiated PC12 cells. Hypertension 1998;31:11951199.
  • 57
    Hosono M. Changes in heart rate and plasma norepinephrine level of conscious spontaneously hypertensive rats treated with cilnidipine (FRC-8653). Jpn Pharmacol Ther 1995;23:159170.
  • 58
    Karasawa A, Nomura H, Nito M, et al. Effects of benidipine hydrochloride (Coniel) on blood pressure, heart rate and plasma norepinephrine concentration in spontaneously hypertensive rats. Nippon Yakurigaku Zasshi 1999;113:317326.
  • 59
    Yasuma K. Evaluation of Sympathetic Presynaptic in Humans. J Juzen Med Soc 1999;108:200212.
  • 60
    Ferguson DW, Hayes DW. Nifedipine potentiates cardiopulmonary baroreflex control of sympathetic nerve activity in healthy humans. Direct evidence from microneurographic studies. Circulation 1989;80:285298.
  • 61
    Wolk R, Kulakowski P, Ceremuzynski L. Nifedipine and captopril exert divergent effects on heart rate variability in patients with acute episodes of hypertension. J Hum Hypertens 1996;10:327332.
  • 62
    Shinagawa M, Kubo Y, Otsuka K, Ohkawa S, Cornélissen G, Halberg F. Impact of circadian amplitude and chronotherapy: relevance to prevention and treatment of stroke. Biomed Pharmacother 2001;55:125s132s.
  • 63
    Binggeli C, Corti R, Sudano I, Luscher TF, Noll G. Effects of chronic calcium channel blockade on sympathetic nerve activity in hypertension. Hypertension 2002;39:892896.
  • 64
    Ruzicka M, Coletta E, Floras  , Leenen FH. Effects of low-dose nifedipine GITS on sympathetic activity in young and older patients with hypertension. J Hypertens 2004;22:10391044.
  • 65
    Minami J, Numabe A, Andoh N, Kobayashi N, Horinaka S, Ishimitsu T, Matsuoka H. Comparison of once-daily nifedipine controlled-release with twice-daily nifedipine retard in the treatment of essential hypertension. Br J Clin Pharmacol 2004;57:632639.
  • 66
    Wenzel RR, Allegranza G, Binggeli C, Shaw S, Weidmann P, Lüscher TF, Noll G. Differential activation of cardiac and peripheral sympathetic nervous system by nifedipine: Role of pharmacokinetics. J Am Coll Cardiol 1997;29:16071614.
  • 67
    Okabayashi J, Matsubayashi K, Sato T, Ozawa T. Effect of nifedipine and enalapril on cardiac autonomic activity in elderly hypertensive patients. Nippon Ronen Igakkai Zasshi 1994;31:285292.
  • 68
    Minami J, Ishimitsu T, Kawano Y, Numabe A, Matsuoka H. Comparison of 24-hour blood pressure, heart rate, and autonomic nerve activity in hypertensive patients treated with cilnidipine or nifedipine retard. J Cardiovasc Pharmacol 1998;32:331336.
  • 69
    Minami J, Ishimitsu T, Kawano Y, Matsuoka H. Effects of amlodipine and nifedipine retard on autonomic nerve activity in hypertensive patients. Clin Exp Pharmacol Physiol 1998;25:572576.
  • 70
    Scholz H. Pharmacological aspects of calcium channel blockers. Cardiovasc Drugs Ther 1997;10:869872.
  • 71
    Nomura M, Nakaya Y, Uemura E, et al. Effects of benidipine hydrochloride on autonomic nervous activity in hypertensive patients with high- and low-salt diets. Arzneim-Forsch/Drug Res 2003;53:314320.
  • 72
    Hoshide S, Kario K, Mitushashi T, Ikeda U, Shimada K. Is there any difference between intermediate-acting and long-acting calcium antagonists in diurnal blood pressure and autonomic nervous activity in hypertensive coronary artery disease patients? Hypertens Res 2000;23:714.
  • 73
    Muneta S, Kohara K, Hiwada K. Effects of benidipine hydrochloride on 24-hour blood pressure and blood pressure response to mental stress in elderly patients with essential hypertension. Int J Clin Pharmacol Ther 1999;37:141147.
  • 74
    Maier-Lenz H, Rode H, Lenau H, et al. Benidipine hydrochloride – a new calcium-channel blocker of the dihydropyridine type. Pharmacokinetics, pharmacodynamics, tolerance and dose finding in mild to moderate hypertension. Arzneimittelforschung 1988;38:17571763.
  • 75
    Yun HY, Yun MH, Kang W, Kwon KI. Pharmacokinetics and pharmacodynamics of benidipine using a slow receptor-binding model. J Clin Pharm Ther 2005;30:541547.
  • 76
    Harada K, Nomura M, Nishikado A, Uehara K, Nakaya Y, Ito S. Clinical efficacy of efonidipine hydrochloride, a T-type calcium channel inhibitor, on sympathetic activities – Examination using spectral analysis of heart rate/blood pressure variabilities and 123I-metaiodobenzylguanidine myocardial scintigraphy. Circ J 2003;67:139145.
  • 77
    Saito T, Fujii K, Takizawa T, et al. Effects of the new calcium antagonist efonidipine hydrochloride on resting and exercise hemodynamics in patients with stable effort angina. Arzneim-Forsch/Drug Res 1996;46:861867.
  • 78
    Faulkner JK, McGibney D, Chasseaud LF, Perry JL, Taylor IW. The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily. Br J Clin Pharmacol 1986;22:2125.
  • 79
    Koike H, Kimura T, Kawasaki T, Sada T, Ikeda T, Sanbuissho A, Saito H. Azelnidipine, long-acting calcium channel blocker with slow onset and high vascular affinity. Annu Rep Sankyo Res Lab 2002, 54, 164.
  • 80
    Struck J, Muck P, Trübger D, Handrock R, Weidinger G, Dendorfer A, Dodt C. Effects of selective angiotensin II blockade on sympathetic nerve activity in primary hypertensive subjects. J Hypertens 2002;20:11431149.
  • 81
    Ligtenberg G, Blankestijn PJ, Oey PL, et al. Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure. N Engl J Med 1999;340:13211328.
  • 82
    Yasuda G, Ando D, Hirawa N, Umemura S, Tochikubo O. Effects of losartan and amlodipine on urinary albumin excretion and ambulatory blood pressure in hypertensive type 2 diabetic patients with overt nephropathy. Diabetes Care 2005;28:18621868.
  • 83
    Karas M, Lacourcière Y, LeBlanc AR, et al. Effect of the renin – angiotensin system or calcium channel blockade on the circadian variation of heart rate variability, blood pressure and circulating catecholamines in hypertensive patients. J Hypertens 2005;23:12511260.
  • 84
    Lefrandt JD, Heitmann J, Sevre K, et al. The effects of dihydropyridine and phenylalkylamine calcium antagonist classes on autonomic function in hypertension: The VAMPHYRE Study. Am J Hypertens 2001;14:10831089.
  • 85
    De Champlain J, Karas M, Assouline L, Nadeau R, LeBlanc AR, Dubé B, Larochelle P. Effects of valsartan or amlodipine alone or in combination on plasma catecholamine levels at rest and during standing in hypertensive patients. J Clin Hypertens 2007;9:168178.
  • 86
    Arita M, Hashizume T, Tanigawa K, Yamamoto H, Nishio I. A new Ca-antagonist, azelnidipine, reduced blood pressure during exercise without augmentation of sympathetic nervous system in essential hypertension: a randomized, double-blind, placebo-controlled trial. J Cardiovasc Pharmacol 1999;33:186192.
  • 87
    Eguchi K, Tomizawa H, Ishikawa J, et al. Effects of new calcium channel blocker, azelnidipine, and amlodipine on baroreflex sensitivity and ambulatory blood pressure. J Cardiovasc Pharmacol 2007;49:394400.
  • 88
    Nakamura T, Sugaya T, Kawagoe Y, et al. Azelnidipine reduces urinary protein excretion and urinary liver-type fatty acid binding protein in patients with hypertensive chronic kidney disease. Am J Med Sci 2007;333:321326.
  • 89
    Yamagashi T. Efficacy of azelnidipine on home blood pressure and pulse rate in patients with essential hypertension: comparison with amlodipine. Hypertens Res 2006;29:767773.
  • 90
    Sada T. Pharmacological profiles and clinical effects of azelnidipine, a long-acting calcium channel blocker. Nippon Yakurigaku Zasshi 2003;122:539547.
  • 91
    Kuramoto K, Ichikawa S, Hirai A, Kanada S, Nakachi T, Ogihara T. Azelnidipine and amlodipine: A comparison of their pharmacokinetics and effects on ambulatory blood pressure. Hypertens Res 2003;26:201208.
  • 92
    Yamamoto E, Lai ZF, Yamashita T, et al. Enhancement of cardiac oxidative stress by tachycardia and its critical role in cardiac hypertrophy and fibrosis. J Hypertens 2006;24:20572069.
  • 93
    Kimura Y, Hirooka Y, Sagara Y, Sunagawa K. Long-acting calcium channel blocker, azelnidipine, increases endothelial nitric oxide synthase in the brain and inhibits sympathetic nerve activity. Clin Exp Hypertens 2007;29:1321.
  • 94
    Shokoji T, Fujisawa Y, Kiyomoto H, et al. Effects of a new calcium channel blocker, azelnidipine, on systemic hemodynamics and renal sympathetic nerve activity in spontaneously hypertensive rats. Hypertens Res 2005;28:10171023.
  • 95
    Hosono M, Fujii S, Hiruma T, et al. Inhibitory effect of cilnidipine on vascular sympathetic neurotransmission and subsequent vasoconstriction in spontaneously hypertensive rats. Jpn J Pharmacol 1995;69:127134.
  • 96
    Takahara A, Dohmoto H, Hisa H, Satoh S, Yoshimoto R. Cilnidipine attenuates renal nerve stimulation-induced renal vasoconstriction and antinatriuresis in anesthetized dogs. Jpn J Pharmacol 1997;75:2732.
  • 97
    Nagayama T, Yoshida M, Suzukikusaba M, Hisa H, Kimura T, Satoh S. Effect of cilnidipine, a novel dihydropyridine Ca2+ channel blocker, on adrenal catecholamine secretion in anesthetized dogs. J Cardiovasc Pharmacol 1998;32:479484.
  • 98
    Takeda S, Ueshiba H, Hattori Y, Irie M. Cilnidipine, the N- and L-type calcium channel antagonist, reduced on 24-h urinary catecholamines and C-peptide in hypertensive non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1999;44:197205.
  • 99
    Ito K, Sugihara H, Nishikawa S, Adachi Y, Kato S, Azuma A, Matsubara H. Clinical usefulness of a dual L/N-type Ca2+ channel blocker, cilnidipine, in patients with chronic heart failure: Assessment with 123I-MIBG myocardial scintigraphy. Kaku Igaku 2003;40:421430.
  • 100
    Sakata K, Yoshida H, Tamekiyo H, Obayashi K, Nawada R, Doi O, Mori N. Comparative effect of cilnidipine and quinapril on left ventricular mass in mild essential hypertension. Drugs Exp Clin Res 2003;XXIX:117123.
  • 101
    Minami J, Kawano Y, Makino Y, Matsuoka H, Takishita S. Effects 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 2000;50:615620.
  • 102
    Kitahara Y, Saito F, Akao M, et al. Effect of morning and bedtime dosing with cilnidipine on blood pressure, heart rate, and sympathetic nervous activity in essential hypertensive patients. J Cardiovasc Pharmacol 2004;43:6873.
  • 103
    Nagahama S, Norimatsu T, Maki T, Yasuda M, Tanaka S. The effect of combination therapy with an L/N-Type Ca2+ channel blocker, cilnidipine, and an angiotensin II receptor blocker on the blood pressure and heart rate in Japanese hypertensive patients: an observational study conducted in Japan. Hypertens Res 2007;30:815822.
  • 104
    Hoshide S, Kario K, Ishikawa J, Eguchi K, Shimada K. Comparison of the effects of cilnidipine and amlodipine on ambulatory blood pressure. Hypertens Res 2005;28:10031008.
  • 105
    Taira N. Differences in cardiovascular profile among calcium antagonists. Am J Cardiol 1987;30;59:24B29B.
  • 106
    Ikeda K, Hosino M, Iida H, Ohnishi H. Antihypertensive and cardiovascular profiles of newly synthesized dihydropyridine derivative 2-methoxyethyl (E)-3-phenyl-2-propen-1-yl (+/-)-1,4-dihydro-2,6-dimethyl- 4-(3- nitrophenyl)pyridine-3,5-dicarboxylate (FRC-8653). Pharmacometrics 1992;44:433442.
  • 107
    Sugiyama A, Satoh Y, Takahara A, Ando K, Nakamura Y, Hashimoto K. Comparison of the direct negative dromotropic effect of a new calcium channel blocker, cilnidipine, with that of nicardipine. Heart Vessels 2005;20:112115.
  • 108
    Ishii M, Matsuoka H, Iimura O, et al. Efficacy and safety of FRC-8653 (cilnidipine) in the long-term treatment of patients with essential hypertension. Jpn Pharmacol Ther 1993;21:S123-S153.
  • 109
    Iimura O, Ishii M, Inagaki Y, et al. Clinical study of FRC-8653 (cilnidipine) in patients with severe hypertension. Jpn Pharmacol Ther 1993;21:S155-S170.
  • 110
    Ashizawa N, Seto S, Shibata Y, Yano K. Bedtime administration of cilnidipine controls morning hypertension. Int Heart J 2007;48:597603.
  • 111
    Yamagishi T. Beneficial effect of cilnidipine on morning hypertension and white-coat effect in patients with essential hypertension. Hypertens Res 2006;29:339344.
  • 112
    Nagai H, Minatoguchi S, Chen X-H, et al. Cilnidipine, an N+L-type dihydropyridine Ca channel blocker, suppresses the occurrence of ischemia/reperfusion arrhythmia in a rabbit model of myocardial infarction. Hypertens Res 2005;28:361368.
  • 113
    Takahara A, Sugiyama A, Hashimoto K. Long-term blockade of N-type Ca2+ channels reversed the ventricular electrical remodeling in the canine model of long QT syndrome. Circ J 2006;70(Suppl I):575. (Abstract)
  • 114
    Saitoh M, Sugiyama A, Nakamura Y, Hashimoto K. Antianginal effects of L-type and N-type calcium channel blocker cilnidipine assessed using the vasopressin-induced experimental angina model of rats. J Pharmacol Sci 2003;91(Suppl I):152P. (Abstract)
  • 115
    Chung WJ, Oh PC, Ahn TH, et al. Effects of cilnidipine versus atenolol on left ventricular diastolic function and hypertrophy in essential hypertension-CANDLE trial. J Hypertens 2008;26(Suppl I):459.
  • 116
    Tan H-W, Li L, Zhang W, Ma ZY, Zhong XZ, Zhang Y. Effect of cilnidipine on left ventricular function in hypertensive patients as assessed by tissue Doppler Tei index. J Human Hypertens 2006;20:618624.
  • 117
    Ma ZY, Li L, Zhong XZ, et al. Cilnidipine improves left-ventricular midwall function independently of blood pressure changes in Chinese patients with hypertension. J Cardiovasc Pharmacol 2007;49:3338.
  • 118
    Strandgaard S, Olesen J, Skinhøj E, Lassen NA. Autoregulation of brain circulation in severe arterial hypertension. Br Med J 1973;1:507510.
  • 119
    Watanabe K, Dozen M, Hayashi Y. Effect of cilnidipine(FRC-8653) on autoregulation of cerebral blood flow. Nippon Yakurigaku Zasshi 1995;106:393399.
  • 120
    Murai Y, Uneyama H, Ishibashi H, Takahama K, Akaike N. Preferential inhibition of L- and N-type calcium channels in the rat hippocampal neurons by cilnidipine. Brain Res 2000;854:610.
  • 121
    Takahara A, Konda T, Enomoto A, Kondo N. Neuroprotective effects of a dual L/N-type Ca2+ channel blocker cilnidipine in the rat focal brain ischemia model. Biol Pharm Bull 2004;27:13881391.
  • 122
    Tomiyama H, Kimura Y, Kuwabara Y, et al. Cilnidipine more highly attenuates cold pressor stress-induced platelet activation in hypertension than does amlodipine. Hypertens Res 2001;24:679684.
  • 123
    Hayashi K, Wakino S, Sugano N, Ozawa Y, Homma K, Saruta T. Ca2+ channel subtypes and pharmacology in the kidney. Circ Res 2007;100:342353.
  • 124
    Kon V. Neural control of renal circulation. Miner Electrolyte Metab 1989;15:3343.
  • 125
    Fujii S, Okazaki Y, Yatabe J, Hosono M. Potent vasodilative action of cilnidipine on glomerular arterioles in rat hydronehrotic kidney. Jpn Pharmacol Ther 1999;27:163167.
  • 126
    Konda T, Enomoto A, Takahara A, Yamamoto H. Effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal injuries in Dahl salt-sensitive rats. Biol Pharm Bull 2006;29:933937.
  • 127
    Konda T, Enomoto A, Matsushita J, Takahara A, Moriyama T. The N- and L-type calcium channel blocker cilnidipine suppresses renal injury in Dahl rats fed a high-sucrose diet, an experimental model of metabolic syndrome. Nephron Physiol 2005;101:113.
  • 128
    Zhou X, Ono H, Ono Y, Frolich ED. N- and L-type calcium channel antagonist improves glomerular dynamics, reverses severe nephrosclerosis, and inhibits apoptosis and proliferation in an L-NAME/SHR model. J Hypertens 2002;20:9931000.
  • 129
    Rose GW, Ikebukuro H, Ikebukuro H. Cilnidipine is as effective as benazepril for control of blood pressure and proteinuria in hypertensive patients with benign nephrosclerosis. Hypertens Res 2001;24:377383.
  • 130
    Kojima S, Shida M, Yokoyama H. Comparison between cilnidipine and amlodipine besilate with respect to proteinuria in hypertensive patients with renal diseases. Hypertens Res 2004;27:379385.
  • 131
    Tsuchihashi T, Ueno M, Tominaga M, Kajioka T, Onaka U, Eto K, Goto K. Anti-proteinuric effect of an N-type calcium channel blocker, cilnidipine. Clin Exp Hypertens 2005;27:583591.
  • 132
    Katayama K, Nomura S, Ishikawa H, Murata T, Koyabu S, Nakano T. Comparison between valsartan and valsartan plus cilnidipine in type II diabetics with normo- and microalbuminuria. Kidney Int 2006;70:151156.
  • 133
    Fujita T, Ando K, Nishimura H, Ideura T, Yasuda G, Isshiki M, Takahashi K. For Cilnidipine versus Amlodipine Randomised Trial for Evaluation in Renal Disease (CARTER) Study Investigators. Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease. Kidney Int 2007;72:15431549.
  • 134
    Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:12961305.
  • 135
    Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004;164:659663.
  • 136
    Irie F, Iso H, Sairenchi T, et al. The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population. Kidney Int 2006;69:12641271.
  • 137
    Grassi G, Dell'Oro R, Facchini A, Quarti Trevano F, Bolla GB, Mancia G. Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives. J Hypertens 2004;22:23632369.
  • 138
    Masuo K, Mikami H, Itoh M, Ogihara T, Tuck ML. Sympathetic activity and body mass index contribute to blood pressure levels. Hypertens Res 2000;23:303310.
  • 139
    Ramanadham S, Turk J. ω-Conotoxin inhibits glucose- and arachidonic acid-induced rises in intracellular [Ca2+] in rat pancreatic islet beta-cells. Cell Calcium 1994;15:259264.
  • 140
    Komatsu M, Yokokawa N, Takeda T, Nagasawa Y, Aizawa T, Yamada T. Pharmacological characterization of the voltage-dependent calcium channel of pancreatic B-cell. Endocrinology 1989;125:20082014.
  • 141
    Gromada J, Bokvist K, Ding WG, Barg S, Buschard K, Renström E, Rorsman P. Adrenaline stimulates glucagon secretion in pancreatic A-cells by increasing the Ca2+ current and the number of granules close to the L-type Ca2+ channels. J Gen Physiol 1997;110:217228.
  • 142
    Barg S, Galvanovskis J, Göpel SO, Rorsman P, Eliasson L. Tight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells. Diabetes 2000;49:15001510.
  • 143
    Takahashi E, Ito M, Miyamoto N, Nagasu T, Ino M, Tanaka I. Increased glucose tolerance in N-type Ca2+ channel α1B-subunit gene-deficient mice. Int J Mol Med 2005;15:937944.
  • 144
    Takada M, Ura N, Higashiura K, Murakami H, Togashi N, Shimamoto K. Effects of cilnidipine on muscle fiber composition, capillary density and muscle blood flow in fructose-fed rats. Hypertens Res 2001;24:565572.
  • 145
    Takeda S, Ueshiba H, Hattori Y, Irie M. Cilnidipine, the N- and L-type calcium channel antagonist, reduced on 24-h urinary catecholamines and C-peptide in hypertensive non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1999;44:197205.
  • 146
    Ueshiba H, Miyachi Y. Effects ofCilnidipine on Adrenocortical Steroid Hormones and Insulin Resistance in Hypertensive Patients with Obesity. Ther Res 2002;23:24932497.