Skip to main content
SpringerLink
Log in

The N-type and L-type calcium channel blocker cilnidipine suppresses renal injury in Dahl rats fed a high-salt diet

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

The aims of the present study were to compare the effects of cilnidipine [L-type/N-type calcium channel blocker (CCB)] and amlodipine (L-type CCB) alone or in combination with the angiotensin II receptor blocker (ARB), valsartan, on blood pressure (BP), kidney function in Dahl salt-sensitive (DS) rats. DS rats fed a high-salt diet were divided into six groups; control (n = 13), two CCB (cilnidipine or amlodipine) groups at 1 mg/kg/day (n = 10), ARB (valsartan) at 10 mg/kg/day (n = 12), cilnidipine + valsartan (CV, n = 12), and amlodipine + valsartan (AV, n = 12). BPs were lower in the combination therapy groups than in those given either drug alone, but only CV inhibited the increase in urinary albumin excretion (UAE) and lowered the glomerular sclerosis score. In addition, AV elevated plasma renin activity and the angiotensin II concentration, and thus failed to inhibit increases in UAE and to lower glomerular sclerosis score. In conclusion, combination therapy with CCB and ARB decreases BP more effectively than either drug alone. When used in combination with valsartan, cilnidipine is more effective than amlodipine for preventing kidney injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Japanese Society of Hypertension (2006) Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). Hypertens Res 29(Suppl):S1–S105

    Article  Google Scholar 

  2. Gradman AH (2004) Managing high-risk patients with hypertension: focus on the renin-angiotensin system. J Clin Hypertens (Greenwich) 6:501–508

    Article  CAS  Google Scholar 

  3. Cushman WC, Ford CE, Einhorn PT, Wright JT Jr, Preston RA, Davis BR, Basile JN, Whelton PK, Weiss RJ, Bastien A, Courtney DL, Hamilton BP, Kirchner K, Louis GT, Retta TM, Vidt DG, ALLHAT Collaborative Research Group (2008) Blood pressure control by drug group in the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich) 10:751–760

    Article  CAS  Google Scholar 

  4. Konda T, Enomoto A, Matsushita J, Takahara A, Moriyama T (2005) 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 101:1–13

    Article  Google Scholar 

  5. Omae K, Ogawa T, Nitta K (2009) Influence of T-calcium channel blocker treatment on deterioration of renal function in chronic kidney disease. Heart Vessels 24:301–307

    Article  PubMed  Google Scholar 

  6. Takahara A, Koganei H, Takeda T, Iwata S (2002) Antisympathetic and hemodynamic property of a dual L/N-type Ca(2+) channel blocker cilnidipine in rats. Eur J Pharmacol 434:43–47

    Article  CAS  PubMed  Google Scholar 

  7. Shiga T, Yamada Y, Matsuda N, Tanaka T, Urae A, Hashiguchi M, Hagiwara N, Kasanuki H (2007) Influence of cilnidipine or nisoldipine on sympathetic activity in healthy male subjects. Heart Vessels 22:404–409

    Article  PubMed  Google Scholar 

  8. Nagahama S, Norimatsu T, Maki T, Yasuda M, Tanaka S (2007) The effect of combination therapy with an L/N-Type Ca(2+) 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 30:815–822

    Article  CAS  PubMed  Google Scholar 

  9. Varagic J, Susic D, Frohlich ED (2002) Cilnidipine improves spontaneously hypertensive rat coronary hemodynamics without altering cardiovascular mass and collagen. J Hypertens 20:317–322

    Article  CAS  PubMed  Google Scholar 

  10. Sakata K, Yoshida H, Tamekiyo H, Obayashi K, Nawada R, Doi O, Mori N (2003) Comparative effect of cilnidipine and quinapril on left ventricular mass in mild essential hypertension. Drugs Exp Clin Res 29:117–123

    CAS  PubMed  Google Scholar 

  11. Takemori K, Ishida H, Dote K, Yamamoto K, Ito H (2005) Prophylactic effects of an N- and L-type Ca2+ antagonist, cilnidipine, against cardiac hypertrophy and dysfunction in stroke-prone, spontaneously hypertensive rats. Can J Physiol Pharmacol 83:785–790

    Article  CAS  PubMed  Google Scholar 

  12. Nagai H, Minatoguchi S, Chen XH, Wang N, Arai M, Uno Y, Lu C, Misao Y, Onogi H, Kobayashi H, Takemura G, Maruyama R, Fujiwara T, Fujiwara H (2005) 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 28:361–368

    Article  CAS  PubMed  Google Scholar 

  13. Tsuchihashi T, Ueno M, Tominaga M, Kajioka T, Onaka U, Eto K, Goto K (2005) Anti-proteinuric effect of an N-type calcium channel blocker, cilnidipine. Clin Exp Hypertens 27:583–591

    Article  CAS  PubMed  Google Scholar 

  14. Kojima S, Shida M, Yokoyama H (2004) Comparison between cilnidipine and amlodipine besilate with respect to proteinuria in hypertensive patients with renal diseases. Hypertens Res 27:379–385

    Article  CAS  PubMed  Google Scholar 

  15. Rose GW, Kanno Y, Ikebukuro H, Kaneko M, Kaneko K, Kanno T, Ishida Y, Suzuki H (2001) Cilnidipine is as effective as benazepril for control of blood pressure and proteinuria in hypertensive patients with benign nephrosclerosis. Hypertens Res 24:377–383

    Article  CAS  PubMed  Google Scholar 

  16. Fujita T, Ando K, Nishimura H, Ideura T, Yasuda G, Isshiki M, Takahashi K, Cilnidipine versus Amlodipine Randomised Trial for Evaluation in Renal Disease (CARTER) Study Investigators (2007) Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease. Kidney Int 72:1543–1549

    Article  CAS  PubMed  Google Scholar 

  17. Yagi S, Goto S, Yamamoto T, Kurihara S, Katayama S (2003) Effect of cilnidipine on insulin sensitivity in patients with essential hypertension. Hypertens Res 26:383–387

    Google Scholar 

  18. Yao K, Sato H, Ina Y, Suzuki K, Ohno T, Shirakura S (2003) Renoprotective effects of benidipine in combination with angiotensin II type 1 receptor blocker in hypertensive Dahl rats. Hypertens Res 26:635–641

    Article  CAS  PubMed  Google Scholar 

  19. Lopez LM, Thorman AD, Mehta JL (1990) Effects of amlodipine on blood pressure, heart rate, catecholamines, lipids and responses to adrenergic stimulus. Am J Cardiol 66:1269–1271

    Article  CAS  PubMed  Google Scholar 

  20. Phillips JK (2005) Pathogenesis of hypertension in renal failure: role of the sympathetic nervous system and renal afferents. Clin Exp Pharmacol Physiol 32:415–418

    Article  CAS  PubMed  Google Scholar 

  21. Tuncel M, Augustyniak R, Zhang W, Toto RD, Victor RG (2002) Sympathetic nervous system function in renal hypertension. Curr Hypertens Rep 4:229–236

    Article  PubMed  Google Scholar 

  22. Eguchi K, Kario K, Shimada K (2002) Differential effects of a long-acting angiotensin converting enzyme inhibitor (temocapril) and a long-acting calcium antagonist (amlodipine) on ventricular ectopic beats in older hypertensive patients. Hypertens Res 25:329–333

    Article  CAS  PubMed  Google Scholar 

  23. Hosono M, Hiruma T, Watanabe K, Hayashi Y, Ohnishi H, Takata Y, Kato H (1995) Inhibitory effect of cilnidipine on pressor response to acute cold stress in spontaneously hypertensive rats. Jpn J Pharmacol 69:119–125

    Article  CAS  PubMed  Google Scholar 

  24. Konda T, Enomoto A, Takahara A, Yamamoto H (2006) Effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal injuries in Dahl salt-sensitive rats. Biol Pharm Bull 29:933–937

    Article  CAS  PubMed  Google Scholar 

  25. Minami J, Kawano Y, Makino Y, Matsuoka H, Takishita S (2000) 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 50:615–620

    Article  CAS  PubMed  Google Scholar 

  26. Hoshide S, Kario K, Ishikawa J, Eguchi K, Shimada K (2005) Comparison of the effects of cilnidipine and amlodipine on ambulatory blood pressure. Hypertens Res 28:1003–1008

    Article  CAS  PubMed  Google Scholar 

  27. de Champlain J, Karas M, Assouline L, Nadeau R, LeBlanc AR, Dube B, Larochelle P (2007) Effects of valsartan or amlodipine alone or in combination on plasma catecholamine levels at rest and during standing in hypertensive patients. J Clin Hypertens (Greenwich) 9:168–178

    Article  Google Scholar 

  28. Seymour EM, Parikh RV, Singer AA, Bolling SF (2006) Moderate calorie restriction improves cardiac remodeling and diastolic dysfunction in the Dahl-SS rat. J Mol Cell Cardiol 41:661–668

    Article  CAS  PubMed  Google Scholar 

  29. Libera LD, Vescovo G (2004) Muscle wastage in chronic heart failure, between apoptosis, catabolism and altered anabolism: a chimaeric view of inflammation? Curr Opin Clin Nutr Metab Care 7:435–441

    Article  PubMed  Google Scholar 

  30. Elmarakby AA, Quigley JE, Pollock DM, Imig JD (2006) Tumor necrosis factor alpha blockade increases renal Cyp2c23 expression and slows the progression of renal damage in salt-sensitive hypertension. Hypertension 47:557–562

    Article  CAS  PubMed  Google Scholar 

  31. Russell ST, Wyke SM, Tisdale MJ (2006) Mechanism of induction of muscle protein degradation by angiotensin II. Cell Signal 18(7):1087–1096

    Google Scholar 

Download references

Acknowledgments

All authors contributed to the concept and study design, manuscript writing and editing, and final approval. This work was supported by Ajinomoto Co., Inc.

Author information

Authors and Affiliations

  1. Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, 210-8681, Japan

    Shizuka Aritomi, Hajime Koganei, Hirotaka Wagatsuma, Akira Mitsui & Tomoyuki Konda

  2. Department of Medicine, Kidney Center, Tokyo Women’s Medical University, Tokyo, Japan

    Tetsuya Ogawa & Kosaku Nitta

Authors
  1. Shizuka Aritomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hajime Koganei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hirotaka Wagatsuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akira Mitsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tetsuya Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kosaku Nitta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tomoyuki Konda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shizuka Aritomi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aritomi, S., Koganei, H., Wagatsuma, H. et al. The N-type and L-type calcium channel blocker cilnidipine suppresses renal injury in Dahl rats fed a high-salt diet. Heart Vessels 25, 549–555 (2010). https://doi.org/10.1007/s00380-010-0005-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-010-0005-4

Keywords

Search

Navigation