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| Angiotensin II receptor antagonist TCV-116 reduces graft coronary artery disease and preserves graft status in a murine model - A comparative study with captopril |
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| Author(s): Furukawa Y, Matsumori A, Hirozane T, Sasayama S |
| Source: CIRCULATION Volume: 93 Issue: 2 Pages: 333-339 Published: JAN 15 1996 |
| Times Cited: 60 References: 46 |
| Abstract: 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 (AT(1)-R) blockade has an inhibitory effect on CAD, we evaluated the effects of TCV-116, an, AT(1)-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 AT(1)-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.
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| Document Type: Article |
| Language: English |
Addresses:
1. KYOTO UNIV, FAC MED, DEPT INTERNAL MED, DIV 3, SAKYO KU, KYOTO 606, JAPAN |
| Publisher: AMER HEART ASSOC, 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 |
| Subject Category: Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease |
| IDS Number: TP779 |
| ISSN: 0009-7322 |
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