Ge Chang, Garcia Raul, Anand-Srivastava Madhu B
Department of Physiology, Faculty of Medicine, University of Montreal, C.P. 6128, Succ. Centre-ville, Montreal, QC H3C 3J7, Canada.
Can J Physiol Pharmacol. 2006 Jul;84(7):739-46. doi: 10.1139/y05-123.
We have previously shown the augmented levels of Gialpha-2 and Gialpha-3 proteins (isoforms of inhibitory guanine nucleotide regulatory protein (G-protein)), and not of Gsalpha, in the hearts and aortas of spontaneously and experimentally induced hypertensive rats. The increased expression of Gialpha and blood pressure was restored toward WKY levels by captopril treatment, suggesting a role for angiotensin (Ang) II in the enhanced expression of Gialpha protein and blood pressure. This study was undertaken to investigate whether 1 kidney 1 clip (1K-1C) hypertensive rats that exhibit enhanced levels of Ang II also express enhanced levels of Gialpha proteins. Aortas from 1K-1C hypertensive rats were used. The expression of G-proteins was determined at protein levels with immunoblotting techniques, using specific antibodies for different isoforms of G-proteins. The levels of Gialpha-2 and Gialpha-3 proteins were significantly higher in aortas from 1K-1C hypertensive rats than in control rats; Gsalpha levels were unchanged. The inhibitory effect of low concentrations of guanosine 5'-[gamma-thio]triphosphate (GTPgammaS) on forskolin (FSK)-stimulated adenylyl cyclase (AC) activity was significantly enhanced in aortas from 1K-1C hypertensive rats; the inhibitory effect of C-ANP(4-23), which specifically interacts with the atrial natriuretic peptide (ANP)-C receptor, and Ang II on AC was attenuated. GTPgammaS, isoproterenol, glucagon, NaF, and FSK stimulated the AC activity in aortas from control and hypertensive rats to varying degrees; however, the stimulations were significantly lower in hypertensive rats than in control rats. These data suggest that aortas from 1K-1C hypertensive rats exhibit enhanced expression of Gialpha proteins and associated functions.
我们之前已经表明，在自发性和实验性高血压大鼠的心脏和主动脉中，Gialpha - 2和Gialpha - 3蛋白（抑制性鸟嘌呤核苷酸调节蛋白（G蛋白）的亚型）水平升高，而Gsalpha蛋白水平未升高。卡托普利治疗可使Gialpha蛋白表达增加和血压恢复至WKY水平，提示血管紧张素（Ang）II在Gialpha蛋白表达增强和血压升高中起作用。本研究旨在探讨表现出Ang II水平升高的单肾单夹（1K - 1C）高血压大鼠是否也表达升高水平的Gialpha蛋白。使用了1K - 1C高血压大鼠的主动脉。采用免疫印迹技术，使用针对不同G蛋白亚型的特异性抗体，在蛋白水平测定G蛋白的表达。1K - 1C高血压大鼠主动脉中Gialpha - 2和Gialpha - 3蛋白水平显著高于对照大鼠；Gsalpha水平未改变。低浓度鸟苷5'-[γ-硫代]三磷酸（GTPγS）对福斯可林（FSK）刺激的腺苷酸环化酶（AC）活性的抑制作用在1K - 1C高血压大鼠主动脉中显著增强；特异性与心钠素（ANP）- C受体相互作用的C - ANP(4 - 23)和Ang II对AC的抑制作用减弱。GTPγS、异丙肾上腺素、胰高血糖素、NaF和FSK对对照大鼠和高血压大鼠主动脉中的AC活性有不同程度的刺激作用；然而，高血压大鼠中的刺激作用显著低于对照大鼠。这些数据表明，1K - 1C高血压大鼠的主动脉表现出Gialpha蛋白表达增强及相关功能改变。
