RESUMO
The role of hyperglycaemia in the pathogenesis of hypotension in diabetic disorders was investigated using the changes in cardiac M(2)-muscarinic receptor (M(2)-mAChR) gene expression in type-1-like diabetic rats and cultured cardiomyocytes. Blood pressure was markedly decreased in diabetic rats following the intravenous injection of streptozotocin (STZ) for 8 weeks. Also, the baroreflex sensitivity (Delta HR/Delta BP), as measured by the changes in heart rate (Delta HR) and mean blood pressure (Delta BP) 1 min after the intravenous injection of phenylephrine (10 microg/kg), was significantly increased. Arecaidine propargyl ester (APE), a M(2)-mAChR agonist produced a marked reduction in heart rate in these diabetic rats. Normalization of plasma glucose in diabetic rats using insulin (0.5 IU) or phlorizin (1 mg/kg) injection attenuated the blood pressure reduction and reversed the mRNA and protein levels of cardiac M(2)-mAChR. A high concentration of glucose (20 mmol/l) directly influenced the increase in gene expression of M(2)-mAChR in the H9c2 cardiac cell line. Hyperglycaemia induced an increase in cardiac M(2)-mAChR gene expression, suggesting a role in the pathogenesis of hypotension in diabetic disorders.
Assuntos
Diabetes Mellitus Tipo 1/patologia , Hiperglicemia/patologia , Hipotensão/patologia , Animais , Arecolina/análogos & derivados , Arecolina/farmacologia , Barorreflexo , Linhagem Celular , Agonistas Colinérgicos/farmacologia , Diabetes Mellitus Experimental , Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Hiperglicemia/complicações , Hipotensão/etiologia , Insulina/uso terapêutico , Masculino , Fenilefrina , Florizina/uso terapêutico , RNA Mensageiro/análise , Ratos , Ratos Wistar , Receptor Muscarínico M2/análise , Receptor Muscarínico M2/genética , Receptor Muscarínico M2/metabolismoRESUMO
Changes of cardiac M2-muscarinic receptor (M2-mAChR) gene expression was investigated in type-1 like diabetic rats induced by intravenous injection of streptozotocin (STZ) and type-2 like diabetic rats induced by fed with fructose-rich chow. Systolic blood pressure (SBP) in STZ-diabetic rats was significantly lower than that in age-matched non-diabetic rats, while the SBP in type-2 like diabetic rats was higher than in non-diabetic rats. Also, the mRNA or protein level of cardiac M2-mAChR in STZ-diabetic rats was markedly higher than non-diabetic rats, but it was not observed in type-2 like diabetic rats as compared to age-matched non-diabetic rats. Arecaidine propargyl ester (APE), the agonist of M2-mAChR, produced a marked reduction of heart rate in STZ-diabetic rats but made less influence on heart rate in fructose-fed rats or non-diabetic rats. The results suggest that cardiac M2-mAChR gene expression is raised in type-1 like diabetic rats but not in type-2 like diabetic rats, this difference mainly due to hyperglycemia, for the production of hypotension in diabetic disorders.
Assuntos
Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/patologia , Regulação da Expressão Gênica/fisiologia , Miocárdio/metabolismo , Receptor Muscarínico M2/metabolismo , Animais , Arecolina/análogos & derivados , Arecolina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 2/etiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Frutose/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor Muscarínico M2/genética , EstreptozocinaRESUMO
Ginsenoside, the active principles in Panax ginseng root, has been demonstrated to show neurotrophic and neuroprotective actions for prevention of neuron degeneration. Deposition of beta-amyloid peptide (Abeta) causes neurotoxicity through the formation of plaques in brains with Alzheimer's disease. Pituitary adenylate cyclase-activating polypeptide (PACAP) is introduced as a neurotrophic factor to promote cell survival. However, effect of Rh2, one of ginsenosides, on PACAP expression induced by Abeta remains unclear. In the present study, we found that Rh2 stimulates PACAP gene expression and cell proliferation in type I rat brain astrocytes (RBA1) cells and both effects were not modified by the estrogen antagonists (MPP or ICI 182780). Also, Rh2 ameliorates the RBA1 growth inhibition of Abeta. Moreover, blockade of PACAP receptor PAC1 using PACAP (6-38) inhibits all the actions of Rh2. These results suggest that Rh2 can induce an increase of PACAP to activate PAC1, but not estrogen receptor, and thereby leads to attenuate Abeta-induced toxicity. Thus, ginseng seems useful in the prevention of dementia.
