Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA.
J Renin Angiotensin Aldosterone Syst. 2010 Dec;11(4):214-21. doi: 10.1177/1470320310379065. Epub 2010 Aug 31.
It has long been known that angiotensin type-1 receptors (AT1R) play a critical role in sympathetic regulation, cardiovascular activity, and hormone secretion under physiological and pathological states. On the other hand, the functional significance of angiotensin type-2 receptors (AT2R) is poorly understood. In a recent study we demonstrated that, in rats with chronic heart failure, AT1R protein expression was increased but AT2R expression was decreased in the rostral ventrolateral medulla (RVLM). This imbalance of angiotensin receptors contributed to sympatho-excitation in the heart failure state. In the current experiment, we measured AT1R and AT2R protein expressions in the brainstem, kidney and liver from male foetuses (3 days before birth), male neonates (3 days after birth), male and female adults (8 weeks) and male aged (28 months) rats by Western blot analysis. In the brainstem, we found that the foetuses and neonates exhibited a significantly lower AT2R protein expression compared with adult rats (foetus 0.08 ± 0.01, neonate 0.12 ± 0.01, male adult 0.25 ± 0.01, female adult 0.22 ± 0.02; n = 4 per group, p < 0.001 foetus and neonate compared with male or female adults). In contrast, the foetuses and neonates expressed significantly higher AT1R protein than that of the adults (foetus 0.64 ± 0.09, neonate 0.56 ± 0.01, male adult 0.13 ± 0.02, female adult 0.08 ± 0.02; n = 4 each group, p < 0.001 foetus and neonate compared with male and female adults). In the liver, the AT2R protein was also higher in foetus and neonate, than in adult rats. Interestingly, the foetal liver expressed higher AT1R protein compared with that of the neonate. In the kidney, AT2R expression was significantly increased with age (foetus 0.08 ± 0.01, neonate 0.19 ± 0.02, male adult 0.49 ± 0.04, female adult 0.90 ± 0.10; n = 4 per group, p < 0.01-0.001). AT1R expression, on the other hand, was higher in the foetuses than that in both neonate and male adults. This study provides data contrary to existing dogma that AT2R expression is higher in foetal life and low in adults, suggesting an involvement of a potentially important functional role for AT2R in adult animals and AT1R in foetal development and/or physiology.
长期以来，人们一直认为血管紧张素 1 型受体（AT1R）在生理和病理状态下的交感神经调节、心血管活动和激素分泌中起着关键作用。另一方面，血管紧张素 2 型受体（AT2R）的功能意义还知之甚少。在最近的一项研究中，我们发现在慢性心力衰竭大鼠中，血管紧张素受体的这种不平衡导致心力衰竭状态下的交感神经兴奋。在当前的实验中，我们通过 Western blot 分析测量了雄性胎儿（出生前 3 天）、雄性新生儿（出生后 3 天）、雄性和雌性成年（8 周）和雄性老年（28 个月）大鼠脑干、肾脏和肝脏中的 AT1R 和 AT2R 蛋白表达。在脑干中，我们发现胎儿和新生儿的 AT2R 蛋白表达明显低于成年大鼠（胎儿 0.08±0.01，新生儿 0.12±0.01，雄性成年 0.25±0.01，雌性成年 0.22±0.02；每组 4 只，p<0.001 胎儿和新生儿与雄性或雌性成年大鼠相比）。相比之下，胎儿和新生儿的 AT1R 蛋白表达明显高于成年大鼠（胎儿 0.64±0.09，新生儿 0.56±0.01，雄性成年 0.13±0.02，雌性成年 0.08±0.02；每组 4 只，p<0.001 胎儿和新生儿与雄性和雌性成年大鼠相比）。在肝脏中，胎儿和新生儿的 AT2R 蛋白也高于成年大鼠。有趣的是，胎肝的 AT1R 蛋白表达高于新生儿。在肾脏中，AT2R 表达随年龄增长而显著增加（胎儿 0.08±0.01，新生儿 0.19±0.02，雄性成年 0.49±0.04，雌性成年 0.90±0.10；每组 4 只，p<0.01-0.001）。另一方面，AT1R 表达在胎儿中高于新生儿和成年雄性大鼠。这项研究提供的数据与现有的教条相反，即 AT2R 表达在胎儿期较高，在成年期较低，这表明 AT2R 在成年动物中可能具有重要的功能作用，而 AT1R 在胎儿发育和/或生理学中起作用。
