This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Furukawa, Y. Articles by Sasayama, S. Search for Related Content PubMed PubMed Citation Articles by Furukawa, Y. Articles by Sasayama, S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CAPTOPRIL Medline Plus Health Information Heart Transplantation

(Circulation. 1996;93:333-339.)
© 1996 American Heart Association, Inc.

Articles

Angiotensin II Receptor Antagonist TCV-116 Reduces Graft Coronary Artery Disease and Preserves Graft Status in a Murine Model

A Comparative Study With Captopril

Yutaka Furukawa, MD; Akira Matsumori, MD; Toshiro Hirozane, MD; Shigetake Sasayama, MD

From the Third Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, Kyoto, Japan.

Correspondence to Akira Matsumori, MD, Third Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto 606, Japan.

Background Despite the current progress in immunosuppressive regimens, the incidence of graft coronary artery disease (CAD) after cardiac transplantation has not decreased. Recent study has revealed that angiotensin-converting enzyme (ACE) inhibition decreases CAD in rats; however, it is not clear whether this beneficial effect of ACE inhibition is due to a decrease in production of angiotensin II (Ang II) or inhibition of bradykinin degradation. To determine whether Ang II type 1 receptor (AT₁-R) blockade has an inhibitory effect on CAD, we evaluated the effects of TCV-116, an AT₁-R antagonist, in a murine model of cardiac transplantation.

Methods and Results Hearts of DBA/2 mice (H-2^d) were transplanted heterotopically to B10.D2 mice (H-2^d). Recipients were treated orally with TCV-116 (10 mg/kg per day), captopril (100 mg/kg per day), or vehicle only. Graft status, as assessed by palpation and inspection at laparotomy 70 days after transplantation, was preserved better in the TCV-116–treated group (P<.005) and in the captopril-treated group (P<.05) than in the vehicle-treated group. Intimal area in the graft coronary arterial wall decreased to 31% in the TCV-116–treated group (P<.001 versus vehicle-treated group) and to 34% (P<.005) in the captopril-treated group but was 45% in the vehicle-treated group. Fibrotic lesions of the left ventricle were less prominent in the TCV-116–treated (31%; P<.01 versus vehicle-treated group) and captopril-treated groups (33%; P<.05) than in the vehicle-treated group (54%).

Conclusions These findings show that AT₁-R blockade is at least as effective as ACE inhibition in management of chronic allograft rejection and suggest that Ang II may play an important role in chronic allograft rejection.

Key Words: transplantation • rejection • coronary disease • receptors • angiotensin

This article has been cited by other articles:

				A. Douillette, A. Bibeau-Poirier, S.-P. Gravel, J.-F. Clement, V. Chenard, P. Moreau, and M. J. Servant The Proinflammatory Actions of Angiotensin II Are Dependent on p65 Phosphorylation by the I{kappa}B Kinase Complex J. Biol. Chem., May 12, 2006; 281(19): 13275 - 13284. [Abstract] [Full Text] [PDF]

				J.-i. Suzuki, M. Ogawa, Y. M. Sagesaka, and M. Isobe Tea catechins attenuate ventricular remodeling and graft arterial diseases in murine cardiac allografts Cardiovasc Res, January 1, 2006; 69(1): 272 - 279. [Abstract] [Full Text] [PDF]

				Y Inokuchi, T Morohashi, I Kawana, Y Nagashima, M Kihara, and S Umemura Amelioration of 2,4,6-trinitrobenzene sulphonic acid induced colitis in angiotensinogen gene knockout mice Gut, March 1, 2005; 54(3): 349 - 356. [Abstract] [Full Text] [PDF]

				Y. Furukawa, S. E Cole, R. V Shah, Y. Fukumoto, P. Libby, and R. N Mitchell Wild-type but not interferon-{gamma}-deficient T cells induce graft arterial disease in the absence of B cells Cardiovasc Res, August 1, 2004; 63(2): 347 - 356. [Abstract] [Full Text] [PDF]

				M. Yousufuddin, S. Haji, R. C. Starling, E. M. Tuzcu, N. B. Ratliff, D. J. Cook, A. Abdo, Y. Saad, S. S. Karnik, D. Wang, et al. Cardiac angiotensin II receptors as predictors of transplant coronary artery disease following heart transplantation Eur. Heart J., March 1, 2004; 25(5): 377 - 385. [Abstract] [Full Text] [PDF]

				T. Hattori, H. Shimokawa, M. Higashi, J. Hiroki, Y. Mukai, K. Kaibuchi, and A. Takeshita Long-Term Treatment With a Specific Rho-Kinase Inhibitor Suppresses Cardiac Allograft Vasculopathy in Mice Circ. Res., January 9, 2004; 94(1): 46 - 52. [Abstract] [Full Text] [PDF]

				J. Shao, M. Nangaku, T. Miyata, R. Inagi, K. Yamada, K. Kurokawa, and T. Fujita Imbalance of T-Cell Subsets in Angiotensin II-Infused Hypertensive Rats With Kidney Injury Hypertension, July 1, 2003; 42(1): 31 - 38. [Abstract] [Full Text] [PDF]

				M. NORIS, N. AZZOLLINI, A. PEZZOTTA, M. MISTER, A. BENIGNI, G. MARCHETTI, E. GAGLIARDINI, N. PERICO, and G. REMUZZI Combined Treatment with Mycophenolate Mofetil and an Angiotensin II Receptor Antagonist Fully Protects from Chronic Rejection in a Rat Model of Renal Allograft J. Am. Soc. Nephrol., September 1, 2001; 12(9): 1937 - 1946. [Abstract] [Full Text] [PDF]

				M. Sata, Z. Luo, and K. Walsh Fas Ligand Overexpression on Allograft Endothelium Inhibits Inflammatory Cell Infiltration and Transplant-Associated Intimal Hyperplasia J. Immunol., June 1, 2001; 166(11): 6964 - 6971. [Abstract] [Full Text] [PDF]

				M. Kawauchi, J.-i. Suzuki, R. Morishita, Y. Wada, A. Izawa, N. Tomita, J. Amano, Y. Kaneda, T. Ogihara, S. Takamoto, et al. Gene Therapy for Attenuating Cardiac Allograft Arteriopathy Using Ex Vivo E2F Decoy Transfection by HVJ-AVE-Liposome Method in Mice and Nonhuman Primates Circ. Res., November 24, 2000; 87(11): 1063 - 1068. [Abstract] [Full Text] [PDF]

				J.-i. Suzuki, M. Isobe, R. Morishita, T. Nishikawa, J. Amano, and Y. Kaneda Antisense Bcl-x oligonucleotide induces apoptosis and prevents arterial neointimal formation in murine cardiac allografts Cardiovasc Res, February 1, 2000; 45(3): 783 - 787. [Abstract] [Full Text] [PDF]

				P. E. Tummala, X.-L. Chen, C. L. Sundell, J. B. Laursen, C. P. Hammes, R. W. Alexander, D. G. Harrison, and R. M. Medford Angiotensin II Induces Vascular Cell Adhesion Molecule-1 Expression In Rat Vasculature : A Potential Link Between the Renin-Angiotensin System and Atherosclerosis Circulation, September 14, 1999; 100(11): 1223 - 1229. [Abstract] [Full Text] [PDF]

				T. Kita LOX-1, a Possible Clue to the Missing Link Between Hypertension and Atherogenesis Circ. Res., May 14, 1999; 84(9): 1113 - 1115. [Full Text] [PDF]

				X.-L. Chen, P. E. Tummala, M. T. Olbrych, R. W. Alexander, and R. M. Medford Angiotensin II Induces Monocyte Chemoattractant Protein-1 Gene Expression in Rat Vascular Smooth Muscle Cells Circ. Res., November 2, 1998; 83(9): 952 - 959. [Abstract] [Full Text] [PDF]

				T. Shioi, A. Matsumori, and S. Sasayama Persistent Expression of Cytokine in the Chronic Stage of Viral Myocarditis in Mice Circulation, December 1, 1996; 94(11): 2930 - 2937. [Abstract] [Full Text]