Suzuki J, Matsubara H, Urakami M, Inada M
Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Circ Res. 1993 Sep;73(3):439-47. doi: 10.1161/01.res.73.3.439.
Two subtypes of angiotensin II (Ang II) receptors (AT1 and AT2) are distinguished by using the respective specific antagonists. In the present study, we report the regulation of cardiac AT1 type A (AT1A) receptor mRNA levels and the expression pattern of AT1 and AT2 receptors in the growth of the heart and the development and regression of cardiac hypertrophy. The ventricular AT1A mRNA level and the density of Ang II receptors at the neonatal period were significantly increased (3.5-fold and 2.5-fold, respectively) and then downregulated with maturation. The cardiac hypertrophy established in spontaneously hypertensive rats or two-kidney one-clip renovascular hypertensive rats resulted in substantial increases in ventricular AT1A mRNA levels (threefold) and Ang II receptor densities (twofold) as compared with those in respective control rats, whereas the receptor affinity was similar. The proportion of AT1 and AT2 subtypes in the specific Ang II binding in ventricular membranes prepared from normal adult rats was nearly equal. This proportion did not change significantly in the development of myocardial hypertrophy. The regression of cardiac hypertrophy by the normalization of elevated blood pressure completely reversed the increased levels of AT1A mRNA and the receptor density to the control level. Thus, AT1 and AT2 receptors are present in rat ventricular myocardium, and their expression is developmentally regulated and upregulated in response to hypertrophic change. Ang II action exerted through the increased number of Ang II receptors may contribute to the growth of the heart and thus to the maintenance of established hypertrophy as one of the hormones involved in hypertrophy development.
通过使用各自的特异性拮抗剂可区分出两种血管紧张素II（Ang II）受体亚型（AT1和AT2）。在本研究中，我们报告了心脏AT1A型（AT1A）受体mRNA水平的调节以及AT1和AT2受体在心脏生长、心脏肥大的发展和消退过程中的表达模式。新生期心室AT1A mRNA水平和Ang II受体密度显著增加（分别为3.5倍和2.5倍），然后随着成熟而下调。与各自的对照大鼠相比，自发性高血压大鼠或二肾一夹肾血管性高血压大鼠中建立的心脏肥大导致心室AT1A mRNA水平（三倍）和Ang II受体密度（两倍）大幅增加，而受体亲和力相似。正常成年大鼠心室膜中特异性Ang II结合中AT1和AT2亚型的比例几乎相等。在心肌肥大的发展过程中，这一比例没有显著变化。通过血压正常化使心脏肥大消退，可使AT1A mRNA水平和受体密度的升高完全逆转至对照水平。因此，AT1和AT2受体存在于大鼠心室心肌中，它们的表达受到发育调节，并在肥大变化时上调。通过增加Ang II受体数量发挥的Ang II作用可能有助于心脏生长，从而作为参与肥大发展的激素之一维持已建立的肥大。
