Beneficial effects of calcium channel blockade on acute glomerular hemodynamic changes induced by cyclosporine

A. Fassi, F. Sangalli, F. Colombi, N. Perico, G. Remuzzi, A. Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

Experimental and human studies have documented that cyclosporine (CsA) acutely reduces glomerular filtration rate (GFR). It has been reported that this effect can be partially prevented by calcium (Ca) channel blockade; however, the mechanisms by which this combination exerts its beneficial effects are unknown. We evaluated glomerular ultrafiltration determinants during acute CsA administration in the rat. First, we determined that maximal whole-kidney functional changes occur between 120 and 150 minutes after CsA administration and confirmed that pretreatment of MWF rats with the Ca channel blocker lacidipine effectively prevents a reduction in GFR. Micropuncture measurements in CsA-treated animals showed that a reduction in GFR (0.49 ± 0.24 v 0.88 ± 0.26 mL/min; P <0.05; CsA-treated v untreated rats) is associated with a significant increase in glomerular capillary pressure (P(gc); 63.1 ± 2.1 v 52.8 ± 2.8 mm Hg; P <0.01) and efferent arteriolar resistance, whereas single-nephron (SN) GFR and ultrafiltration coefficient (K(f)) are both importantly reduced (34.0 ± 11.7 v 68.9 ± 23.8 nL/min; P <0.05 and 1.04 ± 0.33 v 4.40 ± 2.36 nL/min/mm Hg; P <0.01, respectively). Lacidipine partially prevented SNGFR (43.1 ± 14.3 nL/min) and K(f) decline (2.08 ± 1.10 nL/min/mm Hg) despite the presence of elevated P(gc). This study further documents that Ca channel blockade has favorable effects on CsA-induced acute renal dysfunction. The mechanism of protection includes the prevention of glomerular hemodynamic changes induced by CsA, mainly GFR decline and reduction in glomerular K(f).

Original languageEnglish
Pages (from-to)267-275
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume33
Issue number2
Publication statusPublished - 1999

Keywords

  • Cyclosporine
  • Glomerular capillary pressure
  • Glomerular filtration rate
  • Glomerular hemodynamics
  • MWF rat
  • Ultrafiltration coefficient

ASJC Scopus subject areas

  • Nephrology

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