FK-506 - EFFECTS ON GLOMERULAR HEMODYNAMICS and ON MESANGIAL CELLS in CULTURE

FK-506 - EFFECTS ON GLOMERULAR HEMODYNAMICS and ON MESANGIAL CELLS in CULTURE

Autor Hadad, Semiramis J. Google Scholar
Souza, Edison RM Google Scholar
Ferreira, Alice Teixeira Autor UNIFESP Google Scholar
Oshiro, Maria E M Google Scholar
Boim, Mirian Aparecida Autor UNIFESP Google Scholar
Razvickas, Clara V. Google Scholar
Moura, Luiz AR Google Scholar
Schor, Nestor Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo FK 506 is a new immunosuppressive drug that, like cyclosporine A (CsA), presents nephrotoxicity. Glomerular hemodynamic studies showed that acute FK 506 infusion (N = 9, 3 mg/kg body wt, i.v. in bolus) caused a 57% reduction in glomerular filtration rate (GFR) (0.74 +/- 0.03 to 0.32 +/- 0.02 ml/min, P < 0.05) and a 40% reduction in single nephron glomerular filtration rate (SNGFR; 43.0 +/- 5.2 to 26.0 +/- 2.5 nl/min, P < 0.05) due to a 25% reduction in glomerular plasma flow rate (Q(A)) (133.4 +/- 19.8 to 99.8 +/- 12.0 nl/min) and a 22% reduction in glomerular ultrafiltration coefficient (K-f; 0.1009 +/- 0.0203 to 0.0790 +/- 0.0130 nl/sec . mm Hg). After 10 days of FK treatment (N = 8, 0.6 mg/kg body wt, i.p.), we observed a reduction of 23% in GFR (0.97 +/- 0.02 to 0.75 +/- 0.04 ml/min, P < 0.05) and of 23% in SNGFR (37.9 +/- 3.0 to 29.1 +/- 1.9 nl/min, P < 0.05) due to a 42% reduction in K-f (0.1486 +/- 0.0101 to 0.0870 +/- 0.0110 nl/sec . mm Hg, P < 0.05) and a 38% reduction in Q(A) (117.6 +/- 10.2 to 73.5 +/- 6.1 nl/min, P < 0.05). the latter was consequent to the increment of 72% in total arteriolar resistance (R(T)) (3.1 +/- 0.2 to 5.2 +/- 0.5 +/- 0.5 10(10) . dyn . sec . cm(-5), P < 0.05). Thus, the pattern of FK 506 effect on glomerular hemodynamics was similar in both acute and chronic treatments. Additionally, in order to evaluate the effect of FK 506 on mesangial cells (MC), we performed studies measuring intracellular calcium concentration ([Ca2+](i)) with Fura-2/AM as well as MC contraction by morphometric analysis. It was observed that FK 506 increases the [Ca2+](i) (R 340/380: 2.5 +/- 0.3 to 3.8 +/- 0.4, P < 0.05) due to mobilization of the extracellular calcium pool, via opening calcium type L voltage dependent channels, since verapamil blunted the increases of [Ca2+](i) caused by FK 506 (R 340/380: 3.5 +/- 0.9 to 2.8 +/- 0.8). the [Ca2+](i) was not changed after FK 506 incubation of MC with verapamil and thapsigargin, and thus no calcium release-activated channel (CRAC) was affected. the increase of [Ca2+](i) induced by FK 506 probably caused contraction of MC evaluated by reduction of the cross sectional area from 3772 +/- 106 to 1912 +/- 61 mu m(2) (P < 0.05). Thus, FX 506 caused a reduction in SNGFR by reducing Q(A) and K-f after both acute and chronic administration, and the mesangial cells potentially participate in this nephrotoxicity via reduction in K-f mainly during chronic treatment.
Idioma Inglês
Data de publicação 1995-07-01
Publicado em Kidney International. Cambridge: Blackwell Science Publ Inc Cambridge, v. 48, n. 1, p. 56-64, 1995.
ISSN 0085-2538 (Sherpa/Romeo, fator de impacto)
Publicador Blackwell Science Publ Inc Cambridge
Extensão 56-64
Fonte http://dx.doi.org/10.1038/ki.1995.267
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:A1995RF61500007
Endereço permanente http://repositorio.unifesp.br/handle/11600/25508

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