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(Hypertension. 1997;30:358.)
© 1997 American Heart Association, Inc.

Articles

Growth-Dependent Induction of Angiotensin II Type 2 Receptor in Rat Mesangial Cells

Masahisa Goto; Masashi Mukoyama; Shin-ichi Suga; Tsunekazu Matsumoto; Masayo Nakagawa; Rieko Ishibashi; Masato Kasahara; Akira Sugawara; Issei Tanaka; Kazuwa Nakao

From the Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Correspondence to Masashi Mukoyama, MD, PhD, Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan. E-mail muko{at}kuhp.kyoto-u.ac.jp

Abstract Angiotensin II acts on at least two receptor subtypes, AT₁ and AT₂. Although the physiological role of the AT₂ receptor is still poorly defined, it may be implicated in inhibition of cell growth, vasorelaxation, and apoptosis. In the present study, to investigate the role of the AT₂ receptor in the kidney and its implication in hypertensive states, we examined its expression using cultured mesangial cells (MC) from normotensive Wistar-Kyoto rats (WKY) and from stroke-prone spontaneously hypertensive rats (SHRSP). Receptor binding assays were performed using a nonselective ligand, [Sar¹,Ile⁸]angiotensin II, or AT₂-selective CGP42112A. Binding assays revealed that MC from WKY exhibited both AT₁ and AT₂ receptors, the ratio of which was confluence-dependent. In contrast, MC from SHRSP, whose proliferation activity was much higher than those from WKY, showed only the AT₁ subtype. In receptor binding and Northern blot analyses, expression of the AT₂ receptor of WKY-MC was low in the growing state but significantly induced upon confluence to become abundant in the postconfluent state, whereas that of SHRSP-MC was undetectable in either state. Gene expressions of AT_1A and AT_1B receptors were not significantly altered in either strain during the time in culture. These results indicate that the mesangial AT₂-receptor expression is growth-dependent and suggest a role in the inhibition of MC growth in WKY. Much lower expression of the AT₂ receptor in MC from SHRSP may suggest involvement in their higher proliferation activity and possibly in consequent renal disorders.

Key Words: receptors, angiotensin • angiotensin II • mesangium, glomerular • rats, inbred SHR

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