Vascular Biology – Hemodynamics – Hypertension
Kidney International (2001) 60, 722–731; doi:10.1046/j.1523-1755.2001.060002722.x
Hyperplastic vascular smooth muscle cells of the intrarenal arteries in angiotensin II type 1a receptor null mutant mice
Sachiko Inokuchi, Kenjiro Kimura, Takeshi Sugaya, Koiti Inokuchi, Kazuo Murakami and Tatsuo Sakai
Department of Anatomy, Juntendo University, School of Medicine, Tokyo; Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo; Institute of Applied Biochemistry, University of Tsukuba, Ibaragi; and Lead Generation Research Laboratories, Tanabe Seiyaku Co., Ltd., Kashima, Osaka; Third Department of Internal Medicine, Nippon Medical School, Tokyo; Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaragi; and Department of Anatomy, Juntendo University, School of Medicine, Tokyo, Japan
Correspondence: Dr Sachiko Inokuchi, Department of Anatomy, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: inokuchi@med.juntendo.ac.jp
Received 27 December 1999; Revised 19 January 2001; Accepted 12 March 2001.
Abstract
Hyperplastic vascular smooth muscle cells of the intrarenal arteries in angiotensin II type 1a receptor null mutant mice.
Background
Angiotensin II (Ang II), which contracts vascular smooth muscle cells (VSMCs), has been reported to regulate VSMC growth. Recently formed transgenic mice without angiotensinogen or Ang II receptors showed vascular alterations. However, it is still unclear how their VSMCs alter. We explored the role of Ang II via the Ang II type 1a receptor (AT1a) in VSMCs in vivo using AT1a null mutant mice.
Methods
We analyzed the ultrastructure of the intrarenal arteries in AT1a null mutant mice that were homozygous for a targeted disruption of AT1a receptor gene using light and electron microscopy.
Results
The structural changes of the intrarenal arteries in AT1a null mutant mice showed the wall thickening, which in the interlobar, arcuate, and proximal interlobular arteries consisted of two additional populations of VSMCs, on the luminal and abluminal sides of the media. The luminal overpopulation of smooth muscle cells (SMCs) was arranged in a longitudinal direction separated by increased interposed elastic laminae. The abluminal overpopulation of SMCs ran in circumferential directions separated from the main population. The cytological structure of VSMCs in AT1a null mutant mice was smaller in size, contained more organelles for protein synthesis and secretion than in control mice, and had poorly developed contractile apparatus.
Conclusions
The lack of AT1a signaling causes structural abnormalities in the renal vascular system and transforms the phenotype of VSMCs into cell proliferation, induces the escape of VSMCs from the circular mechanical integrity, and results in increased synthesis of extracellular matrices.
Keywords:
renal artery, hypertrophy, cell signaling, extracellular matrix, renin-angiotensin system, targeted gene deletion, intrarenal vascular structure
