RESUMO
OBJECTIVE: To investigate the effects of advanced glycation end-products (AGEs) on transient cytosolic free calcium in neonatal rat cardiac myocytes (CMs) cultured in vitro. METHODS: CMs cultured for 3 to 5 days in vitro were incubated with Ca(2+)-sensitive fluorescent indicator Fluo-3AM with light screening at 37 degrees celsius; with 5% CO(2) for 60 min. Changes of the fluorescence signal of free calcium caused by AGEs were measured under laser scanning confocal microscope (LSCM). RESULTS: Compared with the control cells, AGEs caused an increase in the concentration of cytosolic free calcium in a dose-dependent manner. CONCLUSION: AGEs may impair neonatal rat CMs by altering cytosolic free calcium concentration.
Assuntos
Cálcio/metabolismo , Produtos Finais de Glicação Avançada/farmacologia , Miócitos Cardíacos/metabolismo , Compostos de Anilina , Animais , Animais Recém-Nascidos , Canais de Cálcio/metabolismo , Células Cultivadas , Citosol/metabolismo , Indicadores e Reagentes , Miócitos Cardíacos/citologia , Ratos , Ratos Sprague-Dawley , XantenosRESUMO
OBJECTIVE: To investigate effects of captopril and losartan on the expression of kidney aquaporin-2 (AQP2) mRNA and the excretion of urine AQP2 in rats. METHODS: Thirty healthy rats were randomized into 3 groups, namely the control group, captopril group and losartan group, respectively. Blood and urine samples were collected from the rats for detecting serum Na(+), urine volume and urine osmolality in the course of medication. Urine AQP2 concentration was measured by enzyme-linked immunosorbent assay (ELISA). Semi-quantitative RT-PCR was performed for measurement of kidney inner medullary AQP2 and vasopressin V(2) receptor mRNA. RESULTS: Urine volume was increased in rats of captopril and losartan groups as compared with that of the control group. However, urine osmolality was lower in captopril group than in the other two groups (P<0.05). RT-PCR revealed decreased quantity of the inner medullary AQP2 mRNA of the captopril group than that of the other two groups, but the quantity of V(2) receptor mRNA did not differ significantly between the 3 groups. Urine AQP2 concentration was significantly higher in captopril group than in the control (P<0.05) and losartan groups (P0<0.01). CONCLUSION: Captopril can reduce the expression of the kidney inner medullary AQP2 mRNA and accelerate the excretion of the urine AQP2 in normal rats.
Assuntos
Aquaporina 2/biossíntese , Aquaporina 2/urina , Captopril/farmacologia , Rim/metabolismo , Losartan/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Aquaporina 2/genética , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Sclederma of Poria cocos (Hoelen) has been used as a diuretic in traditional Asian medicine. However, the underlying mechanism by which Sclederma of Poria cocos (hoelen) exerts its diuretic effect has not been well identified. The aim of the present study was to evaluate the effects of Sclederma of Poria cocos (hoelen) in rats with chronic heart failure (CHF) induced by acute myocardial infarction and to investigate the underlying mechanisms. MATERIALS AND METHODS: An aqueous extract of Sclederma of Poria cocos (hoelen) (2.4 g/kg/d, 1.2 g/kg/d or 0.6 g/kg/d) or furosemide (20 mg/kg/d) was administered orally to male Sprague-Dawley rats starting on the day of coronary ligation. The urine output of all rats was quantified and collected every day for 1 or 4 weeks. The expression of aquaporin-2 (AQP2) was examined after treatment for 1 or 4 weeks. RESULTS: Urinary output increased significantly and urinary osmolality decreased after oral administration of Sclederma of Poria cocos (hoelen) for both 1 and 4 weeks. Sclederma of Poria cocos (hoelen) caused less electrolyte disorder than furosemide. Furthermore, Sclederma of Poria cocos (hoelen) reduced the levels of plasma BNP in CHF rats, whereas furosemide had no effect. Importantly, both mRNA and protein expression of AQP2 were down-regulated and urinary excretion of AQP2 was decreased after administration of Sclederma of Poria cocos (hoelen) to CHF rats. Similarly, Sclederma of Poria cocos (hoelen) reduced plasma arginine vasopressin (AVP) level and down-regulated vasopressin type 2 receptor (V2R) mRNA expression. CONCLUSIONS: Sclederma of Poria cocos (hoelen) exerts its diuretic effect and improves cardiac function in CHF rats via the AVP-V2R-AQP2 axis.