Circulation Research, Vol 73, 439-447, Copyright © 1993 by American Heart Association

ARTICLES

Rat angiotensin II (type 1A) receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy

J Suzuki, H Matsubara, M Urakami and M Inada
Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan.

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.

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				S. Murasawa, H. Matsubara, K. Kizima, K. Maruyama, Y. Mori, and M. Inada Glucocorticoids Regulate V1a Vasopressin Receptor Expression by Increasing mRNA Stability in Vascular Smooth Muscle Cells Hypertension, October 1, 1995; 26(4): 665 - 669. [Abstract] [Full Text]

				T. Ichiki and T. Inagami Transcriptional Regulation of the Mouse Angiotensin II Type 2 Receptor Gene Hypertension, April 1, 1995; 25(4): 720 - 725. [Abstract] [Full Text]

				H. Schunkert, J.-i. Sadoshima, T. Cornelius, Y. Kagaya, E. O. Weinberg, S. Izumo, G. Riegger, and B. H. Lorell Angiotensin II–Induced Growth Responses in Isolated Adult Rat Hearts : Evidence for Load-Independent Induction of Cardiac Protein Synthesis by Angiotensin II Circ. Res., March 1, 1995; 76(3): 489 - 497. [Abstract] [Full Text]

				V. Regitz-Zagrosek, N. Friedel, A. Heymann, P. Bauer, M. Neuß, A. Rolfs, C. Steffen, A. Hildebrandt, R. Hetzer, and E. Fleck Regulation, Chamber Localization, and Subtype Distribution of Angiotensin II Receptors in Human Hearts Circulation, March 1, 1995; 91(5): 1461 - 1471. [Abstract] [Full Text]

				G. Bruckschlegel, S. R. Holmer, K. Jandeleit, D. Grimm, F. Muders, E. P. Kromer, G. A. J. Riegger, and H. Schunkert Blockade of the Renin-Angiotensin System in Cardiac Pressure-Overload Hypertrophy in Rats Hypertension, February 1, 1995; 25(2): 250 - 259. [Abstract] [Full Text]

				W. G. Thomas, Y. Brandenburger, D. J. Autelitano, T. Pham, H. Qian, and R. D. Hannan Adenoviral-Directed Expression of the Type 1A Angiotensin Receptor Promotes Cardiomyocyte Hypertrophy via Transactivation of the Epidermal Growth Factor Receptor Circ. Res., February 8, 2002; 90(2): 135 - 142. [Abstract] [Full Text] [PDF]