Pioglitazone, peroxisome proliferator-activated receptor (PPAR-γ) agonist, is a therapeutic drug for diabetes. Present study investigated the interaction between PPAR-γ and alpha adrenoceptors in modulating vasopressor responses to Angiotensin II (Ang II) and adrenergic agonists, in diabetic & non-diabetic Spontaneously Hypertensive Rats (SHRs). Diabetes was induced with an i.p injection of streptozotocin (40 mg/kg) in two groups (STZ-CON, STZ-PIO), whereas two groups remained non diabetic (ND-CO, ND-PIO). One diabetic and non-diabetic group received Pioglitazone (10mg/kg) orally for 21 days. On day 28, the animals were anaesthetized with sodium pentobarbitone (60mg/kg) and prepared for measurement of systemic haemodynamics. Basal mean arterial pressure of STZ-CON was higher than ND-CON, whereas following pioglitazone treatment, MAP was lower compared to respective controls. MAP responses to i.v administration of NA, PE, ME and ANG II were significantly lower in diabetic SHRs: STZ-CON vs ND-CON (35%). Pioglitazone significantly decreased responses to NA, PE, ME and ANG II in ND-PIO versus ND-CON by 63%. Responses to NA and ANG II were significantly attenuated in STZ-PIO vs. ND-PIO (40%). PPAR-γ regulates systemic hemodynamic in diabetic model and cross-talk relationship exists between PPAR-γ and α1-adrenoceptors, ANG II in systemic vasculature of SHRs.

译文

吡格列酮,过氧化物酶体增殖物激活受体 (PPAR-γ) 激动剂,是糖尿病的治疗药物。本研究调查了在糖尿病和非糖尿病自发性高血压大鼠 (shr) 中,PPAR-γ 和 α 肾上腺素受体之间的相互作用,以调节血管升压剂对血管紧张素II (Ang II) 和肾上腺素能激动剂的反应。两组 (STZ-CON,STZ-PIO) 通过静脉注射链脲佐菌素 (40 mg/kg) 诱发糖尿病,而两组仍为非糖尿病 (ND-CO,ND-PIO)。一个糖尿病和非糖尿病组口服吡格列酮 (10 mg/kg) 21天。在第28天,用戊巴比妥钠 (60 mg/kg) 麻醉动物,并准备用于测量全身血液动力学。STZ-CON的基础平均动脉压高于ND-CON,而在吡格列酮治疗后,MAP低于相应的对照组。在糖尿病shr: STZ-CON vs ND-CON (35%) 中,对NA,PE,ME和ANG II的iv给药的MAP响应显着降低。通过63%,吡格列酮显着降低了ND-PIO与ND-CON对NA,PE,ME和ANG II的反应。对NA和ANG II的反应在STZ-PIO与ND-PIO (40%) 中显著减弱。PPAR-γ 调节糖尿病模型中的全身血液动力学,并且在shr的全身脉管系统中,PPAR-γ 和 α1-肾上腺素受体ANG II之间存在串扰关系。

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