RESUMO
Hypertensive renal damage generally occurs during the middle and late stages of hypertension, which is typically characterized by proteinuria and renal inflammation. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been widely used for therapy of arterial hypertension and cardiovascular diseases. However, the protective effects of captopril on hypertension-induced organ damage remain elusive. The present study was designed to explore the renoprotective action of captopril in spontaneously hypertensive rats (SHR). The 6-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into long-term captopril-treated (34 mg/kg) and vehicle-treated groups. The results showed that in SHR there was obvious renal injury characterized by the increased levels of urine albumin, total protein, serum creatinine, blood urea nitrogen, renal inflammation manifested by the increased mRNA and protein expression of inflammatory factors including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and inducible nitric oxide synthase, and enhanced nuclear factor-κB (NF-κB) activation. Captopril treatment could lower blood pressure, improve renal injury, and suppress renal inflammation and NF-κB activation in SHR rats. In conclusion, captopril ameliorates renal injury and inflammation in SHR possibly via inactivation of NF-κB signaling.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Captopril/uso terapêutico , Hipertensão/tratamento farmacológico , NF-kappa B/efeitos dos fármacos , Nefrite/prevenção & controle , Proteinúria/prevenção & controle , Animais , Hipertensão/complicações , Masculino , Nefrite/etiologia , Proteinúria/etiologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de SinaisRESUMO
Hypertensive renal damage generally occurs during the middle and late stages of hypertension, which is typically characterized by proteinuria and renal inflammation. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been widely used for therapy of arterial hypertension and cardiovascular diseases. However, the protective effects of captopril on hypertension-induced organ damage remain elusive. The present study was designed to explore the renoprotective action of captopril in spontaneously hypertensive rats (SHR). The 6-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into long-term captopril-treated (34 mg/kg) and vehicle-treated groups. The results showed that in SHR there was obvious renal injury characterized by the increased levels of urine albumin, total protein, serum creatinine, blood urea nitrogen, renal inflammation manifested by the increased mRNA and protein expression of inflammatory factors including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase, and enhanced nuclear factor-κB (NF-κB) activation. Captopril treatment could lower blood pressure, improve renal injury, and suppress renal inflammation and NF-κB activation in SHR rats. In conclusion, captopril ameliorates renal injury and inflammation in SHR possibly via inactivation of NF-κB signaling.
Assuntos
Animais , Masculino , Ratos , Proteinúria/prevenção & controle , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/uso terapêutico , NF-kappa B/efeitos adversos , Hipertensão/tratamento farmacológico , Nefrite/prevenção & controle , Anti-Hipertensivos/uso terapêutico , Proteinúria/etiologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de Sinais , Hipertensão/complicações , Nefrite/etiologiaRESUMO
BACKGROUND: Osteoarthritis (OA) is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented. RESULTS: In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1) and receptor chemokine (C-C motif) receptor 2 (CCR2) in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001) and the expression of MMP-13 also increased (P < 0.05). MCP-1 stimulation also induced (or enhanced) the apoptosis of OA chondrocytes (P < 0.05). Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13) in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA) model. CONCLUSIONS: The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis.
Assuntos
Quimiocina CCL2/metabolismo , Condrócitos/metabolismo , Osteoartrite do Joelho/fisiopatologia , Receptores CCR2/metabolismo , Adolescente , Idoso , Animais , Apoptose/fisiologia , Quimiocina CCL2/genética , Condrócitos/enzimologia , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Fibroblastos/metabolismo , Humanos , Técnicas In Vitro , Ácido Iodoacético , Masculino , Proteínas Matrilinas/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Receptores CCR2/antagonistas & inibidores , Receptores CCR2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Membrana Sinovial/citologia , Adulto JovemRESUMO
BACKGROUND: Osteoarthritis (OA) is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented. RESULTS: In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1) and receptor chemokine (C-C motif) receptor 2 (CCR2) in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001) and the expression of MMP-13 also increased (P < 0.05). MCP-1 stimulation also induced (or enhanced) the apoptosis of OA chondrocytes (P < 0.05). Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13) in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA) model. CONCLUSIONS: The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis.