Benidipine Attenuates Glomerular Hypertension and Reduces Albuminuria in Patients with Metabolic Syndrome

Article metrics

Abstract

Recent studies have shown that metabolic syndrome is associated with an increased risk for chronic kidney disease. We recently found that the prevalence of sodium-sensitive hypertension in patients with metabolic syndrome was significantly higher than that in patients with essential hypertension but without metabolic syndrome. We therefore assessed the effects of benidipine, a long-acting calcium channel blocker, on the sodium sensitivity of blood pressure and renal hemodymamics in 5 patients with metabolic syndrome. Glomerular hemodynamics were assessed using pressure-natriuresis curves, which were constructed by plotting the urinary excretion of sodium as a function of the mean arterial pressure, which was calculated as the mean of 48 values based on 24-h monitoring, during the intake of low (3 g NaCl daily) and relatively high (10 g NaCl daily) sodium diets. Under the relatively high sodium diet condition, benidipine significantly lowered systolic and diastolic blood pressure. The pressure-natriuresis curve was steeper after the administration of benidipine. Benidipine lowered glomerular capillary hydraulic pressure (PGC) levels (from 54.4±7.5 to 47.0±7.0 mmHg, p=0.0152) and reduced both the resistance of the afferent arterioles (from 10,338±2,618 to 9,026±2,627 dyn·s/cm5, p=0.047) and the resistance of the efferent arterioles (from 4,649±2,039 to 2,419±2,081 dyn·s/cm5, p=0.003). The urinary albumin excretion rate also decreased after the administration of benidipine. These findings indicated that benidipine may be effective for reducing the risk of developing chronic kidney disease in patients with metabolic syndrome.

References

  1. 1

    Isomaa B, Almgren P, Tuomi T, et al: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001; 24: 683–689.

  2. 2

    Kahn R, Buse J, Ferrannini E, Stern M : The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2005; 28: 2289–2304.

  3. 3

    Chen J, Muntner P, Hamm LL, et al: The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med 2004; 140: 167–174.

  4. 4

    Uzu T, Kimura G, Yamauchi A, et al: Enhanced sodium sensitivity and disturbed circadian rhythm of blood pressure in essential hypertension. J Hypertens 2006; 24: 1647–1632.

  5. 5

    Kimura G, Frem G J, Brenner BM : Renal mechanism of salt sensitivity in hypertension. Curr Opin Nephrol Hypertens 1994; 3: 1–12.

  6. 6

    Uzu T : Circadian rhythm of blood pressure and cardiovascular risk in sodium sensitive hypertension. Clin Exp Nephrol 1999; 3: 229–236.

  7. 7

    Kimura G, Uzu T, Nakamura S, Inenaga T, Fujii T : High sodium sensitivity and glomerular hypertension/hyperfiltration in primary aldosteronism. J Hypertens 1996; 14: 1463–1468.

  8. 8

    Konishi Y, Okada N, Okamura M, et al: Sodium sensitivity of blood pressure appearing before hypertension and related to histological damage in immunoglobulin a nephropathy. Hypertension 2001; 38: 81–85.

  9. 9

    Koomans HA, Roos JC, Boer P, Geyskes GG, Mees EJ : Salt sensitivity of blood pressure in chronic renal failure. Evidence for renal control of body fluid distribution in man. Hypertension 1982; 4: 190–197.

  10. 10

    Kimura K : Effects of benidipine hydrochloride on renal arterioles. Ther Res 1994; 15: 411–414.

  11. 11

    Morikawa T, Okumura M, Konishi Y, Okada N, Imanishi M : Effects of benidipine on glomerular hemodynamics and proteinuria in patients with nondiabetic nephropathy. Hypertens Res 2002; 25: 571–576.

  12. 12

    Uzu T, Kazembe FS, Ishikawa K, Nakamura S, Inenaga T, Kimura G : High sodium sensitivity implicates nocturnal hypertension in essential hypertension. Hypertension 1996; 28: 139–142.

  13. 13

    Uzu T, Ishikawa K, Fujii T, Nakamura S, Inenaga T, Kimura G : Sodium restriction shifts circadian rhythm of blood pressure from nondipper to dipper in essential hypertension. Circulation 1997; 96: 1859–1862.

  14. 14

    Fujii T, Uzu T, Nishimura M, et al: Circadian rhythm of natriuresis is disturbed in nondipper type of essential hypertension. Am J Kidney Dis 1999; 33: 29–35.

  15. 15

    Kimura G, Imanishi M, Sanai T, et al: Intrarenal hemodynamics in patients with essential hypertension. Circ Res 1991; 69: 421–428.

  16. 16

    Bigazzi R, Bianchi S, Baldari D, Sgherri G, Baldari G, Campese VM : Microalbuminuria in salt-sensitive patients. A marker for renal and cardiovascular risk factors. Hypertension 1994; 23: 195–199.

  17. 17

    Gomez DM : Evaluation of renal resistance with special reference to changes in essential hypertension. J Clin Invest 1951; 30: 1143–1155.

  18. 18

    Carmines PK, Navar LG : Disparate effects of Ca channel blockers on afferent and efferent arteriolar responses to ANG II. Am J Physiol 1989; 256: F1015–F1020.

  19. 19

    Fleming JT, Parekh N, Steinhausen M : Calcium antagonists preferentially dilate preglomerular vessels of hydronephrotic kidney. Am J Physiol 1987; 253: F1157–F1163.

  20. 20

    Richard S : Vascular effects of calcium channel antagonists: new evidence. Drugs 2005; 65: S1–S10.

  21. 21

    Okumura M, Masada M, Yoshida Y, et al: Decrease in tetrahydrobiopterin as a possible cause of nephropathy in type II diabetic rats. Kidney Int 2006; 70: 401–406.

  22. 22

    Feng MG, Navar LG : Nitric oxide synthase inhibition activates L- and T-type Ca2+ channels in afferent and efferent arterioles. Am J Physiol Renal Physiol 2006; 290: F873–F879.

  23. 23

    Hirooka Y, Kimura Y, Nozoe M, Sagawa Y, Ito K, Sunagawa K : Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats. Hypertens Res 2006; 29: 49–56.

  24. 24

    Yasunari K, Maeda K, Nakamura M, Watanabe T, Yoshikawa J : Benidipine, a long-acting calcium channel blocker, inhibits oxidative stress in polymorphonuclear cells in patients with essential hypertension. Hypertens Res 2005; 28: 107–112.

  25. 25

    Fortepiani LA, Rodrigo E, Ortiz MC, et al: Pressure natriuresis in nitric oxide-deficient hypertensive rats: effect of antihypertensive treatments. J Am Soc Nephrol 1999; 10: 21–27.

Download references

Author information

Correspondence to Takashi Fujii.

Additional information

Department of Internal Medicine and Pathophysiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Uzu, T., Nishimura, M., Fujii, T. et al. Benidipine Attenuates Glomerular Hypertension and Reduces Albuminuria in Patients with Metabolic Syndrome. Hypertens Res 30, 161–165 (2007) doi:10.1291/hypres.30.161

Download citation

Keywords

  • benidipine
  • renal hemodynamics
  • albuminuria
  • metabolic syndrome

Further reading