90-kDa N-domain angiotensin I-converting enzyme (ACE): possible marker for hypertension in a renal transplant model.

INTRODUCTION: Hypertension is nearly universal in kidney transplant and several factors are associated with post transplant hypertension, including immunosuppressive medications and genetic predisposition. OBJECTIVE: The aims were to evaluate the effects of spontaneously hypertensive rats (SHR) kidney transplantation in Wistar rats and the possible transference of 80/90-kDa N-domain ACE. METHODS: To do so, the data from Wistar recipients of kidney from SHR were compared to data from transplanted Wistar submitted to CsA treatment and, to Wistar Sham. RESULTS AND DISCUSSION: Despite the unaltered blood pressure observed at early stages, 80/90-kDa ACE was found expressed in the urine of rats 7 and 15 days after transplantation, which was intense when rats became hypertensive 30 days post-surgery. CONCLUSION: Our data show that this enzyme is associated with the development of hypertension, and this marker appears in the urine before any substantial blood pressure alteration.

HSP70 induced by hyperosmotic stress partially protects LLC-PK1 cells against nephrotoxic drugs.

Accumulation of HSP70 is related to the cytoprotection. It was evaluated whether hyperosmotic stress induces HSP70 accumulation in LLC-PK1 cells, and protects cells against toxicity provoked by cisplatin (Cis) and cyclosporine A (CyA). Cells were maintained in isosmotic (Iso) or hyperosmotic (H) culture medium for 24 h and then exposed to Cis or CyA for an additional period of 12 or 24 h (groups H+Cis and H+CyA). The H medium did not induce cell death and increased both HSP70 mRNA and protein levels, suggesting a role in cell adaptation to H condition. H medium produced partial cytoprotection against Cis and CyA compared with control cells. Despite the cytoprotection, there was a reduction in HSP70 mRNA and protein levels in H+Cis group. In contrast, the H+CyA group presented high levels of HSP70 mRNA and protein. The induction of HSP70 by H medium was associated with tolerance of LLC-PK1 cells against Cis and CyA cytotoxicity but this protection was induced by different mechanisms and depended on the characteristics of the drug used.

90-kDa N-domain angiotensin I-converting enzyme (ACE): possible marker for hypertension in a renal transplant model / Enzima conversora de angiotensina I (ECA) N-domínio 90-kDa: possível marcador para hipertensão em modelo de transplante renal

Abstract Introduction: Hypertension is nearly universal in kidney transplant and several factors are associated with post transplant hypertension, including immunosuppressive medications and genetic predisposition. Objective: The aims were to evaluate the effects of spontaneously hypertensive rats (SHR) kidney transplantation in Wistar rats and the possible transference of 80/90-kDa N-domain ACE. Methods: To do so, the data from Wistar recipients of kidney from SHR were compared to data from transplanted Wistar submitted to CsA treatment and, to Wistar Sham. Results and Discussion: Despite the unaltered blood pressure observed at early stages, 80/90-kDa ACE was found expressed in the urine of rats 7 and 15 days after transplantation, which was intense when rats became hypertensive 30 days post-surgery. Conclusion: Our data show that this enzyme is associated with the development of hypertension, and this marker appears in the urine before any substantial blood pressure alteration.

Resumo Introdução: A hipertensão é altamente prevalente pós-transplante renal e vários fatores estão associados incluindo o tratamento com imunossupressores e a predisposição genética. Objetivo: Os objetivos foram avaliar os efeitos do transplante do rim de ratos espontaneamente hipertensos (SHR) em ratos Wistar, e a possível transferência da ECA N-domínio de 80/90-kDa para os tecidos dos receptores. Métodos: Para isso, os dados dos animais Wistar receptores dos rins de SHR foram comparados aos dados dos Wistar submetidos ao tratamento com CsA e Wistar Sham. Resultados e Discussão: Apesar da pressão arterial permanecer inalterada nos estágios iniciais pós-transplante renal, a expressão da ECA de 80/90-kDa foi identificada na urina de ratos 7 e 15 dias após o transplante, e de forma mais intensa aos 30 dias após a cirurgia, quando os animais tornaram-se hipertensos. Conclusão: Nossos dados mostram que ECA N-domínio está associada ao desenvolvimento da hipertensão, e que este marcador pode ser identificado na urina pós-transplante renal antes mesmo de qualquer alteração da pressão arterial.

Renin similar to the submaxillary gland form is expressed in mouse mesangial cells: subcellular localization and all generation under control and glucose-stimulated conditions.

It was analyzed the forms of renin produced by a mouse immortalized mesangial cell line (MIC) and their ability to generate angiotensin II (AII). The synthesis, localization and secretion of renin and AII by MIC were evaluated under conditions of normal (10 mM) or high (30 mM) glucose concentration. Two major bands of 35 kDa and 70 kDa were observed in SDS-PAGE. The amino-terminal sequencing revealed the presence of prorenin and renin in these bands with higher homology with the submaxillary gland form of renin. Renin and AII were detected in cell lysate and in culture medium, indicating that MIC synthesize and secrete these peptides. Renin was localized in the cytoplasm while AII was seen predominantly inside the nucleus. High glucose induced an increase in the synthesis and secretion of renin and AII. Results suggest that MIC produce AII and a renin form similar to the submandibular. Intracellular AII may be directed at the nucleus and/or be secreted, indicating that AII may directly influences gene expression in these cells. The mechanisms of synthesis and secretion of renin and AII are potentially modified by high glucose concentration, suggesting a possible role of AII produced by mesangial cells in diabetic nephropathy.