Aim: Ischemia and reperfusion (IR) injury is a serious problem that is occured during thrombolytic therapy, organ transplantation, coronary angioplasty, and cardiopulmonary bypass. There is an increase in the number o...Aim: Ischemia and reperfusion (IR) injury is a serious problem that is occured during thrombolytic therapy, organ transplantation, coronary angioplasty, and cardiopulmonary bypass. There is an increase in the number of AT2 receptors in some pathological conditions such as cardiac hypertrophy, myocardial infarction, congestive heart failure. This study was designed to investigate the effects AT2 receptor agonist Novokinin on infarct size, caveolin-1 (CAV-1), HSP90, ADMA, NADPH oxidase and Rhokinase associated to endothelial dysfunction and oxidative stress, and NFκB and TLR-4 levels induced by inflammation on myocardial IR. Methods: The experimental groups: Sham (C), Novokinin (N), IR and IRN. Novokinin was performed with infusion pump before ischemia, and during IR. The left main coronary artery was occluded for 30 minutes ischemia followed by 120 minutes reperfusion in anesthetized rats. CAV-1, HSP90, and NFκB levels were measured by the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), ADMA, TLR-4, NADPH oxidase, and Rhokinase levels were measured by ELISA, infarct size was measured by ImageJ, an image analysis software, in the heart tissue. Results: NFκB, HSP90, NADPH oxidase and TLR-4 levels increased with IR and significantly decreased with Novokinin. CAV-1 levels were not different between the groups. ADMA and Rhokinase levels were increased due to IR but decreased with Novokinin. Novokinin reduced infarct size due to IR. Conclusion: Our results showed that, ADMA, HSP90, NFκB, TLR-4, Rhokinase, and NADPH oxidase levels play important roles on IR injury. AT2 receptor agonist Novokinin may affect positively oxidative changes, inflammation, and endothelial function in myocardial IR injury.展开更多
The loss of balance between the antagonistic activities of angiotensin II AT1/AT2 receptors has been impli-cated as a major mediator in the development of hypertension and progressive nephropathy in expe-rimental diab...The loss of balance between the antagonistic activities of angiotensin II AT1/AT2 receptors has been impli-cated as a major mediator in the development of hypertension and progressive nephropathy in expe-rimental diabetes. The present study was designed to investigate the potential of garlic to modulate the level of expression of the AT2 receptor in the adrenal and renal tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven specificity to the AT2 receptor, as verified by Western blotting and emplo- yed in immunohistochemical assays, indicated that compared to normal rats, the highest adrenocortical AT2 receptor expression was significantly shifted from the zona glomerulosa to the zona fasciculate/ reticularis, and was significantly reduced in adrenomedul- lary chromaffin cells of control diabetic rats. In the kidney, STZ treatments were associated with a signi- ficant decrease in AT2 receptor expression throughout glomeruli and all cortical and medullary tubular segments. Compared to control diabetic rats, the labeling of the AT2 receptor in the garlic-treated diabetic group was restored among adrenocortical zona glomerulosa cells and adrenomedullary chromaffin cells and significantly reduced in the zona fasiculata, and was also restored in glomeruli and throughout renal cortical and medullary tubular segments, to le- vels comparable to those observed in normal rats. The capacity of garlic to modulate diabetes-induced AT2 receptor down-regulation may be implicated in restoring the recuperative processes mediated by AT2 receptors, which interfere with the development of hypertension and nephropathy.展开更多
血管紧张素Ⅱ2型受体(angiotensin Ⅱ type 2 receptor,AT2受体)是近年的研究热点,其主要发挥拮抗血管紧张素Ⅱ1型受体(AT1受体)的作用,如调控血压、抑制心肌肥厚及纤维化、抑制血管重建、保护心功能等心血管效应。但尚存在一些研究不...血管紧张素Ⅱ2型受体(angiotensin Ⅱ type 2 receptor,AT2受体)是近年的研究热点,其主要发挥拮抗血管紧张素Ⅱ1型受体(AT1受体)的作用,如调控血压、抑制心肌肥厚及纤维化、抑制血管重建、保护心功能等心血管效应。但尚存在一些研究不支持以上结论,这可能与AT2受体数量及功能在不同个体、组织类型、病理生理状态下存在差别有关。展开更多
文摘Aim: Ischemia and reperfusion (IR) injury is a serious problem that is occured during thrombolytic therapy, organ transplantation, coronary angioplasty, and cardiopulmonary bypass. There is an increase in the number of AT2 receptors in some pathological conditions such as cardiac hypertrophy, myocardial infarction, congestive heart failure. This study was designed to investigate the effects AT2 receptor agonist Novokinin on infarct size, caveolin-1 (CAV-1), HSP90, ADMA, NADPH oxidase and Rhokinase associated to endothelial dysfunction and oxidative stress, and NFκB and TLR-4 levels induced by inflammation on myocardial IR. Methods: The experimental groups: Sham (C), Novokinin (N), IR and IRN. Novokinin was performed with infusion pump before ischemia, and during IR. The left main coronary artery was occluded for 30 minutes ischemia followed by 120 minutes reperfusion in anesthetized rats. CAV-1, HSP90, and NFκB levels were measured by the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), ADMA, TLR-4, NADPH oxidase, and Rhokinase levels were measured by ELISA, infarct size was measured by ImageJ, an image analysis software, in the heart tissue. Results: NFκB, HSP90, NADPH oxidase and TLR-4 levels increased with IR and significantly decreased with Novokinin. CAV-1 levels were not different between the groups. ADMA and Rhokinase levels were increased due to IR but decreased with Novokinin. Novokinin reduced infarct size due to IR. Conclusion: Our results showed that, ADMA, HSP90, NFκB, TLR-4, Rhokinase, and NADPH oxidase levels play important roles on IR injury. AT2 receptor agonist Novokinin may affect positively oxidative changes, inflammation, and endothelial function in myocardial IR injury.
文摘The loss of balance between the antagonistic activities of angiotensin II AT1/AT2 receptors has been impli-cated as a major mediator in the development of hypertension and progressive nephropathy in expe-rimental diabetes. The present study was designed to investigate the potential of garlic to modulate the level of expression of the AT2 receptor in the adrenal and renal tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven specificity to the AT2 receptor, as verified by Western blotting and emplo- yed in immunohistochemical assays, indicated that compared to normal rats, the highest adrenocortical AT2 receptor expression was significantly shifted from the zona glomerulosa to the zona fasciculate/ reticularis, and was significantly reduced in adrenomedul- lary chromaffin cells of control diabetic rats. In the kidney, STZ treatments were associated with a signi- ficant decrease in AT2 receptor expression throughout glomeruli and all cortical and medullary tubular segments. Compared to control diabetic rats, the labeling of the AT2 receptor in the garlic-treated diabetic group was restored among adrenocortical zona glomerulosa cells and adrenomedullary chromaffin cells and significantly reduced in the zona fasiculata, and was also restored in glomeruli and throughout renal cortical and medullary tubular segments, to le- vels comparable to those observed in normal rats. The capacity of garlic to modulate diabetes-induced AT2 receptor down-regulation may be implicated in restoring the recuperative processes mediated by AT2 receptors, which interfere with the development of hypertension and nephropathy.
文摘血管紧张素Ⅱ2型受体(angiotensin Ⅱ type 2 receptor,AT2受体)是近年的研究热点,其主要发挥拮抗血管紧张素Ⅱ1型受体(AT1受体)的作用,如调控血压、抑制心肌肥厚及纤维化、抑制血管重建、保护心功能等心血管效应。但尚存在一些研究不支持以上结论,这可能与AT2受体数量及功能在不同个体、组织类型、病理生理状态下存在差别有关。
